RESUMEN

This study explores the therapeutic benefits of tannic acid (TnA) in an experimental protocol of chronic hypermethioninemia in rats. Rats were categorized into four groups: Group I - control, Group II - TnA 30 mg/kg, Group III - methionine (Met) 0.2-0.4 g/kg + methionine sulfoxide (MS) 0.05-0.1 g/kg, Group IV - TnA/Met + MS. Saline was administered by subcutaneous pathway into groups I and II twice daily from postnatal day 6 (P6) to P28, whereas those in groups III and IV received Met + MS. From P28 to P35, groups II and IV received TnA orally. Animals from group III presented cognitive and memory impairment assessed through object recognition and Y-maze tests (p < 0.05). Elevated levels of reactive species, lipid peroxidation, and nitrites followed by a decline in sulfhydryl content, catalase activity, and superoxide dismutase activity were observed in animals treated with Met + MS (p < 0.05). However, TnA treatment reversed all these effects (p < 0.05). In group III, there was an increase in acetylcholinesterase activity and IL-6 levels, coupled with a reduction in Na+/K+-ATPase activity (p < 0.05). TnA was able to protect against these effects (p < 0.05). The gene expression of catalase, brain-derived neurotrophic factor, and nuclear factor erythroid 2-related factor 2 was decreased in the hippocampus and striatum from group III (p < 0.05). TnA reversed almost all of these alterations (p < 0.05). These findings suggest that TnA is a therapeutic target for patients with hypermethioninemia.

Asunto(s)

Errores Innatos del Metabolismo de los Aminoácidos , Taninos , Animales , Taninos/farmacología , Ratas , Errores Innatos del Metabolismo de los Aminoácidos/tratamiento farmacológico , Errores Innatos del Metabolismo de los Aminoácidos/metabolismo , Masculino , Ratas Wistar , Peroxidación de Lípido/efectos de los fármacos , Estrés Oxidativo/efectos de los fármacos , Factor Neurotrófico Derivado del Encéfalo/metabolismo , Factor Neurotrófico Derivado del Encéfalo/genética , ATPasa Intercambiadora de Sodio-Potasio/metabolismo , Glicina N-Metiltransferasa/deficiencia , Polifenoles

RESUMEN

Clinical evidence suggests that early malnutrition promotes symptoms related to psychiatric disorders later in life. Nevertheless, the molecular mechanisms underpinning nutritional injury induce depression remains unknown. The purpose of the present study was to evaluate whether perinatal protein restriction increases vulnerability to developing depressive-like behavior in adulthood by focusing on anhedonia, a core symptom of depression. To this, male adult Wistar rats submitted to a protein restriction schedule at perinatal age (PR-rats), were subjected to the sucrose preference test (SPT), the novel object recognition test (NORT), the forced swim test (FST), and the elevated plus maze (EPM), and compared to animals fed with a normoprotein diet. To investigate neurobiological substrates linked to early protein undernutrition-facilitated depressive-like behavior, we assessed the levels of brain-derived neurotrophic factor (BDNF) and its receptor TrkB in the nucleus accumbens (NAc), and evaluated the reversal of anhedonic-like behavior by infusing ANA-12. We found that early malnutrition decreased sucrose preference, impaired performance in the NORT and increased immobility time in the FST. Furthermore, perinatal protein-restriction-induced anhedonia correlated with increased BDNF and p-TrkB protein levels in the NAc, a core structure in the reward circuit linked with anhedonia. Finally, bilateral infusion of the TrkB antagonist ANA-12 into the NAc shell ameliorated a reduced sucrose preference in the PR-rats. Altogether, these findings revealed that protein restriction during pregnancy and lactation facilitates depressive-like behavior later in life and may increase the risk of developing anhedonia by altering BDNF-TrkB in the NAc shell.

Asunto(s)

Anhedonia , Factor Neurotrófico Derivado del Encéfalo , Núcleo Accumbens , Ratas Wistar , Receptor trkB , Transducción de Señal , Animales , Núcleo Accumbens/metabolismo , Núcleo Accumbens/efectos de los fármacos , Factor Neurotrófico Derivado del Encéfalo/metabolismo , Masculino , Anhedonia/fisiología , Ratas , Receptor trkB/metabolismo , Femenino , Transducción de Señal/fisiología , Transducción de Señal/efectos de los fármacos , Embarazo , Dieta con Restricción de Proteínas , Efectos Tardíos de la Exposición Prenatal/metabolismo , Depresión/metabolismo , Depresión/psicología , Azepinas , Benzamidas

RESUMEN

Glutamate is involved in fundamental functions, including neuronal plasticity and memory. Astrocytes are integral elements involved in synaptic function, and the GLT-1 transporter possesses a critical role in glutamate uptake. Here, we study the role of GLT-1, specifically located in astrocytes, in the consolidation, expression, reconsolidation and persistence of spatial object recognition memory in rats. Administration of dihydrokainic acid (DHK), a selective GLT-1 inhibitor, into the dorsal hippocampus around a weak training which only induces short-term memory, promotes long-term memory formation. This promotion is prevented by hippocampal administration of protein-synthesis translation inhibitor, blockade of Activity-regulated cytoskeleton-associated protein (Arc) translation or Brain-Derived Neurotrophic Factor (BDNF) action, which are plasticity related proteins necessary for memory consolidation. However, DHK around a strong training, which induces long-term memory, does not affect memory consolidation. Administration of DHK before the test session impairs the expression of long-term memory, and this effect is dependent of Arc translation. Furthermore, DHK impairs reconsolidation if applied before a reactivation session, and this effect is independent of Arc translation. These findings reveal specific consequences on spatial memory stages developed under hippocampal GLT-1 blockade, shedding light on the intricate molecular mechanisms, governed in part for the action of glia.

