RESUMEN
Type 1 diabetes mellitus (T1DM) progressively affects cognitive domains, increases blood-brain barrier (BBB) permeability and promotes neurovascular impairment in specific brain areas. Physical exercise, on the other hand, has beneficial effects on brain functions, improving learning and memory. This study investigated the effects of treadmill training on cognitive and motor behavior, and on the expression of proteins related to BBB integrity, such as claudin-5 and aquaporin-4 (AQP4) in the hippocampus and striatum in diabetic rats. For this study, 60 Wistar rats were divided into four groups (n=15 per group): non-trained control (NTC), trained control (TC), non-trained diabetic (NTD), trained diabetic (TD). After diabetic induction of 30 days by streptozotocin injection, the exercise groups were submitted to 5 weeks of running training. After that, all groups were assessed in a novel object-recognition task (NOR) and the rotarod test. Additionally, claudin-5 and AQP4 levels were measured using biochemical assays. The results showed that exercise enhanced NOR task performance and rotarod ability in the TC and TD animals. Diabetes produced a decrease in claudin-5 expression in the hippocampus and striatum and reduced AQP4 in the hippocampus. Exercise preserved the claudin-5 content in the striatum of TD rats, but not in the hippocampus. The reduction of AQP4 levels produced by diabetes was not reversed by exercise. We conclude that exercise improves short-term memory retention, enhances motor performance in diabetic rats and affects important structural components of the striatal BBB. The results obtained could enhance the knowledge regarding the neurochemical benefits of exercise in diabetes.
Asunto(s)
Barrera Hematoencefálica/fisiopatología , Diabetes Mellitus Experimental , Trastornos de la Memoria/rehabilitación , Destreza Motora/fisiología , Condicionamiento Físico Animal/métodos , Análisis de Varianza , Animales , Acuaporina 4/metabolismo , Glucemia/efectos de los fármacos , Barrera Hematoencefálica/efectos de los fármacos , Peso Corporal/efectos de los fármacos , Claudina-5/metabolismo , Diabetes Mellitus Experimental/inducido químicamente , Diabetes Mellitus Experimental/complicaciones , Diabetes Mellitus Experimental/terapia , Prueba de Esfuerzo , Conducta Exploratoria/fisiología , Masculino , Ratas , Ratas Wistar , Tiempo de Reacción/efectos de los fármacos , Tiempo de Reacción/fisiología , Reconocimiento en Psicología/fisiología , Estreptozocina/toxicidadRESUMEN
AIMS: We investigated the effects of ketogenic diet (KD) on levels of tumor necrosis factor alpha (TNF-α, a classical pro-inflammatory cytokine), BDNF (brain-derived neurotrophic factor, commonly associated with synaptic plasticity), and S100B, an astrocyte neurotrophic cytokine involved in metabolism regulation. MAIN METHODS: Young Wistar rats were fed during 8weeks with control diet or two KD, containing different proportions of omega 6 and omega 3 polyunsaturated fatty acids. Contents of TNF-α, BDNF and S100B were measured by ELISA in two brain regions (hippocampus and striatum) as well as blood serum and cerebrospinal fluid. KEY FINDINGS: Our data suggest that KD was able to reduce the levels of BDNF in the striatum (but not in hippocampus) and S100B in the cerebrospinal fluid of rats. These alterations were not affected by the proportion of polyunsaturated fatty acids offered. No changes in S100B content were observed in serum or analyzed brain regions. Basal TNF-α content was not affected by KD. SIGNIFICANCE: These findings reinforce the importance of this diet as an inductor of alterations in the brain, and such changes might contribute to the understanding of the effects (and side effects) of KD in brain disorders.
Asunto(s)
Factor Neurotrófico Derivado del Encéfalo/metabolismo , Dieta Cetogénica , Factores de Crecimiento Nervioso/metabolismo , Proteínas S100/metabolismo , Factor de Necrosis Tumoral alfa/metabolismo , Animales , Cuerpo Estriado/metabolismo , Ensayo de Inmunoadsorción Enzimática , Ácidos Grasos Omega-3/administración & dosificación , Ácidos Grasos Omega-6/administración & dosificación , Hipocampo/metabolismo , Masculino , Ratas , Ratas Wistar , Subunidad beta de la Proteína de Unión al Calcio S100RESUMEN
Physical exercise effects on brain health and cognitive performance have been described. Synaptic remodeling in hippocampus induced by physical exercise has been described in animal models, but the underlying mechanisms remain poorly understood. Changes in astrocytes, the glial cells involved in synaptic remodeling, need more characterization. We investigated the effect of moderate treadmill exercise (20 min/day) for 4 weeks on some parameters of astrocytic activity in rat hippocampal slices, namely, glial fibrillary acidic protein (GFAP), glutamate uptake and glutamine synthetase (GS) activities, glutathione content, and S100B protein content and secretion, as well as brain-derived neurotrophic factor (BDNF) levels and glucose uptake activity in this tissue. Results show that moderate treadmill exercise was able to induce a decrease in GFAP content (evaluated by ELISA and immunohistochemistry) and an increase in GS activity. These changes could be mediated by corticosterone, whose levels were elevated in serum. BDNF, another putative mediator, was not altered in hippocampal tissue. Moreover, treadmill exercise caused a decrease in NO content. Our data indicate specific changes in astrocyte markers induced by physical exercise, the importance of studying astrocytes for understanding brain plasticity, as well as reinforce the relevance of physical exercise as a neuroprotective strategy.
