Reversal of reduced parvalbumin neurons in hippocampus and amygdala of Angelman syndrome model mice by chronic treatment of fluoxetine. (25th April 2014)

• Record Type: Journal Article
• Authors: Godavarthi, Swetha K.; Sharma, Ankit; Jana, Nihar Ranjan
• Is Part Of: Journal of neurochemistry. Volume 130:Number 3(2014:Aug.)
• Page Start: 444
• Page End: 454
• Publication Date: 2014-04-25
• Subjects: Neurochemistry -- Periodicals; 616.8042
• DOI: 10.1111/jnc.12726
• Languages: English
• ISSNs: 0022-3042

Abstract

<abstract abstract-type="main" id="jnc12726-abs-0001"> <title>Abstract</title> <p>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 <italic>UBE3A</italic>. <italic>Ube3a</italic> 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. <boxed-text content-type="graphic" id="jnc12726-blkfxd-0001" position="anchor" orientation="portrait"><graphic position="anchor" mimetype="image" xlink:href="ark:/27927/pght8nxs2q" orientation="portrait" xlink:type="simple" xmlns:xlink="http://www.w3.org/1999/xlink" /></boxed-text></p> <p>This report showed that the reduction of parvalbumin (PV) in hippocampus and basolateral amygdala (BLA) along with altered glucocorticoid receptor (GR) signalling from early post‐natal days results in stress and anxiety in AS mice. Fluoxetine treatment rescues GR signalling and PV expression and partially restores anxiety‐like behaviour. These findings suggest critical evaluation of anxiety and therapeutic implication of fluoxetine in AS patients.</p> </abstract>