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The study of social interactions lies at the core of several disciplines such as psychiatry, psychology and ethology, just to name a few. In this context, understanding the temporal patterns underlying interactive behaviors is of crucial importance. Here, we employed T-pattern detection and analysis to study social interactions in ten pairs of Wistar rats tested in an Open-Field environment. We found four different categories of interactive behaviors. One of them was of particular interest to us because it consisted of behavioral events that, taken individually, should not underlie an interaction of any kind; however, they were included in T-patterns, which is suggestive of a dyadic temporal coordination in the behavioral expression of two individuals. Within this category, we described for the first time a new subcategory of apparent interaction patterns characterized by events that one of the two rats repeats only if previously produced by the partner (i.e., behavioral mirroring). These findings are discussed in functional terms for rodents and in light of our current understanding of social interactions in humans.
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Conducta Animal , Ratas Wistar , Animales , Conducta Animal/fisiología , Ratas , Masculino , Interacción Social , Conducta SocialRESUMEN
Background: A rodent autism spectrum disorder (ASD) model based on prenatal exposure to valproic acid (VPA) is widely recognized as a prominent model. Social behavior in rodent ASD models has primarily been evaluated through a three-chamber approach test. However, in this study, we focused on social attention in the VPA model of ASD. Methods: In male C57BL/6 J mice, attentional behaviors toward conspecifics were examined through reaching tasks around 9-11 weeks of age. On embryonic day 12.5, pregnant mice underwent a subcutaneous injection of 600 mg/kg VPA sodium salt dissolved in 0.9% saline solution (VPA group) or saline solution alone (Sal group) into their neck fat. Thirty-six mice-nine each in the VPA and saline groups, and 18 partners-underwent training in reaching behavior. Subsequently, we examined whether the VPA or Sal group demonstrated focused attention toward their partners during reaching tasks. A two-way analysis of variance (ANOVA) (condition [VPA/Sal] × situation [face-to-face (attention)/not paying attention (not attention)]) was conducted on the average success rate of the situation. Additionally, we measured the duration of sniffing behavior between pairs of mice in an open field twice in total at 4 and 8 weeks of age before reaching task. The pairs were constructed by pairing a VPA or Sal group mouse with its partner, with the objective of facilitating initial encounters between the mice. A one-way ANOVA was conducted on the average duration of sniffing behavior data from 4 weeks and a second one-way ANOVA on data from 8 weeks. Results: The analysis revealed a significant interaction between condition and situation in the reaching task [F (1, 28) = 6.75, p = 0.015, ηp 2 = 0.19]. The simple main effect test exhibited that the "not paying attention" rate was significantly higher than that of the "face-to-face" in the VPA group (p < 0.01). The results revealed a not significant difference in the average duration of sniffing behavior at 4 weeks [F (3, 32) = 2.71, p = 0.06, n.s., ηp 2 = 0.20], but significant difference at 8 weeks [F (3, 32) = 4.12, p < 0.05, ηp 2 = 0.28]. Multiple comparisons using the Bonferroni method revealed significant differences in the sniffing duration at 8 weeks between from the partner toward the VPA mouse and from the partner toward the Sal mouse (p < 0.05). Conclusion: The VPA rodent model of ASD exhibited differences in social attention compared to the saline group. By focusing on social attention and exploring various ASD models, insights can be gained from the neural mechanisms underlying gaze abnormalities during social interaction in individuals with ASD.
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Nitrate leaching, greenhouse gas emissions, and water loss are caused by conventional water and fertilizer management in vegetable fields. The Expert-N system is a useful tool for recommending the optimal nitrogen (N) fertilizer for vegetable cultivation. To clarify the fates of water and N in vegetable fields, an open-field vegetable cultivation experiment was conducted in Dongbeiwang, Beijing. This experiment tested two irrigation treatments (W1: conventional and W2: optimal) and three fertilizer treatments (N1: conventional, N2: optimal N rate by Expert-N system, and N3: 80% optimal N rate) on cauliflower (Brassica oleracea L.), amaranth (Amaranthus tricolor L.), and spinach (Spinacia oleracea L.). The EU-Rotate_N model was used to simulate the fates of water and N in the soil. The results indicated that the yields of amaranth and spinach showed no significant differences among all the treatments in 2000 and 2001. However, cauliflower yield under the W1N2 and W1N3 treatments obviously reduced in 2001. Compared with the W1 treatment, W2 reduced irrigation amount by 27.9-29.8%, water drainage by over 76%, increased water use efficiency by 5-17%, and irrigation water use efficiency by 29-45%. Nitrate leaching was one of the main pathways in this study, accounting for 8.4% of the total N input; compared to N1, the input of fertilizer N under the N2 and N3 treatments decreased by over 66.5%, consequently reducing gaseous N by 48-72% and increasing nitrogen use efficiency (NUE) by 17-37%. Additionally, compared with the W1 treatments, gaseous N loss under the W2 treatments was reduced by 18-26% and annual average NUEs increased by 22-29%. The highest annual average NUEs were under W2N3 (169.6 kg kg-1) in 2000 and W2N2 (188.0 kg kg-1) in 2001, respectively. We found that optimizing fertilizer management allowed subsequent crops to utilize residual N in the soil. Therefore, we suggest that the W2N3 management should be recommended to farmers to reduce water and N loss in vegetable production systems.