Asunto(s)

Astrocitos , Factor Neurotrófico Derivado del Encéfalo , Proteínas del Citoesqueleto , Ácido Glutámico , Hipocampo , Memoria Espacial , Animales , Hipocampo/efectos de los fármacos , Hipocampo/metabolismo , Hipocampo/fisiología , Astrocitos/efectos de los fármacos , Astrocitos/metabolismo , Memoria Espacial/efectos de los fármacos , Factor Neurotrófico Derivado del Encéfalo/metabolismo , Masculino , Ratas , Proteínas del Citoesqueleto/metabolismo , Proteínas del Citoesqueleto/genética , Ácido Glutámico/metabolismo , Proteínas del Tejido Nervioso/metabolismo , Proteínas del Tejido Nervioso/antagonistas & inhibidores , Proteínas del Tejido Nervioso/genética , Transportador 2 de Aminoácidos Excitadores/metabolismo , Transportador 2 de Aminoácidos Excitadores/antagonistas & inhibidores , Ratas Wistar , Ácido Kaínico/farmacología , Ácido Kaínico/análogos & derivados , Consolidación de la Memoria/efectos de los fármacos

RESUMEN

Rasmussen's encephalitis (RE) stands as a rare neurological disorder marked by progressive cerebral hemiatrophy and epilepsy resistant to medical treatment. Despite extensive study, the primary cause of RE remains elusive, while its histopathological features encompass cortical inflammation, neuronal degeneration, and gliosis. The underlying molecular mechanisms driving disease progression remain largely unexplored. In this case study, we present a patient with RE who underwent hemispherotomy and has remained seizure-free for over six months, experiencing gradual motor improvement. Furthermore, we conducted molecular analysis on the excised brain tissue, unveiling a decrease in the expression of cell-cycle-associated genes coupled with elevated levels of BDNF and TNF-α proteins. These findings suggest the potential involvement of cell cycle regulators in the progression of RE.

Asunto(s)

Encefalitis , Humanos , Encefalitis/genética , Encefalitis/patología , Encefalitis/metabolismo , Masculino , Proteínas de Ciclo Celular/genética , Proteínas de Ciclo Celular/metabolismo , Encéfalo/patología , Encéfalo/metabolismo , Factor Neurotrófico Derivado del Encéfalo/genética , Factor Neurotrófico Derivado del Encéfalo/metabolismo , Corteza Cerebral/patología , Corteza Cerebral/metabolismo , Femenino , Factor de Necrosis Tumoral alfa/metabolismo , Factor de Necrosis Tumoral alfa/genética , Ciclo Celular/genética

RESUMEN

Resistance exercise training (RET) is considered an excellent tool for preventing diseases with an inflammatory background. Its neuroprotective, antioxidant, and anti-inflammatory properties are responsible for positively modulating cholinergic and oxidative systems, promoting neurogenesis, and improving memory. However, the mechanisms behind these actions are largely unknown. In order to investigate the pathways related to these effects of exercise, we conducted a 12-week long-term exercise training protocol and used lipopolysaccharide (LPS) to induce damage to the cortex and hippocampus of male Wistar rats. The cholinergic system, oxidative stress, and histochemical parameters were analyzed in the cerebral cortex and hippocampus, and memory tests were also performed. It was observed that LPS: (1) caused memory loss in the novel object recognition (NOR) test; (2) increased the activity of acetylcholinesterase (AChE) and Iba1 protein density; (3) reduced the protein density of brain-derived neurotrophic factor (BDNF) and muscarinic acetylcholine receptor M1 (CHRM1); (4) elevated the levels of lipid peroxidation (TBARS) and reactive species (RS); and (5) caused inflammatory damage to the dentate gyrus. RET, on the other hand, was able to prevent all alterations induced by LPS, as well as increase per se the protein density of the alpha-7 nicotinic acetylcholine receptor (nAChRα7) and Nestin, and the levels of protein thiols (T-SH). Overall, our study elucidates some mechanisms that support resistance physical exercise as a valuable approach against LPS-induced neuroinflammation and memory loss.

Asunto(s)

Lipopolisacáridos , Trastornos de la Memoria , Enfermedades Neuroinflamatorias , Condicionamiento Físico Animal , Ratas Wistar , Animales , Masculino , Lipopolisacáridos/toxicidad , Condicionamiento Físico Animal/fisiología , Condicionamiento Físico Animal/métodos , Ratas , Enfermedades Neuroinflamatorias/metabolismo , Enfermedades Neuroinflamatorias/inducido químicamente , Trastornos de la Memoria/inducido químicamente , Trastornos de la Memoria/metabolismo , Hipocampo/metabolismo , Hipocampo/efectos de los fármacos , Estrés Oxidativo/efectos de los fármacos , Estrés Oxidativo/fisiología , Entrenamiento de Fuerza/métodos , Corteza Cerebral/metabolismo , Corteza Cerebral/efectos de los fármacos , Factor Neurotrófico Derivado del Encéfalo/metabolismo , Peroxidación de Lípido/efectos de los fármacos , Acetilcolinesterasa/metabolismo , Receptor Muscarínico M1/metabolismo

