Sudhanshu Sekhar Sahu

Neuroprotective effect of resveratrol against prenatal stress induced cognitive impairment and possible involvement of Na+, K+-ATPase activity

Resveratrol, an active ingredient of red wine extracts, has been shown to exhibit neuroprotective effects in several experimental models. Hence in the present study, the protective effects of resveratrol on cognitive deficits induced by prenatal stress were evaluated in offspring, and the possible involvement of Na(+), K(+)-ATPase in learning deficits were explored. Pregnant rats were subjected to restraint stress during early or late gestational period. Another set of rats received resveratrol during the entire gestational period along with early or late gestational stress. The study parameters included various behavioral tests like open field test and Morris water maze test. At the end of the behavioral tests (on 40th postnatal day), the offspring were sacrificed, and their brain homogenate was subjected to Na(+), K(+)-ATPase estimation. Early and late gestational stress affected spatial learning and memory and prenatal resveratrol has reversed these cognitive deficits. The Na(+), K(+)-ATPase activity in the offspring brain homogenate was reduced in the late gestational stress group; however prenatal resveratrol treatment has not affected this activity. These data suggest the neuroprotective efficacy of resveratrol against prenatal stress induced cognitive impairment. Though late gestational stress involves Na(+), K(+)-ATPase activity in rat brain homogenate, this would not be the primary cause in prenatal stress-induced cognitive dysfunction.

Resveratrol for Prenatal-Stress-Induced oxidative damage in growing brain and its consequences on survival of neurons

Abstract Background: Prenatal-stress-induced neuronal damage in offspring is multifactorial, including oxidative damage in the developing brain. Resveratrol is known to exert its neuroprotective potentials by upregulating several antioxidant systems. Hence, the study was undertaken to evaluate the neuroprotective effect of resveratrol against prenatal-stress-induced hippocampal damage and oxidative damage in neonate rat brains. Methods: Pregnant rats were subjected to restraint stress during early or late gestational period. Another set of rats received resveratrol during the entire gestational period along with early or late gestational stress. The study parameters included several antioxidant studies directly from rat brain homogenate on the 40th postnatal day and hippocampal neuronal assay on the 21st postnatal day. Results: Early as well as late gestational stress resulted in a significant increase in lipid peroxidation and advanced oxidation protein products and decrease in total antioxidant activity and nitric oxide levels in rat brain homogenate. The neurons of the dentate gyrus were severely affected in early and late gestational stress, and only the neurons of the CA3 region were adversely affected in late gestational stress. Administration of resveratrol reversed the prenatal-stress-induced oxidative damage and neurons of dentate gyrus but not the CA3 hippocampal neurons. Conclusions: These results show the neuroprotective abilities of resveratrol against prenatal-stress-induced oxidative damage in neonatal rat brain.

Effect of prenatal stress on expression of glutathione system in neonatal rat brain.

AIM Prenatal stress is known to adversely affect the fetal brain development and also neuronal loss. The mechanism(s) associated with prenatal stress induced developmental neurotoxicity remains obscure. Few studies point to the glutathione (GSH) antioxidant system which is an important molecular target for this toxicant. Hence the present study investigates the effect of prenatal stress on glutathione system in neonatal rat brain. MATERIAL AND METHODS Three to four months old pregnant Wistar rats were subjected to restraint stress during early or late gestational period. The offspring were sacrificed on 40th day and their brain homogenate was subjected to antioxidant studies. The serum corticosterone and adrenal ascorbic acid levels were also estimated from offspring. RESULTS The prenatal stress has resulted in an increase in the serum corticosterone and reduced adrenal ascorbic acid levels in neonatal pups. Prenatal stress during early or late gestation life showed reduced glutathione, glutathione reductase (GSSG-Rd) and superoxide dismutase (SOD) activity in offspring brain homogenate. CONCLUSION These data suggest that stress during early or late gestation period affect glutathione system in developing neonatal rat brain, which is associated with elevated serum corticosterone and reduced adrenal ascorbic acid levels.

