Abstract
Glutamatergic dysregulation is known to contribute to altered emotional regulation. Astrocytic glutamate transporter 1 (GLT1) is responsible for the majority of glutamate clearance from synapse. However, the role of astrocytic GLT1 in affective processes such as anxiety- and depression-like behavior is not fully understood. Here, we found that astrocytic GLT1 deficient mice entered more frequently, and spent more time in the open arms of elevated plus maze without difference in overall distance traveled in the open field, nor were there any metabolic changes observed in the metabolic chamber compared to wildtype mice. Moreover, mice lacking astrocytic GLT1 exhibited less immobile time and moved greater area in the tail suspension test. Similarly, in the forced swim test, they showed less immobile time and moved greater area. In addition, we found that astrocytic GLT1 deficiency reduced freezing responses in the fear contextual and cued tests. Taken together, our findings suggest that astrocytic GLT1 deficiency decreases anxiety and depression-like behaviors.
Highlights
Major depressive disorder (MDD) is a mental health disorder that displays a combination of symptoms, including reduced motivation and activities, helplessness, loss of appetite or interest, and sleep disturbance (Kessler et al, 2003; Cui et al, 2014), causing significant impairment in daily life
This study demonstrates that GFAP-positive astrocyte-specific deletion of glutamate transporter 1 (GLT1) reduced anxiety- and depression-like behaviors using a comprehensive array of behavioral tests including Elevated plus maze (EPM), TST and forced swim tests (FSTs)
The freezing response in fear conditioning test was reduced in GFAP-positive astrocytic GLT1 deficient mice. These results suggest that GFAP-positive astrocytic GLT1 is associated with emotional regulation such as anxiety, depression, and fear expression
Summary
Major depressive disorder (MDD) is a mental health disorder that displays a combination of symptoms, including reduced motivation and activities, helplessness, loss of appetite or interest, and sleep disturbance (Kessler et al, 2003; Cui et al, 2014), causing significant impairment in daily life. Generalized anxiety disorder (GAD) is one of the most common psychiatric disorders and co-occurring illness with MDD (Sunderland et al, 2010). This co-occurrence may indicate a similar etiology and pathophysiological abnormalities in MDD and GAD (Mineka et al, 1998). High rates of comorbidity (Zbozinek et al, 2012), and similar brain abnormalities are possibly attributed to both anhedonia and anxiogenesis (John et al, 2015).
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