RESUMEN

This systematic review addresses the complex nature of Panic Disorder (PD), characterized by recurrent episodes of acute fear, with a focus on updating and consolidating knowledge regarding neurochemical, genetic, and epigenetic factors associated with PD. Utilizing the PRISMA methodology, 33 original peer-reviewed studies were identified, comprising 6 studies related to human neurochemicals, 10 related to human genetic or epigenetic alterations, and 17 animal studies. The review reveals patterns of altered expression in various biological systems, including neurotransmission, the Hypothalamic-Pituitary-Adrenal (HPA) axis, neuroplasticity, and genetic and epigenetic factors leading to neuroanatomical modifications. Noteworthy findings include lower receptor binding of GABAA and serotonin neurotransmitters in the amygdala. The involvement of orexin (ORX) neurons in the dorsomedial/perifornical region in triggering panic reactions is highlighted, with systemic ORX-1 receptor antagonists blocking panic responses. Elevated Interleukin 6 and leptin levels in PD patients suggest potential connections between stress-induced inflammatory changes and PD. Brain-derived neurotrophic factor (BDNF) and tyrosine receptor kinase B (TrkB) signaling are implicated in panic-like responses, particularly in the dorsal periaqueductal gray (dPAG), where BDNF's panicolytic-like effects operate through GABAA-dependent mechanisms. GABAergic neurons' inhibitory influence on dorsomedial and posterior hypothalamus nuclei is identified, potentially reducing the excitability of neurons involved in panic-like responses. The dorsomedial hypothalamus (DMH) is highlighted as a specific hypothalamic nucleus relevant to the genesis and maintenance of panic disorder. Altered brain lactate and glutamate concentrations, along with identified genetic polymorphisms linked to PD, further contribute to the intricate neurochemical landscape associated with the disorder. The review underscores the potential impact of neurochemical, genetic, and epigenetic factors on the development and expression of PD. The comprehensive insights provided by this systematic review contribute to advancing our understanding of the multifaceted nature of Panic Disorder and pave the way for targeted therapeutic strategies.

Asunto(s)

Sistema Hipotálamo-Hipofisario , Trastorno de Pánico , Humanos , Trastorno de Pánico/genética , Trastorno de Pánico/metabolismo , Animales , Sistema Hipotálamo-Hipofisario/metabolismo , Sistema Hipófiso-Suprarrenal/metabolismo , Orexinas/metabolismo , Orexinas/genética , Factor Neurotrófico Derivado del Encéfalo/genética , Factor Neurotrófico Derivado del Encéfalo/metabolismo , Epigénesis Genética

RESUMEN

Linalool-rich Rosewood oil (Aniba rosaeodora Ducke) is a natural compound widely used in perfumery industry. Evidence suggests that linalool exerts antidepressant and anxiolytic effects. Conversely, ethanol binge drinking (i.e., intermittent and episodic consumption) during adolescence elicits neurobehavioral alterations associated with brain damage. Here, we investigated whether linalool-rich Rosewood oil administration can improve the emotional and molecular impairments associated with ethanol binge-like exposure during adolescence in female rats. Rosewood oil was obtained by hydrodistillation and posteriorly analyzed. Adolescent female Wistar rats received four-cycles of ethanol binge-like pattern (3 g/kg/day, 3 days on/4 days off) and daily Rosewood oil (35 mg/kg, intranasally) for 28 days. Twenty-four hours after treatments, it was evaluated the impact of ethanol exposure and Rosewood oil treatment on the putative emotional impairments assessed on the splash and forced swimming tests, as well as the levels of brain-derived neurotrophic factor (BDNF), S100B, oxidative parameters, and inflammatory cytokines in prefrontal cortex and hippocampus. Results indicated that Rosewood oil intranasal administration mitigated emotional impairments induced by ethanol exposure accompanied by a marked increase in BDNF, S100B, glutathione (GSH), and antioxidant activity equivalent to Trolox (TEAC) levels in brain areas. Rosewood oil treatment also prevented the ethanol-induced increase of interleukin-1ß, interleukin-6, tumor necrosis factor α (TNF-α), and neurofilament light chain (NFL) levels. These findings provide the first evidence that Rosewood oil intranasal administration exerts protective effects against emotional and molecular impairments associated with adolescent ethanol binge-like exposure, possibly due to linalool actions triggering neurotrophic factors, rebalancing antioxidant status, and attenuating proinflammatory process.

Asunto(s)

Monoterpenos Acíclicos , Etanol , Aceites Volátiles , Ratas Wistar , Animales , Femenino , Aceites Volátiles/farmacología , Aceites Volátiles/aislamiento & purificación , Monoterpenos Acíclicos/farmacología , Ratas , Consumo Excesivo de Bebidas Alcohólicas/tratamiento farmacológico , Antioxidantes/farmacología , Estrés Oxidativo/efectos de los fármacos , Emociones/efectos de los fármacos , Conducta Animal/efectos de los fármacos , Hipocampo/efectos de los fármacos , Hipocampo/metabolismo , Citocinas/metabolismo , Factor Neurotrófico Derivado del Encéfalo/metabolismo , Corteza Prefrontal/efectos de los fármacos , Corteza Prefrontal/metabolismo

RESUMEN

The state of Maternal Protein Malnutrition (MPM) is associated with several deleterious effects, including inflammatory processes and dysregulation in oxidative balance, which can promote neurodegeneration. On the other hand, it is known that aerobic exercise can promote systemic health benefits, combating numerous chronic diseases. Therefore, we evaluate the effect of aerobic exercise training (AET) on indicators of mitochondrial bioenergetics, oxidative balance, endoplasmic reticulum stress, and neurotrophic factor in the prefrontal cortex of malnourished juvenile Wistar rats. Pregnant Wistar rats were fed with a diet containing 17% or 8% casein during pregnancy and lactation. At 30 days of life, male offspring were divided into 4 groups: Low-Protein Control (LS), Low-Protein Trained (LT), Normoprotein Control (NS), and Normoprotein Trained (NT). The trained groups performed an AET for 4 weeks, 5 days a week, 1 h a day per session. At 60 days of life, the animals were sacrificed and the skeletal muscle, and prefrontal cortex (PFC) were removed to evaluate the oxidative metabolism markers and gene expression of ATF-6, GRP78, PERK and BDNF. Our results showed that MPM impairs oxidative metabolism associated with higher oxidative and reticulum stress. However, AET restored the levels of indicators of mitochondrial bioenergetics, in addition to promoting resilience to cellular stress. AET at moderate intensity for 4 weeks in young Wistar rats can act as a non-pharmacological intervention in fighting against the deleterious effects of a protein-restricted maternal diet.

