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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.
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Encefalite , Humanos , Encefalite/genética , Encefalite/patologia , Encefalite/metabolismo , Masculino , Proteínas de Ciclo Celular/genética , Proteínas de Ciclo Celular/metabolismo , Encéfalo/patologia , Encéfalo/metabolismo , Fator Neurotrófico Derivado do Encéfalo/genética , Fator Neurotrófico Derivado do Encéfalo/metabolismo , Córtex Cerebral/patologia , Córtex Cerebral/metabolismo , Feminino , Fator de Necrose Tumoral alfa/metabolismo , Fator de Necrose Tumoral alfa/genética , Ciclo Celular/genéticaRESUMO
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.
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Atenolol , Comportamento Animal , Estresse Oxidativo , Poluentes Químicos da Água , Peixe-Zebra , Animais , Atenolol/farmacologia , Poluentes Químicos da Água/toxicidade , Estresse Oxidativo/efeitos dos fármacos , Comportamento Animal/efeitos dos fármacos , Triptofano Hidroxilase/metabolismo , Triptofano Hidroxilase/genética , Fator Neurotrófico Derivado do Encéfalo/metabolismoRESUMO
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.
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Envelhecimento , Proteínas Quinases Dependentes de AMP Cíclico , Dieta Cetogênica , Potenciação de Longa Duração , Memória , Proteoma , Transdução de Sinais , Animais , Proteínas Quinases Dependentes de AMP Cíclico/metabolismo , Envelhecimento/fisiologia , Envelhecimento/metabolismo , Dieta Cetogênica/métodos , Proteoma/metabolismo , Camundongos , Masculino , Memória/fisiologia , Potenciação de Longa Duração/fisiologia , Camundongos Endogâmicos C57BL , Hipocampo/metabolismo , Sinapses/metabolismo , Fator Neurotrófico Derivado do Encéfalo/metabolismo , Plasticidade Neuronal/fisiologia , FosforilaçãoRESUMO
Neurotrophic keratopathy is an uncommon degenerative corneal disorder characterized by compromised corneal sensory innervation resulting in the formation of epithelial defects and nonhealing corneal ulcers. Various treatment modalities are available to stabilize disease progression, improve patient well-being, and prevent vision loss. For eligible patients, medical and surgical reinnervation have emerged as pioneering therapies, holding promise for better management. We present a comprehensive review of the disorder, providing an update relevant to ophthalmologists on pathogenesis, diagnosis, treatment options, and novel therapies targeting pathophysiological pathways.
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Córnea , Humanos , Córnea/inervação , Doenças da Córnea/terapia , Doenças da Córnea/diagnóstico , Doenças da Córnea/fisiopatologia , Doenças da Córnea/etiologiaRESUMO
Fibromyalgia (FM) is a painful chronic condition that significantly impacts the quality of life, posing challenges for clinical management. Given the difficulty of understanding the pathophysiology and finding new therapeutics, this study explored the effects of a medicinal plant, E. brasiliensis, in an FM model induced by reserpine in Swiss mice. Animals were treated with saline 0.9% (vehicle), duloxetine 10 mg/kg (positive control), or hydroalcoholic extract of E. brasiliensis leaves 300 mg/kg (HEEb). Nociceptive parameters, as well as locomotion, motor coordination, strength, anxiety, and depressive-like behaviors, were evaluated for 10 days. After that, the brain and blood were collected for further analysis of cytokines (interleukin 1? and interleukin 6), brain-derived neurotrophic factor (BDNF), and the immunocontents of total and phosphorylated Tropomyosin receptor kinase B (TrkB). The results demonstrated that the acute and prolonged treatment with HEEb was able to reduce both mechanical and thermal nociception. It was also possible to observe an increase in the strength, without changing locomotion and motor coordination parameters. Interestingly, treatment with HEEb reduces anxious and depressive-like behaviors. Finally, we observed a reduction in inflammatory cytokines in the hippocampus of animals treated with HEEb, while an increase in BDNF was observed in the prefrontal cortex (PFC). However, no alterations related to total and phosphorylated TrkB receptor expression were found. Our study demonstrated the antinociceptive and emotional effects of HEEb in mice, possibly acting on neuroinflammatory and neurotrophic mechanisms. These data provide initial evidence about the E. brasiliensis potential for treating chronic pain.