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One aspect of reproducibility in preclinical research that is frequently overlooked is the physical condition in which physiological, pharmacological, or behavioural recordings are conducted. In this study, the physical conditions of mice were altered through the attachments of wireless electrophysiological recording devices (Neural Activity Tracker-1, NAT-1). NAT-1 devices are miniaturised multichannel devices with onboard memory for direct high-resolution recording of brain activity for >48 h. Such devices may limit the mobility of animals and affect their behavioural performance due to the added weight (total weight of approximately 3.4 g). The mice were additionally treated with saline (control), N-methyl-D-aspartate (NMDA) receptor antagonist MK801 (0.85 mg/kg), or the muscarinic acetylcholine receptor blocker scopolamine (0.65 mg/kg) to allow exploration of the effect of NAT-1 attachments in pharmacologically treated mice. We found only minimal differences in behavioural outcomes with NAT-1 attachments in standard parameters of locomotor activity widely reported for the open field test between the drug treatments. Hypoactivity was globally observed as a consistent outcome in the MK801-treated mice and hyperactivity in scopolamine groups regardless of NAT-1 attachments. These data collectively confirm the reproducibility for combined behavioural, pharmacological, and physiological endpoints even in the presence of lightweight wireless data loggers. The NAT-1 therefore constitutes a pertinent tool for investigating brain activity in, e.g., drug discovery and models of neuropsychiatric and/or neurodegenerative diseases with minimal effects on pharmacological and behavioural outcomes.
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Maleato de Dizocilpina , Electroencefalografía , Conducta Exploratoria , Escopolamina , Animales , Escopolamina/farmacología , Maleato de Dizocilpina/farmacología , Ratones , Masculino , Conducta Exploratoria/efectos de los fármacos , Conducta Animal/efectos de los fármacos , Prueba de Campo Abierto/efectos de los fármacosRESUMEN
Traumatic brain injury (TBI) survivors face debilitating long-term psychosocial consequences, including social isolation and depression. TBI modifies neurovascular physiology and behavior but the chronic physiological implications of altered brain perfusion on social interactions are unknown. Adult C57/BL6 male mice received a moderate cortical TBI, and social behaviors were assessed at baseline, 3-, 7-, 14-, 30-, and 60-days post injury (dpi). Magnetic resonance imaging (MRI, 9.4T) using dynamic susceptibility contrast perfusion weighted MRI were acquired. At 60dpi mice underwent histological angioarchitectural mapping. Analysis utilized standardized protocols followed by cross-correlation metrics. Social behavior deficits at 60dpi emerged as reduced interactions with a familiar cage-mate (partner) that mirrored significant reductions in cerebral blood flow (CBF) at 60dpi. CBF perturbations were dynamic temporally and across brain regions including regions known to regulate social behavior such as hippocampus, hypothalamus, and rhinal cortex. Social isolation in TBI-mice emerged with a significant decline in preference to spend time with a cage mate. Cortical vascular density was also reduced corroborating the decline in brain perfusion and social interactions. Thus, the late emergence of social interaction deficits mirrored the reduced vascular density and CBF in regions known to be involved in social behaviors. Vascular morphology and function improved prior to the late decrements in social function and our correlations strongly implicate a linkage between vascular density, cerebral perfusion, and social interactions. Our study provides a clinically relevant timeline of alterations in social deficits alongside functional vascular recovery that can guide future therapeutics.