Asunto(s)

Factor Neurotrófico Derivado del Encéfalo , Mitocondrias , Estrés Oxidativo , Condicionamiento Físico Animal , Ratas Wistar , Animales , Femenino , Ratas , Mitocondrias/metabolismo , Embarazo , Masculino , Factor Neurotrófico Derivado del Encéfalo/metabolismo , Estrés del Retículo Endoplásmico , Biomarcadores/metabolismo , Corteza Prefrontal/metabolismo , Músculo Esquelético/metabolismo , Desnutrición/metabolismo , Efectos Tardíos de la Exposición Prenatal/metabolismo , Factor de Transcripción Activador 6/metabolismo

RESUMEN

Environmental contamination by pharmaceuticals from industrial waste and anthropogenic activities poses adverse health effects on non-target organisms. We evaluated the neurobehavioral and biochemical responses accompanying exposure to ecological relevant concentrations of atenolol (0, 0.1, 1.0, and 10 µg/L) for seven uninterrupted days in adult zebrafish (Danio rerio). Atenolol-exposed fish exhibited anxiety-like behavior, characterized by significant bottom-dwelling with marked reduction in vertical exploration. Atenolol-exposed fish exhibited marked increase in the duration and frequency of aggressive events without altering their preference for conspecifics. Biochemical data using brain samples indicated that atenolol disrupted antioxidant enzyme activities and induced oxidative stress. Exposure to atenolol markedly decreased ATP and AMP hydrolysis without affecting ADP hydrolysis and acetylcholinesterase (AChE) activity. Atenolol significantly upregulated tryptophan hydroxylase 1 (tph1) mRNA expression but downregulated brain-derived neurotrophic factor (bdnf) mRNA. Collectively, waterborne atenolol elicits aggressive and anxiety-like responses in adult zebrafish, accompanied by oxidative stress, reduced nucleotide hydrolysis, altered tph1 and bdnf mRNA expression, which may impact the survival and health of fish in aquatic environment.

Asunto(s)

Atenolol , Conducta Animal , Estrés Oxidativo , Contaminantes Químicos del Agua , Pez Cebra , Animales , Atenolol/farmacología , Contaminantes Químicos del Agua/toxicidad , Estrés Oxidativo/efectos de los fármacos , Conducta Animal/efectos de los fármacos , Triptófano Hidroxilasa/metabolismo , Triptófano Hidroxilasa/genética , Factor Neurotrófico Derivado del Encéfalo/metabolismo

RESUMEN

Previous studies from our laboratory have shown sex differences in the behavioral, molecular, and neurochemical manifestations of morphine withdrawal and they were related to an increased sensitivity to morphine effects in males. In addition, we observed an interaction between the GABAergic and opioid systems that could also be sex-dependent. Baclofen, a GABAB receptor agonist, prevented the somatic expression and the molecular and neurochemical changes induced by morphine withdrawal syndrome in mice. On the contrary, little is known about baclofen effects in the rewarding properties of morphine in male and female mice. The present study aimed to explore the effect of baclofen (1, 2 and 3 mg/kg, i.p.) pretreatment in the rewarding effects induced by morphine (7 mg/kg, s.c.) and its effect on c-Fos and brain-derived neurotrophic factor (BDNF) expression induced by the rewarding properties of morphine in prepubertal male and female mice. Baclofen (2 mg/kg) pretreatment prevented the rewarding effects of morphine only in male mice, while baclofen (3 mg/kg) reduced these effects in both sexes. Moreover, the rewarding effects of morphine were associated with a decrease of BDNF and c-Fos expression cingulate cortex, nucleus accumbens shell, cornu ammonis 1 (CA1), and cornu ammonis 3 (CA3) areas of the hippocampus only in male mice. In addition, baclofen pretreatment prevented these changes in BDNF, but not in c-Fos expression. In conclusion, our results show that GABAB receptors have a regulatory role in the rewarding effects of morphine that could be of interest for a potential future therapeutic application in opioid use disorders.

Asunto(s)

Baclofeno , Factor Neurotrófico Derivado del Encéfalo , Morfina , Proteínas Proto-Oncogénicas c-fos , Recompensa , Animales , Baclofeno/farmacología , Masculino , Femenino , Morfina/farmacología , Ratones , Factor Neurotrófico Derivado del Encéfalo/metabolismo , Proteínas Proto-Oncogénicas c-fos/metabolismo , Agonistas de Receptores GABA-B/farmacología , Caracteres Sexuales , Conducta Animal/efectos de los fármacos , Factores Sexuales

RESUMEN

Aging compromises brain function leading to cognitive decline. A cyclic ketogenic diet (KD) improves memory in aged mice after long-term administration; however, short-term effects later in life and the molecular mechanisms that govern such changes remain unclear. Here, we explore the impact of a short-term KD treatment starting at elderly stage on brain function of aged mice. Behavioral testing and long-term potentiation (LTP) recordings reveal that KD improves working memory and hippocampal LTP. Furthermore, the synaptosome proteome of aged mice fed a KD long-term evidence changes predominantly at the presynaptic compartment associated to the protein kinase A (PKA) signaling pathway. These findings were corroborated in vivo by western blot analysis, with high BDNF abundance and PKA substrate phosphorylation. Overall, we show that a KD modifies brain function even when it is administered later in life and recapitulates molecular features of long-term administration, including the PKA signaling pathway, thus promoting synaptic plasticity at advanced age.

