Changes of dopamine content and cell proliferation by dexamethsone via pituitary adenylate cyclase-activating polypeptide in PC12 cell

doi:10.1016/j.neulet.2007.08.037

Neuroscience Letters

Volume 426, Issue 1, 9 October 2007, Pages 45-48

https://doi.org/10.1016/j.neulet.2007.08.037 Get rights and content

Abstract

Pituitary adenylate cyclase-activating polypeptide (PACAP) is an endogenous neuropeptide observed in adrenal gland and sympathetic ganglia to regulate catecholamine synthesis and release. Both PACAP and glucocorticoid showed the activity to elevate catecholamine level through the stimulation of biosynthesis. However, the relationship of glucocorticoid and PACAP for this action is still unclear. Thus, alterations of gene expression, dopamine (DA) content, and cell proliferation in rat pheochromocytoma PC12 cells are employed as indicators to clarify this relationship in the present study. From the analysis of RT-PCR, the mRNA level of PACAP was observed to be raised by dexamethasone (DEX) and this action was blocked in cells treated with RU486 (mifepristone), a glucocorticoid receptor (GR) antagonist, or actinomycin D, a transcriptional inhibitor. An increase of DA content by HPLC analysis and/or cell proliferation identified by MTT assay by DEX was also observed which could be inhibited by PACAP (6–38) at concentration sufficient to block PACAP type 1 (PAC1) receptor. These results suggest that PACAP is involved in DEX-induced DA biosynthesis and cell proliferation in PC12 cells.

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Acknowledgments

We appreciate Miss F.Y. Jou for research assistance. The present study was supported in part by a grant from China Medical University (CMU92-CI-02).

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GR coupled with ɑ1-adrenoceptor has an impact on β-adrenoceptor-cAMP system (Kasssel and Herrlich, 2002), and can activate NA system by activating NE nerve cell group in brainstem (Chen et al., 2012). GR can also regulate the transcription The activated GR bounded to glucocorticoid response element (GRE)not only influences gene expression but also disturbs other transcriptional factors, such as NF-kB, AP-1, CREB, etc., which in turn influence the combination of cAMP and PKA regulatory subtypes, consequently, affecting the production and survival of DA neurons and regulating the activity and secretion of DA, that will adjust the function of DA system and help to maintain the normal function of the body (Yang et al., 2007). In this study, our result suggests that exogenous GR agonist DEX and GR inhibitor RU486 can affect dopaminergic neurotransmitters in the brain.
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Intracranial self-stimulation (ICSS) within the medial forebrain bundle of the lateral hypothalamus (LH) facilitates consolidation of implicit and explicit memories for a variety of learning paradigms in rats. However, the neural and molecular mechanisms involved in memory facilitation by ICSS are not known. Here, we investigated the influence of ICSS treatment on hippocampal gene expression in order to identify potential signaling pathways and cellular processes involved in ICSS-mediated cognitive improvements. Immunohistochemistry studies demonstrated that ICSS caused a rapid induction of c-Fos expression in hippocampal cornu ammonis (CA) 3 and dentatus gyrus areas. Moreover, using microarray or quantitative real-time polymerase chain reaction (PCR) analysis, we showed that ICSS modulates the expression of 62 hippocampal genes shortly after training. Most of the proteins encoded by these genes, such as calmodulin-dependent-phosphodiesterase 1 A (Pde1a), are part of signal transduction machineries or are related to anti-apoptosis, as heat shock 70 kDa protein 1A (Hspa1a). Importantly, 10 of the regulated genes have been previously related with learning and memory or neural plasticity, including the cocaine and amphetamine-regulated transcript (Cart), adenylate cyclase activating polypeptide 1 (Adcyap1), serum/glucocorticoid regulated kinase (Sgk), Ret proto-oncogene (Ret), and Fos. The fact that the Fos gene was differentially expressed in our microarray experiments validated our findings from our immunohistochemical studies mentioned above. In addition, using quantitative real-time PCR, we confirmed the observed expression changes for several of the genes identified by our microarray analyses. Our results suggest that ICSS may facilitate learning and memory by regulation of multiple signaling pathways in the hippocampus that may promote neuroplasticity.
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Changes of dopamine content and cell proliferation by dexamethsone via pituitary adenylate cyclase-activating polypeptide in PC12 cell

Abstract

Section snippets

Acknowledgments

Biochem. Biophys. Res. Commun.

Exp. Neurol.

J. Biol. Chem.

Regul. Pept.

J. Biol. Chem.

Regul. Pept.

Prog. Neurobiol.

Eur. J. Pharmacol.

Molecular control of cell fate in the neural crest: the sympathoadrenal lineage

Annu. Rev. Neurosci.

Perspectives on pituitary adenylate cyclase activating polypeptide (PACAP) in the neuroendocrine, endocrine, and nervous systems

Jpn. J. Physiol.

Pituitary adenylate cyclase activating polypeptide (PACAP): discovery and current status of research

Regul. Pept.