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Lesiones Traumáticas del Encéfalo , Circulación Cerebrovascular , Imagen por Resonancia Magnética , Ratones Endogámicos C57BL , Animales , Masculino , Lesiones Traumáticas del Encéfalo/complicaciones , Lesiones Traumáticas del Encéfalo/fisiopatología , Lesiones Traumáticas del Encéfalo/patología , Lesiones Traumáticas del Encéfalo/diagnóstico por imagen , Lesiones Traumáticas del Encéfalo/psicología , Ratones , Circulación Cerebrovascular/fisiología , Conducta Social , Trastornos Cerebrovasculares/fisiopatología , Trastornos Cerebrovasculares/diagnóstico por imagen , Trastornos Cerebrovasculares/patología , Aislamiento Social/psicología , Encéfalo/patología , Encéfalo/fisiopatología , Encéfalo/diagnóstico por imagenRESUMEN
INTRODUCTION: The traditional medicinal system of India, Ayurveda, has mentioned Cordia Dichotoma as a potential treatment for various ailments. In the current research, the extracts of Cordia Dichotoma was examined to evaluate their antidepressant potential. MATERIALS AND METHODS: Here, green leaves of Cordia Dichotoma were used to prepare chloroform, ethanol, and aqueous extracts (referred to as CdCe, CdEe, and CdAe respectively). The research focused on investigating the antidepressant effects of these extracts using behavioral models in experimental animals. Additionally, locomotor activity was assessed as part of the evaluation process. RESULTS: Immobility time was reduced with CdEe Cordia Dichotoma rFST & mTST when at 200 mg/kg and 400 mg/kg body weight. The CdAe showed reduction in immobility time in the repeated rFST) at 400 mg/kg, while in the mTST, significant effects were observed at 200 and 400 mg/kg. Regarding the chloroform extract, it only exhibited a significant reduction in immobility time in the modified Tail Suspension Test (mTST) at a low dose of 200 mg/kg. However, no noticeable change in motor dysfunction was observed with CCl4 and aqueous extracts at doses of 200 and 400 mg/kg. It is worth noting that the chloroform extract (CdCe) did lead to a significant decrease in locomotor activity at the same dosage level. Taken together, these findings suggest that extracts obtained from Cordia Dichotoma leaves may possess antidepressant properties.
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Antidepresivos , Cordia , Extractos Vegetales , Animales , Extractos Vegetales/farmacología , Antidepresivos/farmacología , Masculino , Ratones , Cordia/química , Hojas de la Planta/química , Fitoquímicos/farmacología , Conducta Animal/efectos de los fármacosRESUMEN
The etiology of interstitial cystitis/bladder pain syndrome (IC/BPS) is unknown but likely multifactorial. IC/BPS symptoms can be exacerbated by psychological stress, but underlying mechanisms remain to be defined. Transient receptor potential vanilloid 1 (TRPV1) channels, expressed on nerve fibers, have been implicated in bladder dysfunction and colonic hypersensitivity with stress in rodents. Histamine/H1R activation of TRPV1+ nerves increases bladder afferent fiber sensitivity to distension. TRPV1 channels are also expressed on mast cells, previously implicated in contributing to IC/BPS etiology and symptoms. We have examined the contribution of TRPV1 and mast cells to bladder dysfunction after repeated variate stress (RVS). RVS increased (P ≤ 0.05) serum and fecal corticosterone expression and induced anxiety-like behavior in wild-type (WT) mice. Intravesical instillation of the selective TRPV1 antagonist capsazepine (CPZ) rescued RVS-induced bladder dysfunction in WT mice. Trpv1 knockout (KO) mice did not increase voiding frequency with RVS and did not exhibit increased serum corticosterone expression despite exhibiting anxiety-like behavior. Mast cell-deficient mice (B6.Cg-Kitw-sh) failed to demonstrate RVS-induced increased voiding frequency or serum corticosterone expression, whereas control (no stress) mast cell-deficient mice had similar functional bladder capacity to WT mice. TRPV1 protein expression was significantly increased in the rostral lumbar (L1-L2) spinal cord and dorsal root ganglia (DRG) in WT mice exposed to RVS, but no changes were observed in lumbosacral (L6-S1) spinal segments or DRG. These studies demonstrated TRPV1 and mast cell involvement in RVS-induced increased voiding frequency and suggest that TRPV1 and mast cells may be useful targets to mitigate stress-induced urinary bladder dysfunction.NEW & NOTEWORTHY Using pharmacological tools and transgenic mice in a repeated variate stress (RVS) model in female mice, we demonstrate that transient receptor potential vanilloid 1 (TRPV1) and mast cells contribute to the increased voiding frequency observed following RVS. TRPV1 and mast cells should continue to be considered as targets to improve bladder function in stress-induced bladder dysfunction.