A Comparison of Resveratrol and Vitamin C Therapy on Expression of BDNF in Stressed Rat Brain Homogenate

Prolonged exposure to stress results in neuronal loss, which is associated with depletion of Brain derived neurotrophic factor (BDNF) in rat brain. Resveratrol, an antioxidant is known to exert neuroprotective effect in both human and animal models. Vitamin C too has important anti-oxidant properties, and protects cells against oxidative stress. In the present study we have evaluated the effect of resveratrol and vitamin C on BDNF expression in stressed rat brain homogenate. Rats were treated with 10 or 20mg/kg body weight dose of resveratrol and 100 or 200mg/kg body weight dose of vitamin C for a period of 28 days, beginning one week prior to stress treatment (restraint stress for 6 hours daily for 21 days). Rats were sacrificed after stress treatment and the whole brain BDNF level was estimated using enzyme-linked immunosorbent assay (ELISA) kit. Our study confirms the neuroprotective effects of resveratrol by enhanced BDNF level in stressed rats. Though vitamin C has enhanced the BDNF expression in stressed rats interestingly it had an adverse effect when treated alone.

Phenelzine, a cell adhesion molecule L1 mimetic small organic compound, promotes functional recovery and axonal regrowth in spinal cord-injured zebrafish

&NA; Injury to the spinal cord initiates a cascade of cellular and molecular events that contribute to the tissue environment that is non‐permissive for cell survival and axonal regrowth/sprouting in the adult mammalian central nervous system. The endogenous repair response is impaired in this generally inhibitory environment. Previous studies indicate that homophilic interactions of the neural cell adhesion molecule L1 (L1CAM) promote recovery after spinal cord injury and ameliorate neurodegenerative processes in experimental rodent and zebrafish models. In light of reports that phenelzine, a small organic compound that mimics L1, stimulates neuronal survival, neuronal migration, neurite outgrowth, and Schwann cell proliferation in vitro in a L1‐dependent manner, we examined the restorative potential of phenelzine in a zebrafish model of spinal cord injury. Addition of phenelzine into the aquarium water immediately after spinal cord injury accelerated locomotor recovery and promoted axonal regrowth and remyelination in larval and adult zebrafish. Phenelzine treatment up‐regulated the expression and proteolysis of L1.1 (a homolog of the mammalian recognition molecule L1) and phosphorylation of Erk in the spinal cord caudal to lesion site. By combining the results of the present study with those of other studies, we propose that phenelzine bears hopes for therapy of nervous system injuries. HighlightsPS treatment accelerates functional recovery after spinal cord injury in zebrafish.PS treatment leads to upregulation of L1 expression in the severed spinal cord.PS treatment promotes axonal regrowth and remyelination.PS treatment stimulates Erk phosphorylation. Abbreviations: CNS: central nervous system; dpf: days post fertilization; GAPDH: glyceraldehyde 3‐phosphate dehydrogenase; MBP: myelin basic protein; MS‐222: ethyl 3‐aminobenzoate methanesulfonate; PS: phenelzine sulfate; PBS: phosphate‐buffered saline, pH 7.3; SCI: spinal cord injury.

Effect of Prenatal Isotretinoin on Postnatal Development of Cornea and Lens in Albino Wistar Rat: A Morphometric and Histopathlogical Analysis

Isotretinoin is a known teratogen affecting the neuronal differentiation in developing brain. Apart from its effects on brain and other craniofacial malformations, it is also known to cause failure of detachment of the lens from the surface ectoderm. Interestingly very little is known about the teratogenic effect of isotretinoin on the development of eye. Hence in the present study we evaluated the morphometric and histopathological changes in developing cornea and lens in rats during postnatal development.The pregnant rats received16mg/kg dose of isotretinoin during gestation day 1to 7 or 12 to 18. The control group received equivalent volume of vegetable oil instead of isotretinoin. The pups were sacrificed on day 7 or 14 or 30 for histopathological and morphometric analysis using haematoxylin and eosin staining.The results of the study clearly demonstrate that prenatal isotretinoin severely affects the development and growth of the cornea in both treatment regimes. There was also a considerable damage to the morphology of the lens.This preliminary animal study clearly demonstrates the teratogenic effect of isotretinoin on developing cornea and lens.