Selective serotonin depletion does not regulate hippocampal neurogenesis in the adult rat brain: differential effects of p-chlorophenylalanine and 5,7-dihydroxytryptamine |
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Authors: | Jha Shanker Rajendran Rajeev Davda Jasmine Vaidya Vidita A |
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Affiliation: | Department of Biological Sciences, Tata Institute of Fundamental Research, Mumbai 400005, India. |
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Abstract: | Serotonin is suggested to regulate adult hippocampal neurogenesis, and previous studies with serotonin depletion reported either a decrease or no change in adult hippocampal progenitor proliferation. We have addressed the effects of serotonin depletion on distinct aspects of adult hippocampal neurogenesis, namely the proliferation, survival and terminal differentiation of hippocampal progenitors. We used the serotonin synthesis inhibitor p-chlorophenylalanine (PCPA) or the serotonergic neurotoxin 5,7-dihydroxytryptamine (5,7-DHT) to deplete serotonin levels. 5,7-DHT selectively decreased hippocampal serotonin levels, while PCPA resulted in a significant decline in both serotonin and norepinephrine levels. We observed a robust decline in the proliferation and survival of adult hippocampal progenitors following PCPA treatment. This was supported by a decrease in the number of doublecortin-positive cells in the neurogenic niche in the hippocampus. In striking contrast, 5,7-DHT did not alter the proliferation or survival of adult hippocampal progenitors and did not alter the number of doublecortin-positive cells. The terminal differentiation of adult hippocampal progenitors was not altered by either PCPA or 5,7-DHT treatment. An acute increase in serotonin levels also did not influence adult hippocampal progenitor proliferation. These results suggest that selective serotonin depletion or an acute induction in serotonin levels does not regulate adult hippocampal neurogenesis, whereas treatment with PCPA that induces a decline in both serotonin and norepinephrine levels results in a significant decrease in adult hippocampal neurogenesis. Our results highlight the need for future studies to examine the role of other monoamines in both the effects of stress and antidepressants on adult hippocampal neurogenesis. |
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Keywords: | PCPA, p-chlorophenylalanine PCA, p-chloroamphetamine 5,7-DHT, 5,7-dihydroxytryptamine TCP, tranylcypromine L-Trp, smallcaps" >l-Tryptophan SGZ, subgranular zone GCL, granule cell layer BrdU, 5-bromo-2′-deoxyuridine DG, dentate gyrus SVZ, subventricular zone 5-HT, 5-hydroxytryptamine DβH, dopamine β-hydroxylase DCX, doublecortin NeuN, neuronal nuclei GFAP, glial fibrillary acidic protein SSRI, serotonin selective reuptake inhibitor BDNF, brain-derived neurotrophic factor HPLC, high performance liquid chromatography i.p., intraperitoneal i.c.v., intracerebroventricular SEM, standard error of mean ANOVA, analysis of variance |
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