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Corticosterona , Mastocitos , Ratones Endogámicos C57BL , Ratones Noqueados , Estrés Psicológico , Canales Catiónicos TRPV , Vejiga Urinaria , Animales , Canales Catiónicos TRPV/metabolismo , Canales Catiónicos TRPV/genética , Mastocitos/metabolismo , Femenino , Vejiga Urinaria/metabolismo , Vejiga Urinaria/inervación , Estrés Psicológico/complicaciones , Estrés Psicológico/metabolismo , Corticosterona/sangre , Modelos Animales de Enfermedad , Cistitis Intersticial/metabolismo , Cistitis Intersticial/fisiopatología , Cistitis Intersticial/patología , Cistitis Intersticial/genética , Ratones , Micción , Capsaicina/farmacología , Capsaicina/análogos & derivados , Conducta Animal , Ansiedad/metabolismoRESUMEN
Anxiety fluctuates across the human menstrual cycle, with symptoms worsening during phases of declining or low ovarian hormones. Similar findings have been observed across the rodent estrous cycle, however, the magnitude and robustness of these effects have not been meta-analytically quantified. We conducted a systematic review and meta-analysis of estrous cycle effects on anxiety-like behaviour (124 articles; k = 259 effect sizes). In both rats and mice, anxiety-like behaviour was higher during metestrus/diestrus (lower ovarian hormones) than proestrus (higher ovarian hormones) (g = 0.44 in rats, g = 0.43 in mice). There was large heterogeneity in the data, which was partially accounted for by strain, experimental task, and reproductive status. Nonetheless, the effect of estrous cycle on anxiety-like behaviour was highly robust, with the fail-safe N test revealing the effect would remain significant even if 21,388 additional studies yielded null results. These results suggest that estrous cycle should be accounted for in studies of anxiety in females. Doing so will facilitate knowledge about menstrual-cycle regulation of anxiety disorders in humans.
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Ansiedad , Ciclo Estral , Miedo , Animales , Femenino , Ciclo Estral/fisiología , Ansiedad/fisiopatología , Ratas , Miedo/fisiología , Ratones , Conducta Animal/fisiologíaRESUMEN
This paper reviews the utility of zebrafish (Danio rerio) as a model system for exploring neurobehavioral phenomena in preclinical research, focusing on physiological processes, disorders, and neurotoxicity biomarkers. A comprehensive review of the current literature was conducted to summarize the various behavioral characteristics of zebrafish. The study examined the etiological agents used to induce neurotoxicity and the biomarkers involved, including Aß42, tau, MMP-13, MAO, NF-Ðß, and GFAP. Additionally, the different zebrafish study models and their responses to neurobehavioral analysis were discussed. The review identified several key biomarkers of neurotoxicity in zebrafish, each impacting different aspects of neurogenesis, inflammation, and neurodegeneration. Aß42 was found to alter neuronal growth and stem cell function. Tau's interaction with tubulin affected microtubule stability and led to tauopathies under pathological conditions. MMP-13 was linked to oxidative assault and sensory neuron degeneration. MAO plays a role in neurotransmitter metabolism and neurotoxicity conversion. NF-Ðß was involved in pro-inflammatory pathways, and GFAP was indicative of neuroinflammation and astroglial activation. Zebrafish provide a valuable model for neurobehavioral research, adhering to the "3Rs" philosophy. Their neurotoxicity biomarkers offer insights into the mechanisms of neurogenesis, inflammation, and neurodegeneration. This model system aids in evaluating physiological and pathological conditions, enhancing our understanding of neurobehavioral phenomena and potential therapeutic interventions.
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Introduction: Alcohol use disorder (AUD) is commonly associated with anxiety disorders and enhanced stress-sensitivity; symptoms that can worsen during withdrawal to perpetuate continued alcohol use. Alcohol increases neuroimmune activity in the brain. Our recent evidence indicates that alcohol directly modulates neuroimmune function in the central amygdala (CeA), a key brain region regulating anxiety and alcohol intake, to alter neurotransmitter signaling. We hypothesized that cannabinoids, such as cannabidiol (CBD) and ∆9-tetrahydrocannabinol (THC), which are thought to reduce neuroinflammation and anxiety, may have potential utility to alleviate alcohol withdrawal-induced stress-sensitivity and anxiety-like behaviors via modulation of CeA neuroimmune function. Methods: We tested the effects of CBD and CBD:THC (3:1 ratio) on anxiety-like behaviors and neuroimmune function in the CeA of mice undergoing acute (4-h) and short-term (24-h) withdrawal from chronic intermittent alcohol vapor exposure (CIE). We further examined the impact of CBD and CBD:THC on alcohol withdrawal behaviors in the presence of an additional stressor. Results: We found that CBD and 3:1 CBD:THC increased anxiety-like behaviors at 4-h withdrawal. At 24-h withdrawal, CBD alone reduced anxiety-like behaviors while CBD:THC had mixed effects, showing increased center time indicating reduced anxiety-like behaviors, but increased immobility time that may indicate increased anxiety-like behaviors. These mixed effects may be due to altered metabolism of CBD and THC during alcohol withdrawal. Immunohistochemical analysis showed decreased S100ß and Iba1 cell counts in the CeA at 4-h withdrawal, but not at 24-h withdrawal, with CBD and CBD:THC reversing alcohol withdrawal effects.. Discussion: These results suggest that the use of cannabinoids during alcohol withdrawal may lead to exacerbated anxiety depending on timing of use, which may be related to neuroimmune cell function in the CeA.
