RESUMO
BACKGROUNDS: Impaired sleep is independent risk factor of neurodegeneration and dementia. Chronic insomnia impairs melatonin (MEL) production that is directly proportionate to its duration. The underlying mechanisms linking sleep loss to dementia and the possible therapeutic effect of melatonin have not been fully elucidated. Previous research showed great controversy concerning the effects of paradoxical sleep deprivation (PSD) on body weight, serum lipoproteins, and inflammatory cytokines. GOALS: To examine the effect of chronic paradoxical sleep deprivation (PSD) with and without MEL supplementation on memory using RAWM, parameters of metabolic syndrome (MS), liver enzymes, serum cortisol, and inflammatory cytokines as well as liver, colon, and brain histopathology. METHODS: Forty rats were divided into four groups ten animals each; C: control, G: grid group, SD: sleep deprivation group, and SD+MEL sleep deprivation treated with melatonin. RESULTS: MEL supplementation reversed PSD-induced memory deficits (P<0.05), the elevation of serum cortisol (P<0.001), glucose (P<0.05), ALT (P<0.05), AST (P<0.001), TNF-alpha (P<0.001), IL-10 (P<0.01) and improved colon, liver, and brain architecture. Melatonin reduced body weight (P<0.05), total cholesterol, LDL-c, and triglycerides as well as increased HDL-c (P<0.001). CONCLUSION: MEL has a protective effect against chronic PSD-induced metabolic malfunction and cognitive deterioration by reducing stress, improving immunity, and maintaining colonic wall integrity.
RESUMO
The current study investigated the role of epigenetic dysregulation of brain derived neurotrophic factor (BDNF) and glial fibrillary acidic protein (GFAP) genes and oxidative stress as possible mechanisms of autistic-like behaviors in neonatal isolation model in rats and the impact of folic acid administration on these parameters. Forty Wistar albino pups were used as follows: control, folic acid administered, isolated, and isolated folic acid treated groups. Isolated pups were separated from their mothers for 90 min daily from postnatal day (PND) 1 to 11. Pups (isolated or control) received either the vehicle or folic acid (4 mg/kg/day) orally from PND 1 to 29. Behavioral tests were done from PND 30 to 35. Oxidative stress markers and antioxidant defense in the frontal cortex homogenate were determined. DNA methylation of BDNF and GFAP genes was determined by qPCR. Histopathological examination was carried out. Neonatal isolation produced autistic-like behaviors that were associated with BDNF and GFAP hypomethylation, increased oxidative stress, increased inflammatory cell infiltration, and structural changes in the frontal cortex. Folic acid administration concurrently with isolation reduced neonatal isolation-induced autistic-like behaviors, decreased oxidative stress, regained BDNF and GFAP gene methylation, and ameliorated structural changes in the frontal cortices of isolated folic acid treated rats. Novelty: Neonatal isolation induces "autistic-like" behavior and these behaviors are reversed by folic acid supplementation. Neonatal isolation induces DNA hypomethylation of BDNF and GFAP, increased oxidative stress markers, and neuroinflammation. All of these changes were reversed by daily folic acid supplementation.