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Analgésicos , Anti-Inflamatórios , Fator Neurotrófico Derivado do Encéfalo , Modelos Animais de Doenças , Fibromialgia , Extratos Vegetais , Folhas de Planta , Reserpina , Animais , Analgésicos/farmacologia , Analgésicos/uso terapêutico , Camundongos , Extratos Vegetais/farmacologia , Extratos Vegetais/uso terapêutico , Folhas de Planta/química , Fibromialgia/tratamento farmacológico , Fibromialgia/induzido quimicamente , Fator Neurotrófico Derivado do Encéfalo/metabolismo , Anti-Inflamatórios/farmacologia , Anti-Inflamatórios/uso terapêutico , Masculino , Receptor trkB/metabolismo , Emoções/efeitos dos fármacos , Citocinas/metabolismo , Depressão/tratamento farmacológico , Depressão/induzido quimicamente , Ansiedade/tratamento farmacológico , Ansiedade/induzido quimicamente , Comportamento Animal/efeitos dos fármacosRESUMO
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.
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Fator Neurotrófico Derivado do Encéfalo , Modelos Animais de Doenças , Terapia com Luz de Baixa Intensidade , Fator de Crescimento Neural , Regeneração Nervosa , Complexo Vitamínico B , Animais , Ratos , Regeneração Nervosa/efeitos da radiação , Terapia com Luz de Baixa Intensidade/métodos , Fator Neurotrófico Derivado do Encéfalo/metabolismo , Fator de Crescimento Neural/metabolismo , Masculino , Laminina/metabolismo , Traumatismos do Nervo Facial/radioterapia , Traumatismos do Nervo Facial/terapia , Ratos Wistar , Proteína Básica da Mielina/metabolismoRESUMO
Brain-derived neurotrophic factor (BDNF) and its tropomyosin receptor kinase B (TrkB) are important signaling proteins that regulate dendritic growth and maintenance in the central nervous system (CNS). After binding of BDNF, TrkB is endocytosed into endosomes and continues signaling within the cell soma, dendrites, and axon. In previous studies, we showed that BDNF signaling initiated in axons triggers long-distance signaling, inducing dendritic arborization in a CREB-dependent manner in cell bodies, processes that depend on axonal dynein and TrkB activities. The binding of BDNF to TrkB triggers the activation of different signaling pathways, including the ERK, PLC-γ and PI3K-mTOR pathways, to induce dendritic growth and synaptic plasticity. How TrkB downstream pathways regulate long-distance signaling is unclear. Here, we studied the role of PLC-γ-Ca2+ in BDNF-induced long-distance signaling using compartmentalized microfluidic cultures. We found that dendritic branching and CREB phosphorylation induced by axonal BDNF stimulation require the activation of PLC-γ in the axons of cortical neurons. Locally, in axons, BDNF increases PLC-γ phosphorylation and induces intracellular Ca2+ waves in a PLC-γ-dependent manner. In parallel, we observed that BDNF-containing signaling endosomes transport to the cell body was dependent on PLC-γ activity and intracellular Ca2+ stores. Furthermore, the activity of PLC-γ is required for BDNF-dependent TrkB endocytosis, suggesting a role for the TrkB/PLC-γ signaling pathway in axonal signaling endosome formation.
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Abnormal cognitive and sensorial properties have been reported in patients with psychiatric and neurodevelopmental conditions, such as attention deficit hyperactivity disorder (ADHD). ADHD patients exhibit impaired dopaminergic signaling and plasticity in brain areas related to cognitive and sensory processing. The spontaneous hypertensive rat (SHR), in comparison to the Wistar Kyoto rat (WKY), is the most used genetic animal model to study ADHD. Brain neurotrophic factor (BDNF), critical for midbrain and hippocampal dopaminergic neuron survival and differentiation, is reduced in both ADHD subjects and SHR. Physical exercise (e.g. swimming) promotes neuroplasticity and improves cognition by increasing BDNF and irisin. Here we investigate the effects of gestational swimming on sensorial and behavioral phenotypes, striatal dopaminergic parameters, and hippocampal FNDC5/irisin and BDNF levels observed in WKY and SHR. Gestational swimming improved nociception in SHR rats (p = 0.006) and increased hippocampal BDNF levels (p = 0.02) in a sex-dependent manner in adolescent offspring. Sex differences were observed in hippocampal FNDC5/irisin levels (p = 0.002), with females presenting lower levels than males. Our results contribute to the notion that swimming during pregnancy is a promising alternative to improve ADHD phenotypes in the offspring.
