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The role of BDNF, CREB, DAT, GFAP and Arc in manic- and OCD-like behavioral phenotypes in both sexes of rats exposed to REM sleep deprivation
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DOI：10.1186/s12993-026-00359-5.png)
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Abstract
En 中文
Rapid-eye movement sleep deprivation (REM SD) has controversial effects on behavioral functions and cognitive abilities. Recent evidence has shown that REM SD in rats may lead to manic- and obsessive-compulsive disorder (OCD)-like behaviors. The present study aimed to assess the effect of REM SD in both sexes of rats on locomotor activity, anxiety-like behavior, stereotyped behaviors, and OCD-like behavior. The possible role of brain-derived neurotrophic factor (BDNF), cAMP response element-binding (CREB), dopamine transporter (DAT), glia fibrillary acidic protein (GFAP), and activity-regulated cytoskeleton-associated protein (Arc) was also assessed using real-time PCR. REM SD was done for 14 days (6 h/d). Locomotor activity, anxiety-like behavior, grooming, and sniffing were measured using the open field test, and the marble burying test measured repetitive/compulsive-like responses. The results showed REM SD in both sexes led to hyperlocomotion, decreased anxiety, and increased OCD-like and stereotyped behaviors, with more effects in females except anxiety-like behavior. Also, the expression level of BDNF, CREB, DAT, and Arc was decreased and GFAP was increased in the hippocampus of both sexes of REM SD rats, with more effects in females except CREB. In conclusion, and for the first time, the present study showed the possible role of Arc, DAT, and GFAP in the induction of OCD- and manic-like behaviors and stereotyped behaviors in both sexes of rats. We also observed reduced BDNF and CREB expression in REM SD animals, suggesting a potential association between these molecular alterations and the behavioral changes induced by REM SD. Interventions targeting these molecular pathways could offer promising therapeutic strategies for REM SD-induced mood disorders.
Keywords:
Locomotor activity
Obsessive-compulsive-like behavior
Manic-like behavior
Anxiety-like behavior
Dopaminergic signaling
Astrocyte activation
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