Asunto(s)

Envejecimiento , Proteínas Quinasas Dependientes de AMP Cíclico , Dieta Cetogénica , Potenciación a Largo Plazo , Memoria , Proteoma , Transducción de Señal , Animales , Proteínas Quinasas Dependientes de AMP Cíclico/metabolismo , Envejecimiento/fisiología , Envejecimiento/metabolismo , Dieta Cetogénica/métodos , Proteoma/metabolismo , Ratones , Masculino , Memoria/fisiología , Potenciación a Largo Plazo/fisiología , Ratones Endogámicos C57BL , Hipocampo/metabolismo , Sinapsis/metabolismo , Factor Neurotrófico Derivado del Encéfalo/metabolismo , Plasticidad Neuronal/fisiología , Fosforilación

RESUMEN

This study aimed to compare the effects of High-Intensity Interval Training (HIIT) performed in a single session(1xHIIT) versus three daily sessions (3xHIIT) on fitness level and behavior of aged rats. Eighteen-month-old Wistar rats were assigned to Untrained (UN), 1xHIIT, or 3xHIIT (n = 12/group). Both groups, 1xHIIT and 3xHIIT, performed 15 min of a treadmill running HIIT protocol during 8 weeks. 1xHIIT protocol consisted of a single daily session of 15 min, while the 3xHIIT performed three daily sessions of 5 min with a 4 h interval between the sessions. Morris Water Maze (MWM) task was used to evaluate spatial learning and memory. Splash test, Forced Swim test, and Elevated Plus Maze task (EPM) were used to evaluate anhedonic, depressive-like, and anxious behaviors, respectively. Rats were euthanized, and the hippocampus was harvested for western blot analyses (CaMKII and BDNF). Both HIIT protocols improved VO2max and spatial memory. Notably, only the 3xHIIT protocol attenuated anxious and depressive-like behaviors. Western blot analyses of the hippocampus revealed that both HIIT protocols increased BDNF levels. BDNF levels were higher in the 3xHIIT when compared with 1xHIIT group, and we observed increasement of the CamKII levels just in the 3x HIIT group. Therefore, this study provides evidence indicating that accumulated HIIT sessions is more effective than traditional daily HIIT sessions in improving fitness level, cognitive function, memory, inhibiting the development of mood disorders, and enhancing BDNF and CaMKII levels in the hippocampus of aged rats.

Asunto(s)

Envejecimiento , Ansiedad , Factor Neurotrófico Derivado del Encéfalo , Depresión , Entrenamiento de Intervalos de Alta Intensidad , Hipocampo , Ratas Wistar , Animales , Hipocampo/metabolismo , Ratas , Depresión/metabolismo , Depresión/terapia , Depresión/fisiopatología , Envejecimiento/fisiología , Envejecimiento/metabolismo , Ansiedad/metabolismo , Ansiedad/terapia , Ansiedad/fisiopatología , Entrenamiento de Intervalos de Alta Intensidad/métodos , Masculino , Factor Neurotrófico Derivado del Encéfalo/metabolismo , Cognición/fisiología , Proteína Quinasa Tipo 2 Dependiente de Calcio Calmodulina/metabolismo , Aprendizaje por Laberinto/fisiología , Condicionamiento Físico Animal/fisiología , Memoria Espacial/fisiología

RESUMEN

The CACNA1C gene encodes the alpha-1c subunit of the Cav1.2 calcium channel, a regulator of neuronal calcium influx involved in neurotransmitter release and synaptic plasticity. Genetic data show a role for CACNA1C in depressive symptoms underlying different psychiatric diagnoses. However, the mechanisms involved still require further exploration. This study aimed to investigate sex and region-specific changes in the Cacna1c gene and behavioral outcomes in mice exposed to chronic stress. Moreover, we evaluated the Nuclear factor of activated T-cells 5 (Nfat5) and the Brain-derived neurotrophic factor (Bdnf) as potential upstream and downstream Cacna1c targets and their correlation in stressed mice and humans with depression. Male and female Swiss mice were exposed to chronic unpredictable stress (CUS) for 21 days. Animal-integrated emotionality was assessed using the sucrose splash test, the tail suspension, the open-field test, and the elevated-plus-maze. Gene expression analysis was performed in the amygdala, prefrontal cortex, and hippocampus. Human data for in silico analysis was obtained from the Gene Expression Omnibus. CUS-induced impairment in integrated emotional regulation was observed in males. Gene expression analysis showed decreased levels of Cacna1c and Nfat5 and increased levels of Bdnf transcripts in the amygdala of stressed male mice. In contrast, there were no major changes in behavioral responses or gene expression in female mice after stress. The expression of the three genes was significantly correlated in the amygdala of mice and humans. The strong and positive correlation between Canac1c and Nfat5 suggests a potential role for this transcription factor in Canac1c expression. These changes could impact amygdala reactivity and emotional responses, making them a potential target for psychiatric intervention.