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Transtorno do Deficit de Atenção com Hiperatividade , Humanos , Ratos , Feminino , Masculino , Animais , Adolescente , Fator Neurotrófico Derivado do Encéfalo/metabolismo , Fibronectinas , Nociceptividade , Encéfalo/metabolismo , Ratos Endogâmicos SHR , Ratos Endogâmicos WKY , Modelos Animais de DoençasRESUMO
The present study aimed to evaluate if sepsis sensitizes behavioural and biochemical responses induced by m-amphetamine. For this, Wistar rats were submitted to the cecal ligation and puncture. After 30 days of cecal ligation and puncture procedure, the animals were submitted to a single intraperitoneal injection of saline or m-amphetamine (.25, .50, or 1.0 mg/kg). Locomotor behaviour was assessed 2 h after the administration. Interleukin (IL)-1ß, IL-6, IL-10, tumour necrosis factor-α, dopamine-cAMP-regulated phosphoprotein of 32,000 kDa (DARPP-32) and neuronal calcium sensor (NCS-1) levels were evaluated in the frontal cortex, hippocampus and striatum. Also, brain-derived neurotrophic factor (BDNF), neuronal growth factor and glial-derived neurotrophic factor levels were assessed in the hippocampus. M-amphetamine alone (.25 and 1.0 mg/kg) increased rats' locomotion and exploratory behaviour compared with the Sham + Sal. Animals from the cecal ligation and puncture + m-amphetamine (.5 and/or 1.0 mg/kg) group showed an increase in locomotion, exploratory and risk-like behaviour when compared with the Sham + Saline group and with its respective Sham groups. Cecal ligation and puncture increased interleukin levels compared with the Sham + Sal. However, cecal ligation and puncture animals that received m-amphetamine (1 mg/kg) increased even more, these inflammatory parameters compared with the Sham + Sal and the cecal ligation and puncture + saline group. M-amphetamine at lower doses increased neurotrophic factors, but higher doses decreased these parameters in the brain of cecal ligation and puncture rats. M-amphetamine dose-dependently increased DARPP-32 and NCS-1 levels in cecal ligation and puncture rats in some structures. In conclusion, these results demonstrate that sepsis sensitizes behavioural amphetamine responses while inducing inflammatory and neurotrophic vulnerability in the cecal ligation and puncture model.
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Anfetamina , Sepse , Ratos , Animais , Ratos Wistar , Anfetamina/farmacologia , Punções , Modelos Animais de DoençasRESUMO
BACKGROUND: Acute pancreatitis is an inflammation of the pancreatic glandular parenchyma that causes injury with or without the destruction of pancreatic acini. Clinical and experimental evidence suggest that certain systemic proinflammatory mediators may be responsible for initiating the fundamental mechanisms involved in microglial reactivity. Here, we investigated the possible repercussions of acute pancreatitis (AP) on the production of inflammatory mediators in the brain parenchyma focusing on microglial activation in the hippocampus. METHODS: The acute pancreatic injury in rats was induced by a pancreas ligation surgical procedure (PLSP) on the splenic lobe, which corresponds to approximately 10% of total mass of the pancreas. Blood samples were collected via intracardiac puncture for the measurement of serum amylase. After euthanasia, frozen or paraffin-embedded brains and pancreas were analyzed using qRT-PCR or immunohistochemistry, respectively. RESULTS: Immunohistochemistry assays showed a large number of Iba1 and PU.1-positive cells in the CA1, CA3, and dentate gyrus (DG) regions of the hippocampus of the PLSP group. TNF-α mRNA expression was significantly higher in the brain from PLSP group. NLRP3 inflammasome expression was found to be significantly increased in the pancreas and brain of rats of the PLSP group. High levels of BNDF mRNA were found in the rat brain of PLSP group. In contrast, NGF mRNA levels were significantly higher in the control group versus PLSP group. CONCLUSION: Our findings suggest that AP has the potential to induce morphological changes in microglia consistent with an activated phenotype.
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Pancreatite , Ratos , Animais , Pancreatite/metabolismo , Microglia/metabolismo , Doença Aguda , Hipocampo/metabolismo , Pâncreas/metabolismo , RNA Mensageiro/metabolismoRESUMO
SUMMARY 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.
