title: Effects of enriched environment on alterations in the prefrontal cortex GFAP- and S100B-immunopositive astrocytes and behavioral deficits in MK-801-treated rats.
abstract: A plethora of studies have indicated that enriched environment (EE) paradigm provokes plastic and morphological changes in astrocytes with accompanying increments of their density and positively affects the behavior of rodents. We also previously documented that EE could be employed to preclude several behavioral abnormalities, mainly cognitive deficits, attributed to postnatal N-methyl-d-aspartate (NMDA) receptor antagonist (MK-801) treatment, as a rodent model of schizophrenia (SCH) aspects. Given this, the current study quantitatively investigated the number of cells, presumed to be astrocytes, expressing two astroglia-associated proteins (S100B and glial fibrillary acidic protein (GFAP)) by immunohistochemistry in the prefrontal cortex (PFC), along with anxiety and passive avoidance (PA) learning behaviors by utilizing elevated plus maze (EPM) and shuttle-box tests, in MK-801-treated male wistar rats submitted to EE and non-EE rats. Following a treatment regime of sub-chronic MK-801 (1.0mg/kg i.p. daily for five consecutive days from postnatal day (P) 6), S-100B-positive cells and anxiety level were markedly increased, while the GFAP-positive cells and PA learning were notably attenuated. The trend of diminished GFAP-immunopositive cells and elevated S100B-immunostained cells in the PFC was reversed in the SCH-like rats by exposure of animals to EE, commencing from birth up to the time of experiments on P28-85. Additionally, EE exhibited an ameliorating effect on the behavioral abnormalities evoked by MK-801. Overall, present findings support that improper astrocyte functioning and behavioral changes, reminiscent of the many facets of SCH, occur consequential to repetitive administration of MK-801 and that raising rat pups in an EE mitigates these alterations.
authors.affiliation: Department of Anatomical Sciences, Afzalipour School of Medicine, Kerman University of Medical Sciences, Kerman, Iran; Neuroscience Research Center, Neuropharmacology Institute, Kerman University of Medical Sciences, Kerman, Iran.
authors.forename: M
authors.initials: M
authors.lastname: Rahati
authors.affiliation: Department of Physiology, Afzalipour School of Medicine, Kerman University of Medical Sciences, Kerman, Iran.
authors.forename: M
authors.initials: M
authors.lastname: Nozari
authors.affiliation: Department of Pharmacology, Molecular Medicine Research Center, Hormozgan University of Medical Sciences, Bandar Abbas, Iran.
authors.forename: H
authors.initials: H
authors.lastname: Eslami
authors.affiliation: Neuroscience Research Center, Neuropharmacology Institute, Kerman University of Medical Sciences, Kerman, Iran.
authors.forename: M
authors.initials: M
authors.lastname: Shabani
authors.affiliation: Department of Anatomical Sciences, Afzalipour School of Medicine, Kerman University of Medical Sciences, Kerman, Iran; Neuroscience Research Center, Neuropharmacology Institute, Kerman University of Medical Sciences, Kerman, Iran. Electronic address: m_basiri@kmu.ac.ir.
authors.forename: M
authors.initials: M
authors.lastname: Basiri
mesh_terms: D000818:Animals; D001007:Anxiety / Q000139:chemically induced / Q000517:prevention & control*; D001253:Astrocytes / Q000187:drug effects / Q000378:metabolism*; D001362:Avoidance Learning / Q000187:drug effects; D016291:Dizocilpine Maleate / Q000008:administration & dosage*; D004777:Environment; D018691:Excitatory Amino Acid Antagonists / Q000008:administration & dosage*; D005904:Glial Fibrillary Acidic Protein / Q000378:metabolism; D008124:Locomotion / Q000187:drug effects; D008297:Male; D008569:Memory Disorders / Q000139:chemically induced / Q000517:prevention & control*; D017397:Prefrontal Cortex / Q000187:drug effects / Q000378:metabolism*; D051381:Rats; D017208:Rats, Wistar; D064568:S100 Calcium Binding Protein beta Subunit / Q000378:metabolism
chemical_list: D018691:Excitatory Amino Acid Antagonists; C000614142:Gfap protein, rat; D005904:Glial Fibrillary Acidic Protein; D064568:S100 Calcium Binding Protein beta Subunit; C579158:S100b protein, rat; D016291:Dizocilpine Maleate
keywords: GFAP; MK-801; S100B; astrocyte; environmental enrichment; schizophrenia