Asunto(s)

Amígdala del Cerebelo , Factor Neurotrófico Derivado del Encéfalo , Canales de Calcio Tipo L , Estrés Psicológico , Animales , Factor Neurotrófico Derivado del Encéfalo/metabolismo , Factor Neurotrófico Derivado del Encéfalo/genética , Canales de Calcio Tipo L/metabolismo , Canales de Calcio Tipo L/genética , Estrés Psicológico/metabolismo , Masculino , Femenino , Ratones , Amígdala del Cerebelo/metabolismo , Humanos , Modelos Animales de Enfermedad , Conducta Animal/fisiología , Corteza Prefrontal/metabolismo , Hipocampo/metabolismo , Adulto , Expresión Génica , Depresión/metabolismo , Depresión/fisiopatología

RESUMEN

OBJECTIVE: It has been previously shown that brain-derived neurotrophic factor is linked with various types of cancer. Brain-derived neurotrophic factor is found to be highly expressed in multiple human cancers and associated with tumor growth, invasion, and metastasis. Adipokinetic hormones are functionally related to the vertebrate glucagon, as they have similar functionalities that manage the nutrient-dependent secretion of these two hormones. Migrasomes are new organelles that contain numerous small vesicles, which aid in transmitting signals between the migrating cells. Therefore, the aim of this study was to investigate the effects of Anax imperator adipokinetic hormone on brain-derived neurotrophic factor expression and ultrastructure of cells in the C6 glioma cell line. METHODS: The rat C6 glioma cells were treated with concentrations of 5 and 10 Anax imperator adipokinetic hormone for 24 h. The effects of the Anax imperator adipokinetic hormone on the migrasome formation and brain-derived neurotrophic factor expression were analyzed using immunocytochemistry and transmission electron microscope. RESULTS: The rat C6 glioma cells of the 5 and 10 µM Anax imperator adipokinetic hormone groups showed significantly high expressions of brain-derived neurotrophic factor and migrasomes numbers, compared with the control group. CONCLUSION: A positive correlation was found between the brain-derived neurotrophic factor expression level and the formation of migrasome, which indicates that the increased expression of brain-derived neurotrophic factor and the number of migrasomes may be involved to metastasis of the rat C6 glioma cell line induced by the Anax imperator adipokinetic hormone. Therefore, the expression of brain-derived neurotrophic factor and migrasome formation may be promising targets for preventing tumor proliferation, invasion, and metastasis in glioma.

Asunto(s)

Factor Neurotrófico Derivado del Encéfalo , Glioma , Oligopéptidos , Ácido Pirrolidona Carboxílico , Glioma/metabolismo , Glioma/patología , Animales , Factor Neurotrófico Derivado del Encéfalo/metabolismo , Ratas , Línea Celular Tumoral , Ácido Pirrolidona Carboxílico/análogos & derivados , Ácido Pirrolidona Carboxílico/metabolismo , Oligopéptidos/farmacología , Hormonas de Insectos/metabolismo , Movimiento Celular/efectos de los fármacos , Inmunohistoquímica , Neoplasias Encefálicas/metabolismo , Neoplasias Encefálicas/patología , Orgánulos/metabolismo , Orgánulos/efectos de los fármacos , Orgánulos/ultraestructura

RESUMEN

Stroke is one of the leading causes of disability worldwide, where the Hippocampus (HPC) is affected. HPC organizes memory, which is a cognitive domain compromised after a stroke, where cerebrolysin (CBL) and Nicotinamide (NAM) have been recognized as potentially therapeutic. In this study, we aimed to evaluate the efficacy of a combined administration of CBL and NAM in a rat stroke model. Male Sprague-Dawley rats (n = 36) were divided into four groups: saline (pMCAO - Saline), CBL (pMCAO + CBL), NAM (pMCAO + NAM), and experimental (pMCAO + CBL-NAM) (n = 9 per group). A permanent middle cerebral artery occlusion (pMCAO) was induced through electrocauterization of the middle cerebral artery, followed by the administration of CBL (2.5 ml/kg), NAM (500 mg/kg) or combined immediately after skin suture, as well as at 24, 48, and 72 h post-surgery. The rats were evaluated in the novel object recognition test; hippocampal infarct area measurement; reconstruction of neurons from CA1 for Sholl analysis; and, measurement of brain-derived neurotrophic factor (BDNF) levels near the infarct zone. Our findings revealed that the administration of CBL or NAM induced infarct reduction, improved cognition, and increased BDNF levels. Moreover, a combination of CBL and NAM increased dendritic intersection in CA1 pyramidal neurons. Thus, the combined administration of CBL and NAM can promote cognitive recovery after a stroke, with infarct reduction, cytoarchitectural changes in HPC CA1 neurons, and BDNF increase. Our findings suggest that this combination therapy could be a promising intervention strategy for stroke.

Asunto(s)

Aminoácidos , Cognición , Hipocampo , Infarto de la Arteria Cerebral Media , Neuronas , Fármacos Neuroprotectores , Niacinamida , Ratas Sprague-Dawley , Animales , Masculino , Hipocampo/efectos de los fármacos , Hipocampo/patología , Hipocampo/metabolismo , Aminoácidos/farmacología , Aminoácidos/administración & dosificación , Infarto de la Arteria Cerebral Media/tratamiento farmacológico , Infarto de la Arteria Cerebral Media/patología , Niacinamida/farmacología , Niacinamida/administración & dosificación , Cognición/efectos de los fármacos , Neuronas/efectos de los fármacos , Neuronas/patología , Fármacos Neuroprotectores/farmacología , Fármacos Neuroprotectores/administración & dosificación , Ratas , Factor Neurotrófico Derivado del Encéfalo/metabolismo , Factor Neurotrófico Derivado del Encéfalo/administración & dosificación , Recuperación de la Función/efectos de los fármacos , Recuperación de la Función/fisiología , Quimioterapia Combinada , Modelos Animales de Enfermedad