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The aging population poses a serious challenge concerning an increased prevalence of Alzheimer's disease (AD) and its impact on global burden, morbidity, and mortality. Oxidative stress, as a molecular hallmark that causes susceptibility in AD, interplays to other AD-related neuropathology cascades and decreases the expression of central and circulation brain-derived neurotrophic factor (BDNF), an essential neurotrophin that serves as nerve development and survival, and synaptic plasticity in AD. By its significant correlation with the molecular and clinical progression of AD, BDNF can potentially be used as an objectively accurate biomarker for AD diagnosis and progressivity follow-up in future clinical practice. This comprehensive review highlights the oxidative stress interplay with BDNF in AD neuropathology and its potential use as an AD biomarker.
O envelhecimento da população representa um sério desafio no que diz respeito ao aumento da prevalência da doença de Alzheimer (DA) e o seu impacto na carga, morbidade e mortalidade globais. O estresse oxidativo, como uma marca molecular que causa suscetibilidade na DA, interage com outras cascatas de neuropatologia relacionadas à DA e diminui a expressão do fator neurotrófico encefálico (brain-derived neurotrophic factor BDNF), uma neurotrofina essencial que serve como desenvolvimento e sobrevivência nervosa, e plasticidade sináptica na DA. Pela sua correlação significativa com a progressão molecular e clínica da DA, o BDNF pode potencialmente ser usado como um biomarcador objetivamente preciso para o diagnóstico da DA e acompanhamento da progressividade na prática clínica futura. Esta revisão abrangente destacou a interação do estresse oxidativo com o BDNF na neuropatologia da DA e seu uso potencial como biomarcador da DA.
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Cuando se produce una erosión corneal y fracasa la epitelización corneal surgen los defectos epiteliales corneales persistentes, cuyo tratamiento es un desafío para el oftalmólogo. Es muy frecuente el fracaso del tratamiento convencional por lo que se mantiene el interés en la búsqueda de otros factores de crecimiento para la cicatrización epitelial tales como los colirios de insulina. La insulina es un péptido estrechamente relacionado con el factor de crecimiento similar a la insulina 1. Su mecanismo de acción no es bien comprendido, sin embargo se acepta que es capaz de inducir migración y proliferación de las células epiteliales corneales, por lo que promueve y acelera la reepitelización de defectos epiteliales persistentes refractarios a tratamiento. La ausencia de una presentación comercial de colirio de insulina, hace necesario conocer su estabilidad físicoquímica y microbiológica así como la eficacia, efectividad y seguridad del colirio de insulina a diferentes concentraciones. De ahí la motivación para realizar una revisión de la literatura existente sobre el empleo del colirio de insulina en el tratamiento del defecto epitelial corneal persistente. Se realizó la búsqueda en bases de datos electrónicas como PubMed Central, EBSCO, Clinical Trials.gov, MEDLINE OVID, EMBASE OVID con el objeto de identificar artículos relacionados con el tema(AU)
When corneal erosion occurs and corneal epithelialization fails, persistent corneal epithelial defects arise, whose treatment is a challenge for the ophthalmologist. The failure of conventional treatment is very frequent; therefore, there is still interest in the search for other growth factors for epithelial healing, such as insulin eye drops. Insulin is a peptide closely related to insulin-like growth factor 1. Its mechanism of action is not well understood; however, it is accepted that it is capable of inducing migration and proliferation of corneal epithelial cells, thereby promoting and accelerating reepithelialization of persistent epithelial defects refractory to treatment. The absence of a commercial presentation for insulin eye drops makes it necessary to know its physicochemical and microbiological stability, as well as the efficacy, effectiveness and safety of insulin eye drops at different concentrations; hence the motivation to review the existing literature on the use of insulin eye drops in the treatment of persistent corneal epithelial defects. The search was carried out in electronic databases such as PubMed Central, EBSCO, Clinical Trials.gov, MEDLINE OVID, EMBASE OVID, with the aim of identifying relevant articles related to the topic(AU)
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Humanos , Células Epiteliais , Literatura de Revisão como Assunto , Bases de Dados BibliográficasRESUMO