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Parkinson's disease (PD) is a severe neurodegenerative disease that disturbs human health. In the laboratory researches about PD, the mice model induced by intraperitoneal injection of 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) was widely used. However, there has been controversy about the model effectiveness to simulate PD symptoms and pathology, and the time-varying development of behavioral and pathological characteristic after MPTP treatment remains unclear. In order to solve these problems, we designed a series of experiments to evaluate this PD model at different time points. We constructed the subacute PD mouse model by intraperitoneal injection of MPTP for 5 consecutive days. The rotarod test, open field test and the immunohistochemical staining of tyrosine hydroxylase were conducted at -5, 1, 5, 7, 14, 21 and 28 days after the last injection of MPTP. The results showed that 5 days after the last MPTP administration, typical motor disorders with significant balance function damage in rotarod test began to appear and remained stable throughout the entire experiment. Simultaneously, we also observed the loss of tyrosine hydroxylase (TH) positive cells in the substantia nigra compacta and reduction of TH content in the striatum but this pathological change in the substantia nigra compacta reversed 21 days after injection. Besides, the spontaneous movement of mice in open field test remained unchanged by MPTP. This research indicated the time-dependence of MPTP neurotoxicity that impair the motor function and histological features and confirmed the symptom occurrence time after MPTP injection, which provides a reference for the future research about MPTP-induced PD.
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Drug-resistant epilepsy patients may benefit from non-pharmacological therapies, such as the ketogenic diet (KD). However, its high fat content poses compliance challenges and metabolic risks. To mitigate this, we developed a novel KD composition with less fat and additional nutrients (citrate, nicotinamide riboside, and omega-3 fatty acids) for ketone-independent neuroprotection. The efficacy, metabolic and neuropathological effects of the novel KD and a classic KD were compared to a control diet in the rapid kindling model of temporal lobe epilepsy. Both KD groups entered ketosis before kindling onset, with higher ketone levels in the classic KD group. Remarkably, rats on the novel KD had slower progression of behavioral seizures as compared to rats on a control diet, while this was not the case for rats on a classic KD. Both KDs reduced electrographic after-discharge duration, preserved neurons in the dorsal hippocampus, and normalized activity in open field tests. The novel KD, despite lower fat and ketone levels, demonstrated effective reduction of behavioral seizure severity while the classic KD did not, suggesting alternative mode(s) of action are involved. Additionally, the novel KD significantly mitigated liver triglyceride and plasma fatty acid levels compared to the classic KD, indicating a reduced risk of long-term liver steatosis. Our findings highlight the potential of the novel KD to enhance therapeutic efficacy and compliance in epilepsy patients.
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Dieta Cetogénica , Hígado Graso , Excitación Neurológica , Ratas Sprague-Dawley , Convulsiones , Animales , Dieta Cetogénica/métodos , Ratas , Masculino , Convulsiones/prevención & control , Convulsiones/dietoterapia , Convulsiones/metabolismo , Hígado Graso/prevención & control , Hígado Graso/dietoterapia , Hígado Graso/metabolismo , Modelos Animales de Enfermedad , Epilepsia del Lóbulo Temporal/prevención & control , Epilepsia del Lóbulo Temporal/dietoterapia , Epilepsia del Lóbulo Temporal/metabolismoRESUMEN
Fetal programming by subnutrition affects offspring's behaviour, metabolism, and sensitivity to stressors in sheep. The objective was to determine the stress response of ewes born to mothers nutritionally restricted during gestation to social isolation followed by exposure to a novel object. Twenty-six-year-old Corriedale ewes born to mothers who grazed high or low pasture allowances (HPA and LPA groups) from 23 days before conception until 122 days of gestation were used. Ewes were individually isolated in a novel place for 10â¯min, and 5â¯min after its beginning, an orange ball was dropped into the test pen. The ewes' behaviours were recorded during the test. Blood proteins, glucose and cortisol concentrations, heart and respiratory rates and rectal and surface temperatures were determined. The number of times looking at the ball tended to be greater in HPA ewes than LPA (6.7 ± 1.0 vs 4.7 ± 0.8, P = 0.08). The LPA ewes had greater serum albumin concentration than HPA ewes (3.2 ± 0.1â¯g/dL vs 3.0 ± 0.1â¯g/dL, P = 0.02), regardless of the applied stressors. Overall, the nutritional treatments applied to ewes during their intrauterine development did not modify the stress responses to social isolation followed by exposure to a novel object.