RESUMEN

MicroRNAs can interfere with protein function by suppressing their messenger RNA translation or the synthesis of its related factors. The function of brain-derived neurotrophic factor (BDNF) is essential to the proper formation and function of the nervous system and is seen to be regulated by many microRNAs. However, understanding how microRNAs influence BDNF actions within cells requires a wider comprehension of their integrative regulatory mechanisms. Aim: In this literature review, we have synthesized the evidence of microRNA regulation on BDNF in cells and tissues, and provided an analytical discussion about direct and indirect mechanisms that appeared to be involved in BDNF regulation by microRNAs. Methods: Searches were conducted on PubMed.gov using the terms "BDNF" AND "MicroRNA" and "brain-derived neurotrophic factor" AND "MicroRNA", updated on 1 September 2023. Papers without open access were requested from the authors. One hundred and seventy-one papers were included for review and discussion. Results and Discussion: The local regulation of BDNF by microRNAs involves a complex interaction between a series of microRNAs with target proteins that can either inhibit or enhance BDNF expression, at the core of cell metabolism. Therefore, understanding this homeostatic balance provides resources for the future development of vector-delivery-based therapies for the neuroprotective effects of BDNF.

Asunto(s)

Factor Neurotrófico Derivado del Encéfalo , MicroARNs , Factor Neurotrófico Derivado del Encéfalo/metabolismo , Factor Neurotrófico Derivado del Encéfalo/genética , MicroARNs/genética , MicroARNs/metabolismo , Humanos , Animales , Regulación de la Expresión Génica

RESUMEN

INTRODUCTION: The excessive fat accumulation in obesity, resulting from an unbalanced diet, can lead to metabolic and neurological disorders and increase the risk of developing anxiety and depression. AIM: Assess the impact of dietary intervention (DI) on the serotonergic system, brain-derived neurotrophic factor (BDNF) expression and behaviors of obese mice. METHODS: Male C57BL/6 mice, 5 weeks old, received a high-fat diet (HFD) for 10 weeks for the induction of obesity. After this period, for 8 weeks, half of these animals received a control diet (CD), group obese (OB) + control diet (OB + CD, n = 10), and another half continued being fed HFD, group obese + HFD (OB + HFD, n = 10). At the end of the eighth week of intervention, behavioral tests were performed (sucrose preference test, open field, novel object recognition, elevated plus maze and tail suspension). Body weight and food intake were assessed weekly. Visceral adiposity, the hippocampal and hypothalamic protein expression of BDNF, 5-HT1A (5-HT1A serotonin receptor) and TPH2 (key enzyme in serotonin synthesis), were evaluated after euthanasia. RESULTS: The dietary intervention involved changing from a HFD to a CD over an 8-week period, effectively reduced body weight gain, adiposity, and anhedonia-like behavior. In the OB + HFD group, we saw a lower sucrose preference and shorter traveled distance in the open field, along with increased pro-BDNF expression in the hypothalamus compared to the OB + CD mice. However, the levels of TPH2 and 5-HT1A remained unchanged. CONCLUSION: The HFD model induced both obesity and anhedonia, but the dietary intervention successfully improved these conditions.

Asunto(s)

Adiposidad , Anhedonia , Peso Corporal , Factor Neurotrófico Derivado del Encéfalo , Dieta Alta en Grasa , Ratones Endogámicos C57BL , Obesidad , Serotonina , Animales , Factor Neurotrófico Derivado del Encéfalo/metabolismo , Masculino , Anhedonia/fisiología , Serotonina/metabolismo , Obesidad/metabolismo , Dieta Alta en Grasa/efectos adversos , Adiposidad/fisiología , Ratones , Peso Corporal/fisiología , Ratones Obesos , Hipocampo/metabolismo , Receptor de Serotonina 5-HT1A/metabolismo , Triptófano Hidroxilasa/metabolismo , Conducta Animal/fisiología , Hipotálamo/metabolismo , Patrones Dietéticos

RESUMEN

Recent evidence has supported a pathogenic role for neuroinflammation in Parkinson's disease (PD). Inflammatory response has been associated with symptoms and subtypes of PD. However, it is unclear whether immune changes are involved in the initial pathogenesis of PD, leading to the non-motor symptoms (NMS) observed in its prodromal stage. The current study aimed to characterize the behavioral and cognitive changes in a toxin-induced model of prodromal PD-like syndrome. We also sought to investigate the role of neuroinflammation in prodromal PD-related NMS. Male mice were subjected to bilateral intranasal infusion with 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) or saline (control group), followed by comprehensive behavioral, pathological and neurochemical analysis. Intranasal MPTP infusion was able to cause the loss of dopaminergic neurons in the substantia nigra (SN). In parallel, it induced impairment in olfactory discrimination and social memory consolidation, compulsive and anxiety-like behaviors, but did not influence motor performance. Iba-1 and GFAP expressions were increased in the SN, suggesting an activated state of microglia and astrocytes. Consistent with this, MPTP mice had increased levels of IL-10 and IL-17A, and decreased levels of BDNF and TrkA mRNA in the SN. The striatum showed increased IL-17A, BDNF, and NFG levels compared to control mice. In conclusion, neuroinflammation may play an important role in the early stage of experimental PD-like syndrome, leading to cognitive and behavioral changes. Our results also indicate that intranasal administration of MPTP may represent a valuable mouse model for prodromal PD.