BACKGROUND: The prairie vole (Microtus ochrogaster) is a socially monogamous rodent that establishes an enduring pair bond after cohabitation, with (6 h) or without (24 h) mating. Previously, we reported that social interaction and mating increased cell proliferation and differentiation to neuronal fate in neurogenic niches in male voles. We hypothesized that neurogenesis may be a neural plasticity mechanism involved in mating-induced pair bond formation. Here, we evaluated the differentiation potential of neural progenitor cells (NPCs) isolated from the subventricular zone (SVZ) of both female and male adult voles as a function of sociosexual experience. Animals were assigned to one of the following groups: (1) control (Co), sexually naive female and male voles that had no contact with another vole of the opposite sex; (2) social exposure (SE), males and females exposed to olfactory, auditory, and visual stimuli from a vole of the opposite sex, but without physical contact; and (3) social cohabitation with mating (SCM), male and female voles copulating to induce pair bonding formation. Subsequently, the NPCs were isolated from the SVZ, maintained, and supplemented with growth factors to form neurospheres in vitro. RESULTS: Notably, we detected in SE and SCM voles, a higher proliferation of neurosphere-derived Nestin + cells, as well as an increase in mature neurons (MAP2 +) and a decrease in glial (GFAP +) differentiated cells with some sex differences. These data suggest that when voles are exposed to sociosexual experiences that induce pair bonding, undifferentiated cells of the SVZ acquire a commitment to a neuronal lineage, and the determined potential of the neurosphere is conserved despite adaptations under in vitro conditions. Finally, we repeated the culture to obtain neurospheres under treatments with different hormones and factors (brain-derived neurotrophic factor, estradiol, prolactin, oxytocin, and progesterone); the ability of SVZ-isolated cells to generate neurospheres and differentiate in vitro into neurons or glial lineages in response to hormones or factors is also dependent on sex and sociosexual context. CONCLUSION: Social interactions that promote pair bonding in voles change the properties of cells isolated from the SVZ. Thus, SE or SCM induces a bias in the differentiation potential in both sexes, while SE is sufficient to promote proliferation in SVZ-isolated cells from male brains. In females, proliferation increases when mating is performed. The next question is whether the rise in proliferation and neurogenesis of cells from the SVZ are plastic processes essential for establishing, enhancing, maintaining, or accelerating pair bond formation. Highlights 1. Sociosexual experiences that promote pair bonding (social exposure and social cohabitation with mating) induce changes in the properties of neural stem/progenitor cells isolated from the SVZ in adult prairie voles. 2. Social interactions lead to increased proliferation and induce a bias in the differentiation potential of SVZ-isolated cells in both male and female voles. 3. The differentiation potential of SVZ-isolated cells is conserved under in vitro conditions, suggesting a commitment to a neuronal lineage under a sociosexual context. 4. Hormonal and growth factors treatments (brain-derived neurotrophic factor, estradiol, prolactin, oxytocin, and progesterone) affect the generation and differentiation of neurospheres, with dependencies on sex and sociosexual context. 5. Proliferation and neurogenesis in the SVZ may play a crucial role in establishing, enhancing, maintaining, or accelerating pair bond formation.
In this study, researchers evaluated whether social interactions and copulation induce changes in the proliferation and differentiation of neural progenitor cells in adult male and female voles using an in vitro neurosphere formation assay. The following groups were assigned: control animals without any exposure to another vole outside their litter, another group with social exposure consisting of sensory exposure to a vole of the opposite sex and a third group with social cohabitation and copulation. Forty eight hours after social interactions, cells were isolated from the neurogenic niche subventricular zone (SVZ) and cultured to assess their self-renewal and proliferation abilities to form neurospheres. The results showed in the social interaction groups, a greater number and growth of neurospheres in both males and females. Differentiation capacity was assessed by immunodetection of MAP2 and GFAP to identify neurons or glia, respectively, arise from neurospheres, with an increase in neuronal fate in groups with social interaction. In the second part of the study, the researchers analyzed the effect of different hormone and growth factor treatments and found that the response in both proliferation and differentiation potential may vary depending on the sociosexual context or sex. This study suggests that social interactions leading to pair bond formation alter the properties of SVZ cells, whereby proliferation and neurogenesis may have an impact on the establishment and maintenance of pair bonding.