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Desnutrición , Aislamiento Social , Estrés Psicológico , Animales , Aislamiento Social/psicología , Femenino , Ovinos/fisiología , Desnutrición/psicología , Desnutrición/fisiopatología , Embarazo , Conducta Animal/fisiología , Hidrocortisona/sangre , Efectos Tardíos de la Exposición PrenatalRESUMEN
BACKGROUND: Cerebral small vessel disease is a common cause of vascular cognitive impairment and dementia. There is an urgent need for preventative treatments for vascular cognitive impairment and dementia, and reducing vascular dysfunction may provide a therapeutic route. Here, we investigate whether the chronic administration of nimodipine, a central nervous system-selective dihydropyridine calcium channel blocking agent, protects vascular, metabolic, and cognitive function in an animal model of cerebral small vessel disease, the spontaneously hypertensive stroke-prone rat. METHODS: Male spontaneously hypertensive stroke-prone rats were randomly allocated to receive either a placebo (n=24) or nimodipine (n=24) diet between 3 and 6 months of age. Animals were examined daily for any neurological deficits, and vascular function was assessed in terms of neurovascular and neurometabolic coupling at 3 and 6 months of age, and cerebrovascular reactivity at 6 months of age. Cognitive function was evaluated using the novel object recognition test at 6 months of age. RESULTS: Six untreated control animals were terminated prematurely due to strokes, including one due to seizure, but no treated animals experienced strokes and so had a higher survival (P=0.0088). Vascular function was significantly impaired with disease progression, but nimodipine treatment partially preserved neurovascular coupling and neurometabolic coupling, indicated by larger (P<0.001) and more prompt responses (P<0.01), and less habituation upon repeated stimulation (P<0.01). Also, animals treated with nimodipine showed greater cerebrovascular reactivity, indicated by larger dilation of arterioles (P=0.015) and an increase in blood flow velocity (P=0.001). This protection of vascular and metabolic function achieved by nimodipine treatment was associated with better cognitive function (P<0.001) in the treated animals. CONCLUSIONS: Chronic treatment with nimodipine protects from strokes, and vascular and cognitive deficits in spontaneously hypertensive stroke-prone rat. Nimodipine may provide an effective preventive treatment for stroke and cognitive decline in cerebral small vessel disease.
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Bloqueadores de los Canales de Calcio , Enfermedades de los Pequeños Vasos Cerebrales , Cognición , Modelos Animales de Enfermedad , Nimodipina , Ratas Endogámicas SHR , Animales , Nimodipina/farmacología , Nimodipina/uso terapéutico , Masculino , Enfermedades de los Pequeños Vasos Cerebrales/tratamiento farmacológico , Ratas , Cognición/efectos de los fármacos , Bloqueadores de los Canales de Calcio/farmacología , Bloqueadores de los Canales de Calcio/uso terapéutico , Circulación Cerebrovascular/efectos de los fármacos , Trastornos del Conocimiento/etiología , Trastornos del Conocimiento/tratamiento farmacológico , Trastornos del Conocimiento/prevención & controlRESUMEN
Growing evidence suggests that activators of nuclear factor erythroid-derived 2-like 2 (Nrf2), such as sulforaphane, may represent promising novel pharmacological targets for conditions related to oxidative stress, including depressive disorder. Therefore, we conducted a study to explore the behavioral and biochemical effects of repeated (14 days) sulforaphane (SFN) treatment in the olfactory bulbectomy (OB) animal model of depression. An open field test (OFT), splash test (ST), and spontaneous locomotor activity test (LA) were used to assess changes in depressive-like behavior and the potential antidepressant-like activity of SFN. The OB model induced hyperactivity in mice during the OFT and LA as well as a temporary loss of self-care and motivation in the ST. The repeated administration of SFN (10 mg/kg) effectively reversed these behavioral changes in OB mice across all tests. Additionally, a biochemical analysis revealed that SFN (10 mg/kg) increased the total antioxidant capacity in the frontal cortex and serum of the OB model. Furthermore, SFN (10 mg/kg) significantly enhanced superoxide dismutase activity in the serum of OB mice. Overall, the present study is the first to demonstrate the antidepressant-like effects of repeated SFN (10 mg/kg) treatment in the OB model and indicates that these benefits may be linked to improved oxidative status.
