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Inhibition of GALR1 in PFC Alleviates Depressive-Like Behaviors in Postpartum Depression Rat Model by Upregulating CREB-BNDF and 5-HT Levels

Estrogen (E2) withdrawal is a core pathology mechanism for postpartum depression (PPD). Galanin (GAL), an estrogen-inducible neuropeptide has also been reported to be associated with depression. However, it still remains unclear which GAL receptors (GALRs) are involved in PPD pathologic process. In...

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Autores principales: Li, Hui, Wang, Tong, Shi, Cuige, Yang, Yutao, Li, Xiaoxiao, Wu, Yan, Xu, Zhi-Qing David
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Frontiers Media S.A. 2018
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6246688/
https://www.ncbi.nlm.nih.gov/pubmed/30487761
http://dx.doi.org/10.3389/fpsyt.2018.00588
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author Li, Hui
Wang, Tong
Shi, Cuige
Yang, Yutao
Li, Xiaoxiao
Wu, Yan
Xu, Zhi-Qing David
author_facet Li, Hui
Wang, Tong
Shi, Cuige
Yang, Yutao
Li, Xiaoxiao
Wu, Yan
Xu, Zhi-Qing David
author_sort Li, Hui
collection PubMed
description Estrogen (E2) withdrawal is a core pathology mechanism for postpartum depression (PPD). Galanin (GAL), an estrogen-inducible neuropeptide has also been reported to be associated with depression. However, it still remains unclear which GAL receptors (GALRs) are involved in PPD pathologic process. In the present study, we discovered that the expression of GALR1, rather than GALR2/3, was upregulated with a region-specific pattern in the prefrontal cortex (PFC) of E2 withdrawal induced PPD model rats. Meanwhile, c-fos was also upregulated only in PFC in the same animal model. Injection of GALR1-siRNA into the bilateral PFC ameliorated depressive-like behavior of PPD rats, suggesting that the upregulation of GALR1 in PFC is involved in PPD. Moreover, Western Blot and HPLC assays demonstrated that the downregulation of CREB-BDNF signaling and 5-HT levels in the PFC of PPD rats were reversed after GALR1-siRNA injection. These comprehensive results suggest that the knock down of GALR1 in PFC alleviates depressive-like behaviors and reverse downregulation of CREB-BDNF and 5-HT levels in PPD rat model. HIGHLIGHTS  Expression level of GALR1 mRNA was significantly increased in PFC of estrogen withdraw-induced PPD rats. Injecting GALR1-siRNA into PFC alleviated depressive-like behavior and reversed the decrease of 5-HT level and CREB/BDNF signaling in PFC of PPD rats.
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spelling pubmed-62466882018-11-28 Inhibition of GALR1 in PFC Alleviates Depressive-Like Behaviors in Postpartum Depression Rat Model by Upregulating CREB-BNDF and 5-HT Levels Li, Hui Wang, Tong Shi, Cuige Yang, Yutao Li, Xiaoxiao Wu, Yan Xu, Zhi-Qing David Front Psychiatry Psychiatry Estrogen (E2) withdrawal is a core pathology mechanism for postpartum depression (PPD). Galanin (GAL), an estrogen-inducible neuropeptide has also been reported to be associated with depression. However, it still remains unclear which GAL receptors (GALRs) are involved in PPD pathologic process. In the present study, we discovered that the expression of GALR1, rather than GALR2/3, was upregulated with a region-specific pattern in the prefrontal cortex (PFC) of E2 withdrawal induced PPD model rats. Meanwhile, c-fos was also upregulated only in PFC in the same animal model. Injection of GALR1-siRNA into the bilateral PFC ameliorated depressive-like behavior of PPD rats, suggesting that the upregulation of GALR1 in PFC is involved in PPD. Moreover, Western Blot and HPLC assays demonstrated that the downregulation of CREB-BDNF signaling and 5-HT levels in the PFC of PPD rats were reversed after GALR1-siRNA injection. These comprehensive results suggest that the knock down of GALR1 in PFC alleviates depressive-like behaviors and reverse downregulation of CREB-BDNF and 5-HT levels in PPD rat model. HIGHLIGHTS  Expression level of GALR1 mRNA was significantly increased in PFC of estrogen withdraw-induced PPD rats. Injecting GALR1-siRNA into PFC alleviated depressive-like behavior and reversed the decrease of 5-HT level and CREB/BDNF signaling in PFC of PPD rats. Frontiers Media S.A. 2018-11-14 /pmc/articles/PMC6246688/ /pubmed/30487761 http://dx.doi.org/10.3389/fpsyt.2018.00588 Text en Copyright © 2018 Li, Wang, Shi, Yang, Li, Wu and Xu. http://creativecommons.org/licenses/by/4.0/ This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
spellingShingle Psychiatry
Li, Hui
Wang, Tong
Shi, Cuige
Yang, Yutao
Li, Xiaoxiao
Wu, Yan
Xu, Zhi-Qing David
Inhibition of GALR1 in PFC Alleviates Depressive-Like Behaviors in Postpartum Depression Rat Model by Upregulating CREB-BNDF and 5-HT Levels
title Inhibition of GALR1 in PFC Alleviates Depressive-Like Behaviors in Postpartum Depression Rat Model by Upregulating CREB-BNDF and 5-HT Levels
title_full Inhibition of GALR1 in PFC Alleviates Depressive-Like Behaviors in Postpartum Depression Rat Model by Upregulating CREB-BNDF and 5-HT Levels
title_fullStr Inhibition of GALR1 in PFC Alleviates Depressive-Like Behaviors in Postpartum Depression Rat Model by Upregulating CREB-BNDF and 5-HT Levels
title_full_unstemmed Inhibition of GALR1 in PFC Alleviates Depressive-Like Behaviors in Postpartum Depression Rat Model by Upregulating CREB-BNDF and 5-HT Levels
title_short Inhibition of GALR1 in PFC Alleviates Depressive-Like Behaviors in Postpartum Depression Rat Model by Upregulating CREB-BNDF and 5-HT Levels
title_sort inhibition of galr1 in pfc alleviates depressive-like behaviors in postpartum depression rat model by upregulating creb-bndf and 5-ht levels
topic Psychiatry
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6246688/
https://www.ncbi.nlm.nih.gov/pubmed/30487761
http://dx.doi.org/10.3389/fpsyt.2018.00588
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