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Células-Tronco Neurais , Caracteres Sexuais , Animais , Feminino , Masculino , Fator Neurotrófico Derivado do Encéfalo/metabolismo , Ocitocina/metabolismo , Pradaria , Prolactina/metabolismo , Progesterona , Neurônios/metabolismo , Encéfalo/metabolismo , Células-Tronco Neurais/metabolismo , Arvicolinae/metabolismo , Proliferação de Células , Estradiol/metabolismo , Proteínas de Ligação a DNA/metabolismoRESUMO
Glia comprise a heterogeneous group of cells involved in the structure and function of the central and peripheral nervous system. Glial cells are found from invertebrates to humans with morphological specializations related to the neural circuits in which they are embedded. Glial cells modulate neuronal functions, brain wiring and myelination, and information processing. For example, astrocytes send processes to the synaptic cleft, actively participate in the metabolism of neurotransmitters, and release gliotransmitters, whose multiple effects depend on the targeting cells. Human astrocytes are larger and more complex than their mice and rats counterparts. Astrocytes and microglia participate in the development and plasticity of neural circuits by modulating dendritic spines. Spines enhance neuronal connectivity, integrate most postsynaptic excitatory potentials, and balance the strength of each input. Not all central synapses are engulfed by astrocytic processes. When that relationship occurs, a different pattern for thin and large spines reflects an activity-dependent remodeling of motile astrocytic processes around presynaptic and postsynaptic elements. Microglia are equally relevant for synaptic processing, and both glial cells modulate the switch of neuroendocrine secretion and behavioral display needed for reproduction. In this chapter, we provide an overview of the structure, function, and plasticity of glial cells and relate them to synaptic maturation and modulation, also involving neurotrophic factors. Together, neurons and glia coordinate synaptic transmission in both normal and abnormal conditions. Neglected over decades, this exciting research field can unravel the complexity of species-specific neural cytoarchitecture as well as the dynamic region-specific functional interactions between diverse neurons and glial subtypes.
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Espinhas Dendríticas , Neuroglia , Animais , Humanos , Camundongos , Ratos , Astrócitos , Microglia , NeurôniosRESUMO
To study the process of neuronal differentiation, the human neuroblastoma (SH-SY5Y) and the murine neuroblastoma (Neuro2a) cell lines have proven to be effective models. For this approach, different protocols involving known neurotrophic factors and other molecules, such as retinoic acid (RA), have been assessed to better understand the neuronal differentiation process. Thus, the goal of this manuscript was to provide a brief overview of recent studies that have used protocols to promote neurodifferentiation in SH-SY5Y and Neuro2a cell lines and used acquired morphology and neuronal markers to validate whether differentiation was effective. The published results supply some guidance regarding the relationship between RA and neurotrophins for SH-SY5Y, as well a serum concentrations for both cell lines. Furthermore, they demonstrate the potential application of Neuro2a, which is critical for future research on neuronal differentiation.
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Células-Tronco Neurais , Neuroblastoma , Humanos , Camundongos , Animais , Linhagem Celular Tumoral , Neuroblastoma/metabolismo , Tretinoína/farmacologia , Células-Tronco Neurais/metabolismo , Diferenciação CelularRESUMO
BACKGROUND: Transcranial direct current stimulation (tDCS) and foot drop stimulators (FDS) are widely used for stroke rehabilitation. However, no study has investigated if tDCS could boost the effects of FDS and gait training in improving clinical parameters and neuroplasticity biomarkers of chronic post-stroke subjects. OBJECTIVE: To investigate the effects of combining tDCS and FDS on motor impairment, functional mobility, and brain-derived neurotrophic factor (BDNF) serum levels. Also, to evaluate the effects of this protocol on the insulin-like growth factor-1 (IGF-1), insulin growth factor-binding proteins-3 (IGFBP-3), interleukin (IL) 6 and 10, and tumor necrosis factor-α (TNF-α) levels. METHODS: Thirty-two chronic post-stroke individuals were randomized to tDCS plus FDS or sham tDCS plus FDS groups. Both groups underwent ten gait training sessions for two weeks using a FDS device and real or sham tDCS. Blood samples and clinical data were acquired before and after the intervention. Motor impairment was assessed by the Fugl-Meyer Assessment and functional mobility using the Timed up and Go test. RESULTS: Both groups improved the motor impairment and functional mobility and increased the BDNF levels. Both groups also increased the IL-10 and decreased the cortisol, IL-6, and TNF-α levels. No difference was observed between groups. CONCLUSION: tDCS did not add effect to FDS and gait training in improving clinical parameters and neuroplasticity biomarkers in chronic post-stroke individuals. Only FDS and gait training might be enough for people with chronic stroke to modify some clinical parameters and neuroplasticity biomarkers.
