title: Environmental enrichment ameliorates chronic immobilisation stress-induced spatial learning deficits and restores the expression of BDNF, VEGF, GFAP and glucocorticoid receptors.
abstract: Severe and prolonged stress is the main environmental factor that precipitates depression, anxiety and cognitive dysfunctions. On the other hand, exposure to environmental enrichment (EE) has been shown to induce progressive plasticity in the brain and improve learning and memory in various neurological and psychiatric disorders. It is not known whether exposure to enriched environment could ameliorate chronic immobilisation stress-induced cognitive deficits and altered molecular markers. Hence, in the present study we aimed to evaluate the effect of enriched environment on chronic immobilisation stress (CIS) associated changes in spatial learning and memory, behavioural measures of anxiety, depression and molecular markers as well as structural alterations. Male Wistar rats were subjected to chronic immobilisation stress for 2h/day/10days followed by 2weeks of exposure to EE. CIS resulted in weight loss, anhedonia, increased immobility, spatial learning and memory impairment, enhanced anxiety, and reduced expression of BDNF, VEGF, GFAP and glucocorticoid receptors (GR) in discrete brain regions. Interestingly, stressed rats exposed to enrichment ameliorated behavioural depression, spatial learning and memory impairment and reduced anxiety behaviour. In addition, EE restored BDNF, VEGF, GFAP and GR expression and normalized hypotrophy of dentate gyrus and hippocampus in CIS rats. In contrast, EE did not restore hypertrophy of the amygdalar complex. Thus, EE ameliorates stress-induced cognitive deficits by modulating the neurotrophic factors, astrocytes and glucocorticoid receptors in the hippocampus, frontal cortex and amygdala.
authors.affiliation: Department of Neurophysiology, National Institute of Mental Health and Neuro Sciences, Hosur Road, Bengaluru 560 029, India.
authors.forename: B M
authors.initials: BM
authors.lastname: Shilpa
authors.affiliation: Department of Neurophysiology, National Institute of Mental Health and Neuro Sciences, Hosur Road, Bengaluru 560 029, India.
authors.forename: V
authors.initials: V
authors.lastname: Bhagya
authors.affiliation: Department of Neurochemistry, National Institute of Mental Health and Neuro Sciences, Hosur Road, Bengaluru 560 029, India.
authors.forename: G
authors.initials: G
authors.lastname: Harish
authors.affiliation: Department of Neurochemistry, National Institute of Mental Health and Neuro Sciences, Hosur Road, Bengaluru 560 029, India.
authors.forename: M M
authors.initials: MM
authors.lastname: Srinivas Bharath
authors.affiliation: Department of Neurophysiology, National Institute of Mental Health and Neuro Sciences, Hosur Road, Bengaluru 560 029, India. Electronic address: bssrao.nimhans@gmail.com.
authors.forename: B S
authors.initials: BS
authors.lastname: Shankaranarayana Rao
mesh_terms: D000818:Animals; D001007:Anxiety / Q000209:etiology / Q000628:therapy*; D019208:Brain-Derived Neurotrophic Factor / Q000378:metabolism*; D060825:Cognitive Dysfunction / Q000209:etiology / Q000628:therapy*; D003863:Depression / Q000209:etiology / Q000628:therapy*; D004195:Disease Models, Animal; D004777:Environment; D005904:Glial Fibrillary Acidic Protein / Q000378:metabolism*; D006624:Hippocampus / Q000378:metabolism / Q000473:pathology; D008297:Male; D008569:Memory Disorders / Q000209:etiology / Q000628:therapy*; D051381:Rats; D017208:Rats, Wistar; D011965:Receptors, Glucocorticoid / Q000378:metabolism*; D012149:Restraint, Physical; D065853:Spatial Learning / Q000502:physiology*; D013315:Stress, Psychological / Q000150:complications* / Q000209:etiology; D042461:Vascular Endothelial Growth Factor A / Q000378:metabolism*
chemical_list: D019208:Brain-Derived Neurotrophic Factor; C000614142:Gfap protein, rat; D005904:Glial Fibrillary Acidic Protein; D011965:Receptors, Glucocorticoid; D042461:Vascular Endothelial Growth Factor A; C467498:vascular endothelial growth factor A, rat
keywords: Amygdalar complex; Chronic immobilisation stress; Depression; Enriched environment; Glucocorticoid receptors; Hippocampus; Neurotrophic factors; Structural plasticity