Early life stress alters adult serotonin 2C receptor pre-mRNA editing and expression of the alpha subunit of the heterotrimeric G-protein G q.
Infant maternal separation, a paradigm of early life stress in rodents, elicits long-lasting changes in gene expression that persist into adulthood. In BALB/c mice, an inbred strain with spontaneously elevated anxiety and stress reactivity, infant maternal separation led to increased depression-like behavioral responses to adult stress and robustly increased editing of serotonin 2C receptor pre-mRNA. Chronic fluoxetine treatment of adult BALB/c mice exposed to early life stress affected neither their behavioral responses to stress nor their basal 5-HT2C pre-mRNA editing phenotype. However, when fluoxetine was administered during adolescence, depression-like behavioral responses to stress were significantly diminished in these mice, and their basal and stress-induced 5-HT2C pre-mRNA editing phenotypes were significantly lower. Moreover, when BALB/c mice exposed to early life stress were raised in an enriched postweaning environment, their depression-like behavioral responses to adult stress were also significantly diminished. However, their 5-HT2C pre-mRNA editing phenotype remained unaltered. Hence, the similar behavioral effects of enrichment and fluoxetine treatment during adolescence were not accompanied by similar changes in 5-HT2C pre-mRNA editing. Enriched and nonenriched BALB/c mice exposed to early life stress also exhibited significantly increased expression of mRNA and protein encoding the G alpha q subunit of G-protein that couples to 5-HT2A/2C receptors. In contrast, G alpha q expression levels were significantly lower in fluoxetine-treated mice. These findings suggest that compensatory changes in G alpha q expression occur in mice with persistently altered 5-HT2C pre-mRNA editing and provide an explanation for the dissociation between 5-HT2C receptor editing phenotypes and behavioral stress responses.
Bhansali
Punita
P
Department of Psychiatry, Columbia University, New York, New York 10032, USA.
Dunning
Jane
J
Singer
Sarah E
SE
David
Leora
L
Schmauss
Claudia
C
D000367:Age Factors; D000818:Animals; D001010:Anxiety, Separation / Q000150:complications / Q000235:genetics* / Q000523:psychology; D001835:Body Weight; D003866:Depressive Disorder / Q000188:drug therapy / Q000209:etiology / Q000235:genetics* / Q000503:physiopathology / Q000523:psychology; D004644:Emotions; D004777:Environment; D005260:Female; D005473:Fluoxetine / Q000494:pharmacology / Q000627:therapeutic use; D043802:GTP-Binding Protein alpha Subunits, Gq-G11 / Q000096:biosynthesis / Q000235:genetics*; D020022:Genetic Predisposition to Disease; D006380:Helplessness, Learned; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C / Q000235:genetics / Q000502:physiology* / Q000523:psychology; D008810:Mice, Inbred C57BL; D019579:Neocortex / Q000378:metabolism; D020033:Protein Isoforms / Q000096:biosynthesis / Q000235:genetics / Q000502:physiology; D017393:RNA Editing; D012322:RNA Precursors / Q000235:genetics*; D011897:Random Allocation; D044405:Receptor, Serotonin, 5-HT2C / Q000096:biosynthesis / Q000235:genetics* / Q000502:physiology; D012701:Serotonin / Q000502:physiology*; D017367:Selective Serotonin Reuptake Inhibitors / Q000494:pharmacology / Q000627:therapeutic use; D013045:Species Specificity; D013550:Swimming
D005473:Fluoxetine; D043802:GTP-Binding Protein alpha Subunits, Gq-G11; D020033:Protein Isoforms; D012322:RNA Precursors; D044405:Receptor, Serotonin, 5-HT2C; D012701:Serotonin; D017367:Selective Serotonin Reuptake Inhibitors