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In this retrospective study, we aimed to evaluate the effects of the neurotrophic compound Cerebrolysin on executive, cognitive, and functional performance in patients with traumatic brain injury (TBI) with a highly severe disability level. A total of 44 patients were included in the study, with 33 patients in the control group and 11 patients in the interventional group who received intravenous infusions of 30 mL Cerebrolysin. Both groups received standard rehabilitation therapy following the rehabilitation protocol for patients with TBI at Hospital Clínico Mutual de Seguridad. Functional and cognitive scales were evaluated at baseline, at four months, and at the endpoint of the intervention therapy at seven months (on average). The results revealed a significant improvement in the Cerebrolysin-treated group compared to the control group. Specifically, patients who received Cerebrolysin showed a moderate residual disability and a significant reduction in the need for care. Concerning the promising results and considering the limitations of the retrospective study design, we suggest that randomized controlled studies be initiated to corroborate the positive findings for Cerebrolysin in patients with moderate to severe brain trauma.
Assuntos
Lesões Encefálicas Traumáticas , Lesões Encefálicas , Humanos , Estudos Retrospectivos , Lesões Encefálicas/reabilitação , Lesões Encefálicas Traumáticas/tratamento farmacológico , Cognição , Recuperação de Função FisiológicaRESUMO
Treatment-resistant depression (TRD), characterized by the failure to achieve symptomatic remission despite multiple pharmacotherapeutic treatments, poses a significant challenge for clinicians. Electroconvulsive therapy (ECT) is an effective but limited option due to its cognitive side effects. In this context, magnetic seizure therapy (MST) has emerged as a promising alternative, offering comparable antidepressant efficacy with better cognitive outcomes. However, the clinical outcomes and cognitive effects of MST require further investigation. This double-blinded, randomized, non-inferiority study aims to compare the efficacy, tolerability, cognitive adverse effects, and neurophysiological biomarkers of MST with bilateral ECT (BT ECT) in patients with TRD. This study will employ multimodal nuclear magnetic resonance imaging (MRI) and serum neurotrophic markers to gain insight into the neurobiological basis of seizure therapy. Additionally, neurophysiological biomarkers will be evaluated as secondary outcomes to predict the antidepressant and cognitive effects of both techniques. The study design, recruitment methods, ethical considerations, eligibility criteria, interventions, and blinding procedures are described. The expected outcomes will advance the field by offering a potential alternative to ECT with improved cognitive outcomes and a better understanding of the underlying pathophysiology of depression and antidepressant therapies.
RESUMO
This study aimed to evaluate Haloperidol's (Hal) effects on the behavioral, neurotrophic factors, and epigenetic parameters in an animal model of schizophrenia (SCZ) induced by ketamine (Ket). Injections of Ket or saline were administered intraperitoneal (once a day) between the 1st and 14th days of the experiment. Water or Hal was administered via gavage between the 8th and 14th experimental days. Thirty minutes after the last injection, the animals were subjected to behavioral analysis. The activity of DNA methyltransferase (DNMT), histone deacetylase (HDAC), and histone acetyltransferase and levels of brain-derived neurotrophic factor (BDNF), nerve growth factor (NGF), neurotrophin-3 (NT-3), and glial-derived neurotrophic factor (GDNF) were evaluated in the frontal cortex, hippocampus, and striatum. Ket increased the covered distance and time spent in the central area of the open field, and Hal did not reverse these behavioral alterations. Significant increases in the DNMT and HDAC activities were detected in the frontal cortex and striatum from rats that received Ket, Hal, or a combination thereof. Besides, Hal per se increased the activity of DNMT and HDAC in the hippocampus of rats. Hal per se or the association of Ket plus Hal decreased BDNF, NGF, NT-3, and GDNF, depending on the brain region and treatment regimen. The administration of Hal can alter the levels of neurotrophic factors and the activity of epigenetic enzymes, which can be a factor in the development of effect collateral in SCZ patients. However, the precise mechanisms involved in these alterations are still unclear.