Asunto(s)

Modelos Animales de Enfermedad , Ratones Endogámicos C57BL , Síntomas Prodrómicos , Sustancia Negra , Animales , Masculino , Sustancia Negra/metabolismo , Sustancia Negra/patología , Sustancia Negra/efectos de los fármacos , Neuronas Dopaminérgicas/patología , Neuronas Dopaminérgicas/metabolismo , Neuronas Dopaminérgicas/efectos de los fármacos , Enfermedades Neuroinflamatorias/patología , Cuerpo Estriado/metabolismo , Cuerpo Estriado/efectos de los fármacos , Cuerpo Estriado/patología , Ratones , Microglía/metabolismo , Microglía/patología , Inflamación/inducido químicamente , Inflamación/metabolismo , Inflamación/patología , Factor Neurotrófico Derivado del Encéfalo/metabolismo , Ansiedad/etiología , 1-Metil-4-fenil-1,2,3,6-Tetrahidropiridina/farmacología

RESUMEN

The benefits of physical exercise (PE) on memory consolidation have been well-documented in both healthy and memory-impaired animals. However, the underlying mechanisms through which PE exerts these effects are still unclear. In this study, we aimed to investigate the role of hippocampal protein synthesis in memory modulation by acute PE in rats. After novel object recognition (NOR) training, rats were subjected to a 30-min moderate-intensity acute PE on the treadmill, while control animals did not undergo any procedures. Using anisomycin (ANI) and rapamycin (RAPA), compounds that inhibit protein synthesis through different mechanisms, we manipulated protein synthesis in the CA1 region of the hippocampus to examine its contribution to memory consolidation. Memory was assessed on days 1, 7, and 14 post-training. Our results showed that inhibiting protein synthesis by ANI or RAPA impaired NOR memory consolidation in control animals. However, acute PE prevented this impairment without affecting memory persistence. We also evaluated brain-derived neurotrophic factor (BDNF) levels after acute PE at 0.5h, 2h, and 12h afterward and found no differences in levels compared to animals that did not engage in acute PE or were only habituated to the treadmill. Therefore, our findings suggest that acute PE could serve as a non-pharmacological intervention to enhance memory consolidation and prevent memory loss in conditions associated with hippocampal protein synthesis inhibition. This mechanism appears not to depend on BDNF synthesis in the early hours after exercise.

Asunto(s)

Amnesia , Anisomicina , Factor Neurotrófico Derivado del Encéfalo , Hipocampo , Condicionamiento Físico Animal , Ratas Wistar , Animales , Masculino , Condicionamiento Físico Animal/fisiología , Ratas , Hipocampo/metabolismo , Hipocampo/efectos de los fármacos , Anisomicina/farmacología , Factor Neurotrófico Derivado del Encéfalo/metabolismo , Factor Neurotrófico Derivado del Encéfalo/biosíntesis , Amnesia/metabolismo , Amnesia/prevención & control , Inhibidores de la Síntesis de la Proteína/farmacología , Sirolimus/farmacología , Biosíntesis de Proteínas/efectos de los fármacos , Biosíntesis de Proteínas/fisiología , Consolidación de la Memoria/efectos de los fármacos , Consolidación de la Memoria/fisiología , Reconocimiento en Psicología/efectos de los fármacos , Reconocimiento en Psicología/fisiología

RESUMEN

Orofacial nerve injuries may result in temporary or long-term loss of sensory function and decreased quality of life in patients. B vitamins are required for DNA synthesis and the repair and maintenance of phospholipids. In particular, vitamins B1, B6, and B12 are essential for neuronal function. Deficiency in vitamin B complex (VBC) has been linked to increased oxidative stress, inflammation and demyelination. Photobiomodulation (PBM) has antioxidant activity and is neuroprotective. In addition, a growing literature attests to the positive effects of PBM on nerve repair. To assess the effect of PBM and VBC on regenerative process we evaluated the expression of brain-derived neurotrophic factor (BDNF), nerve growth factor (NGF), myelin basic protein (MBP), laminin and neurofilaments (NFs) using Western blotting to identify regenerative pattern after chronic constriction injury of the infraorbital nerve (CCI IoN) treated by PBM, VBC or its combination. After CCI IoN, the rats were divided into six groups naive, sham, injured (CCI IoN), treated with photobiomodulation (904 nm, 6.23 J/cm2, CCI IoN + PBM), treated with VBC (containing B1, B6 and B12) 5 times, CCI IoN + VBC) and treated with PBM and VBC (CCI IoN + VBC + PBM). The treatments could revert low expression of BDNF, MBP and laminin. Also reverted the higher expression of neurofilaments and enhanced expression of NGF. PBM and VBC could accelerate injured infraorbital nerve repair in rats through reducing the expression of neurofilaments, increasing the expression of BDNF, laminin and MBP and overexpressing NGF. These data support the notion that the use of PBM and VBC may help in the treatment of nerve injuries. This finding has potential clinical applications.

Asunto(s)

Factor Neurotrófico Derivado del Encéfalo , Modelos Animales de Enfermedad , Terapia por Luz de Baja Intensidad , Factor de Crecimiento Nervioso , Regeneración Nerviosa , Complejo Vitamínico B , Animales , Ratas , Regeneración Nerviosa/efectos de la radiación , Terapia por Luz de Baja Intensidad/métodos , Factor Neurotrófico Derivado del Encéfalo/metabolismo , Factor de Crecimiento Nervioso/metabolismo , Masculino , Laminina/metabolismo , Traumatismos del Nervio Facial/radioterapia , Traumatismos del Nervio Facial/terapia , Ratas Wistar , Proteína Básica de Mielina/metabolismo