title: Reversal of reduced parvalbumin neurons in hippocampus and amygdala of Angelman syndrome model mice by chronic treatment of fluoxetine.
abstract: Angelman syndrome (AS) is a neuropsychiatric disorder characterized by autism, intellectual disability and motor disturbances. The disease is primarily caused by the loss of function of maternally inherited UBE3A. Ube3a maternal-deficient mice recapitulates many essential feature of AS. These AS mice have been shown to be under chronic stress and exhibits anxiety-like behaviour because of defective glucocorticoid receptor signalling. Here, we demonstrate that chronic stress in these mice could lead to down-regulation of parvalbumin-positive interneurons in the hippocampus and basolateral amygdala from early post-natal days. Down-regulation of parvalbumin-positive interneurons number could be because of decrease in the expression of parvalbumin in these neurons. We also find that treatment with fluoxetine, a selective serotonin reuptake inhibitor, results in restoration of impaired glucocorticoid signalling, elevated serum corticosterone level, parvalbumin-positive interneurons and anxiety-like behaviours. Our findings suggest that impaired glucocorticod signalling in hippocampus and amygdala of AS mice is critical for the decrease in parvalbumin interneurons number, emergence of anxiety and other behavioural deficits and highlights the importance of fluoxetine in the recovery of these abnormalities.
authors.affiliation: Cellular and Molecular Neuroscience Laboratory, National Brain Research Centre, Manesar, Gurgaon, India.
authors.forename: Swetha K
authors.initials: SK
authors.lastname: Godavarthi
authors.forename: Ankit
authors.initials: A
authors.lastname: Sharma
authors.forename: Nihar Ranjan
authors.initials: NR
authors.lastname: Jana
mesh_terms: D000679:Amygdala / Q000187:drug effects / Q000473:pathology*; D017204:Angelman Syndrome / Q000188:drug therapy* / Q000473:pathology* / Q000523:psychology; D000818:Animals; D001522:Behavior, Animal / Q000187:drug effects; D015153:Blotting, Western; D002452:Cell Count; D015536:Down-Regulation / Q000187:drug effects; D005106:Exploratory Behavior / Q000187:drug effects / Q000502:physiology; D005473:Fluoxetine / Q000627:therapeutic use*; D006624:Hippocampus / Q000187:drug effects / Q000473:pathology*; D007150:Immunohistochemistry; D007395:Interneurons / Q000187:drug effects; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D009474:Neurons / Q000187:drug effects / Q000473:pathology*; D010320:Parvalbumins / Q000187:drug effects / Q000502:physiology*; D060888:Real-Time Polymerase Chain Reaction; D011965:Receptors, Glucocorticoid / Q000187:drug effects; D017367:Selective Serotonin Reuptake Inhibitors / Q000627:therapeutic use*
chemical_list: D005473:Fluoxetine; D010320:Parvalbumins; D011965:Receptors, Glucocorticoid; D017367:Selective Serotonin Reuptake Inhibitors
keywords: angelman syndrome; anxiety; chronic stress; fluoxetine; parvalbumin