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To conserve sequential behavior in relation to the topographic challenges of space, it is proposed that humans and nonhuman animals can organize behavior using different scaling principles. To deal with increases in linear distance, isochrony suggest that there is a corresponding increase in speed, whereas to deal with changes in curvature, speed is adjusted according to a power function. The present study investigates whether these principles provide a framework for describing the organization of mouse behavior in a variety of standard experimental tasks. The structure of movement was examined in ambulation during open field exploration; manipulation in a string-pulling task, in which a string is advanced hand over hand to retrieve food; and rung-walking, in which the limbs successively step from rung to rung on a horizontal ladder. Both principles were found to be conserved in the organization of mouse behavior across scales of movement. These principles provide novel measures of the temporal and geometric features of movement in the mouse and insights into how the temporal and geometric features of movement are conserved within different species.
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Conducta Exploratoria , Animales , Ratones , Masculino , Conducta Exploratoria/fisiología , Ratones Endogámicos C57BL , Movimiento/fisiología , Actividad Motora/fisiología , Locomoción/fisiología , Conducta Animal/fisiología , Caminata/fisiologíaRESUMEN
Zebrafish (Danio rerio) is ideal for studying the effects of toxins like lead or plumbum (Pb) which persist in the environment and harm body systems when absorbed. Increasing Pb concentration could result in a higher mortality rate and alteration of behavior and metabolism. The present study evaluates the acute toxicity effect of Pb on metabolome and behavior in adult zebrafish. The zebrafish were exposed to various Pb concentrations ranging from 0 to 30 mg/L for different periods (24, 48, and 72 h) before the fish samples were subjected to Nuclear Magnetic Resonance (NMR)-multivariate data analysis (MVDA) with additional support from behavioral assessment. The behavior of zebrafish was significantly altered after Pb inducement and the differential metabolites increased in low (5 mg/L) while decreased in high (10 mg/L) Pb concentrations. An ideal Pb induction could be achieved by 5 mg/L concentration in 24 h, which induced significant metabolite changes without irreversible damage. Continuing research on the effects of lead toxicity is crucial to develop effective prevention and treatment strategies.
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Conducta Animal , Relación Dosis-Respuesta a Droga , Plomo , Metabolómica , Pez Cebra , Animales , Plomo/toxicidad , Conducta Animal/efectos de los fármacos , Pruebas de Toxicidad Aguda , Espectroscopía de Protones por Resonancia Magnética , Contaminantes Químicos del Agua/toxicidad , Metaboloma/efectos de los fármacos , Factores de Tiempo , MasculinoRESUMEN
BACKGROUND: Anxiety is an adaptive response to potentially threatening conditions. Excessive and uncontrolled anxiety responses become nonadaptive and cause anxiety disorders. To better understand the anxiety-modulating effects of Mg sulfate, behavioral test batteries in the assessment of anxiety and learning and memory functions were performed simultaneously over a time period. This study also examines the effects of Mg sulfate compared to diazepam, an anxiolytic drug with amnestic effects on anxiety-like behavior, as well as possible oxidative-nitrosative stress and hippocampal changes in male rats exposed to predator odor. METHODS: Young adult Sprague-Dawley male rats were used. The rats were assessed using a comprehensive neurobehavioral test battery consisting of novel object recognition, open field, and successive alleys tasks. Anxiety was induced by cat odor, and diazepam and Mg were used as study drugs. Of the frontal cortex and hippocampus, the state of total oxidant and antioxidant and NO levels and histological examination of hippocampal CA1, CA2, CA3, and DG regions were performed. RESULTS: Diazepam- and Mg-treated rats showed an improvement in anxiety-related behavior to predator odors. Furthermore, Mg treatment alleviated some of the increasing oxidative stress in the frontal cortex and hippocampus of rats, while diazepam treatment in particular enhanced hippocampal oxidant and antioxidant activity. In addition, brain NO increase induced by animal odor exposure or diazepam treatment was ameliorated by Mg administration. CONCLUSIONS: Overall, our work suggests that Mg had a partial anxiolytic effect on anxiety-like behaviors, although not as much as diazepam, and this effect varied depending on the dose. Mg treatment might counteract increased oxidative stress and elevated NO levels in the brain.