Asunto(s)
Astrocitos/fisiología , Prueba de Esfuerzo/métodos , Hipocampo/citología , Hipocampo/fisiología , Condicionamiento Físico Animal/métodos , Animales , Corticosterona/sangre , Masculino , Ratas , Ratas WistarRESUMEN
Alzheimer's disease (AD) is the most prevalent form of dementia. Intracerebroventricular (ICV) infusion of streptozotocin (STZ) provides a relevant animal model of chronic brain dysfunction that is characterized by long-term and progressive deficits in learning, memory, and cognitive behavior, along with a permanent and ongoing cerebral energy deficit. Numerous studies on green tea epigallocatechin gallate (EGCG) demonstrate its beneficial effects on cognition and memory. As such, this study evaluated, for the first time, the effects of sub-chronic EGCG treatment in rats that were submitted to ICV infusion of STZ (3mg/kg). Male Wistar rats were divided into sham, STZ, sham+EGCG and STZ+EGCG groups. EGCG was administered at a dose of 10mg/kg/day for 4 weeks per gavage. Learning and memory was evaluated using Morris' Water Maze. Oxidative stress markers and involvement of the nitric oxide (NO) system, acetylcholinesterase activity (AChE) and glucose uptake were evaluated as well as glial parameters including S100B content and secretion and GFAP content. Our results show that EGCG was not able to modify glucose uptake and glutathione content, although cognitive deficit, S100B content and secretion, AChE activity, glutathione peroxidase activity, NO metabolites, and reactive oxygen species content were completely reversed by EGCG administration, confirming the neuroprotective potential of this compound. These findings contribute to the understanding of diseases accompanied by cognitive deficits and the STZ-model of dementia.
Asunto(s)
Acetilcolinesterasa/metabolismo , Antibióticos Antineoplásicos , Antioxidantes/farmacología , Catequina/análogos & derivados , Demencia/inducido químicamente , Demencia/metabolismo , Fármacos Neuroprotectores , Estrés Oxidativo/efectos de los fármacos , Estreptozocina , Té/química , Animales , Antibióticos Antineoplásicos/administración & dosificación , Catequina/farmacología , Cognición/efectos de los fármacos , Proteína Ácida Fibrilar de la Glía/metabolismo , Glucosa/metabolismo , Glutatión/metabolismo , Glutatión Peroxidasa/metabolismo , Hipocampo/efectos de los fármacos , Hipocampo/metabolismo , Inyecciones Intraventriculares , Masculino , Aprendizaje por Laberinto/efectos de los fármacos , Factores de Crecimiento Nervioso/metabolismo , Neuroglía/metabolismo , Óxido Nítrico/metabolismo , Ratas , Ratas Wistar , Especies Reactivas de Oxígeno/metabolismo , Subunidad beta de la Proteína de Unión al Calcio S100 , Proteínas S100/metabolismo , Percepción Espacial/efectos de los fármacos , Estreptozocina/administración & dosificaciónRESUMEN
Several types of animal models have been developed to investigate Alzheimer's disease (AD). Okadaic acid (OA), a potent inhibitor of phosphatases 1 and 2A, induces characteristics that resemble AD-like pathology. Memory impairment induced by intra-hippocampal injection of OA has been reported, accompanied by remarkable neuropathological changes including hippocampal neurodegeneration, a paired helical filament-like phosphorylation of tau protein, and formation of ß-amyloid containing plaque-like structures. Rats were submitted to bilateral intrahippocampal okadaic acid-injection (100 ng) and, 12 days after the surgery, behavioral and biochemical tests were performed. Using this model, we evaluated spatial cognitive deficit and neuroglial alterations, particularly astroglial protein markers such as glial fibrillary acidic protein (GFAP) and S100B, metabolism of glutamate, oxidative parameters and alterations in MAPKs. Our results indicate significant hippocampal changes, including increased GFAP, protein oxidation, and phosphorylation of p38(MAPK); and decreases in glutathione content, transporter EAAT2/GLT-1, and glutamine synthetase activity as well as a decrease in cerebrospinal fluid S100B. No alterations were observed in glutamate uptake activity and S100B content. In conclusion, the OA-induced model of dementia caused spatial cognitive deficit and oxidative stress in this model and, for the first time to our knowledge, specific astroglial alterations. Findings contribute to understanding diseases accompanied by cognitive deficits and the neural damage induced by AO administration.