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Ansiolíticos , Ansiedad , Diazepam , Modelos Animales de Enfermedad , Sulfato de Magnesio , Ratas Sprague-Dawley , Animales , Masculino , Ansiedad/tratamiento farmacológico , Diazepam/farmacología , Ansiolíticos/farmacología , Ansiolíticos/uso terapéutico , Sulfato de Magnesio/farmacología , Hipocampo/efectos de los fármacos , Hipocampo/metabolismo , Estrés Oxidativo/efectos de los fármacos , Ratas , Memoria/efectos de los fármacos , Óxido Nítrico/metabolismo , OdorantesRESUMEN
Introduction: Low back pain is the most common type of chronic pain. We examined pain-related behaviors across 18 weeks in rats that received injury to one or two lumbar intervertebral discs (IVD) to determine if multi-level disc injuries enhance/prolong pain. Methods: Twenty-three Sprague-Dawley adult female rats were used: 8 received disc puncture (DP) of one lumbar IVD (L5/6, DP-1); 8 received DP of two lumbar IVDs (L4/5 & L5/6, DP-2); 8 underwent sham surgery. Results: DP-2 rats showed local (low back) sensitivity to pressure at 6- and 12-weeks post-injury, and remote sensitivity to pressure (upper thighs) at 12- and 18-weeks and touch (hind paws) at 6, 12 and 18-weeks. DP-1 rats showed local and remote pressure sensitivity at 12-weeks only (and no tactile sensitivity), relative to Sham DP rats. Both DP groups showed reduced distance traveled during gait testing over multiple weeks, compared to pre-injury; only DP-2 rats showed reduced distance relative to Sham DP rats at 12-weeks. DP-2 rats displayed reduced positive interactions with a novel adult female rat at 3-weeks and hesitation and freezing during gait assays from 6-weeks onwards. At study end (18-weeks), radiological and histological analyses revealed reduced disc height and degeneration of punctured IVDs. Serum BDNF and TNFα levels were higher at 18-weeks in DP-2 rats, relative to Sham DP rats, and levels correlated positively with remote sensitivity in hind paws (tactile) and thighs (pressure). Discussion: Thus, multi-level disc injuries resulted in earlier, prolonged and greater discomfort locally and remotely, than single-level disc injury. BDNF and TNFα may have contributing roles.
RESUMEN
BACKGROUND: Huntington disease (HD) is a neurodegenerative disorder with complex motor and behavioural manifestations. The Q175 knock-in mouse model of HD has gained recent popularity as a genetically accurate model of the human disease. However, behavioural phenotypes are often subtle and progress slowly in this model. Here, we have implemented machine-learning algorithms to investigate behaviour in the Q175 model and compare differences between sexes and disease stages. We explore distinct behavioural patterns and motor functions in open field, rotarod, water T-maze, and home cage lever-pulling tasks. RESULTS: In the open field, we observed habituation deficits in two versions of the Q175 model (zQ175dn and Q175FDN, on two different background strains), and using B-SOiD, an advanced machine learning approach, we found altered performance of rearing in male manifest zQ175dn mice. Notably, we found that weight had a considerable effect on performance of accelerating rotarod and water T-maze tasks and controlled for this by normalizing for weight. Manifest zQ175dn mice displayed a deficit in accelerating rotarod (after weight normalization), as well as changes to paw kinematics specific to males. Our water T-maze experiments revealed response learning deficits in manifest zQ175dn mice and reversal learning deficits in premanifest male zQ175dn mice; further analysis using PyMouseTracks software allowed us to characterize new behavioural features in this task, including time at decision point and number of accelerations. In a home cage-based lever-pulling assessment, we found significant learning deficits in male manifest zQ175dn mice. A subset of mice also underwent electrophysiology slice experiments, revealing a reduced spontaneous excitatory event frequency in male manifest zQ175dn mice. CONCLUSIONS: Our study uncovered several behavioural changes in Q175 mice that differed by sex, age, and strain. Our results highlight the impact of weight and experimental protocol on behavioural results, and the utility of machine learning tools to examine behaviour in more detailed ways than was previously possible. Specifically, this work provides the field with an updated overview of behavioural impairments in this model of HD, as well as novel techniques for dissecting behaviour in the open field, accelerating rotarod, and T-maze tasks.