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Substance P, NPY, CCK and their receptors in five brain regions in major depressive disorder with transcriptomic analysis of locus coeruleus neurons

Bibliographic Details
Title: Substance P, NPY, CCK and their receptors in five brain regions in major depressive disorder with transcriptomic analysis of locus coeruleus neurons
Authors: Barde, Swapnali, Author, Aguila, Julio, Author, Zhong, Wen, Author, Solarz, Anna, Author, Mei, Irene, Author, Prud'homme, Josee, Author, Palkovits, Miklos, Author, Turecki, Gustavo, Author, Mulder, Jan, Author, Uhlen, Mathias, Author, Nagy, Corina, Author, Mechawar, Naguib, Author, Hedlund, Eva, Author, Hokfelt, Tomas, Author
Contributors: Barde, Swapnali, Author, Aguila, Julio, Author, Zhong, Wen, Author, Solarz, Anna, Author, Mei, Irene, Author, Prud'homme, Josee, Author, Palkovits, Miklos, Author, Turecki, Gustavo, Author, Mulder, Jan, Author, Uhlen, Mathias, Author, Nagy, Corina, Author, Mechawar, Naguib, Author, Hedlund, Eva, Author, Hokfelt, Tomas, Author
Source: European Neuropsychopharmacology. 78:54-63
Subject Terms: Human brain, Laser capture microdissection, Neuropeptides, qPCR, VGLUT
Description: Major depressive disorder (MDD) is a serious disease and a burden to patients, families and society. Rodent experiments and human studies suggest that several neuropeptide systems are involved in mood regulation. The aim of this study is two-fold: (i) to monitor, with qPCR, transcript levels of the substance P/tachykinin (TAC), NPY and CCK systems in bulk samples from control and suicide subjects, targeting five postmortem brain regions including locus coeruleus (LC); and (ii) to analyse expression of neuropeptide family transcripts in LC neurons of 'normal' postmortem brains by using laser capture microdissection with Smart-Seq2 RNA sequencing. qPCR revealed distinct regional expression patterns in male and female controls with higher levels for the TAC system in the dorsal raphe nucleus and LC, versus higher transcripts levels of the NPY and CCK systems in prefrontal cortex. In suicide patients, TAC, TAC receptors and a few NPY family transcript levels were increased mainly in prefrontal cortex and LC. The second study on 'normal' noradrenergic LC neurons revealed expression of transcripts for GAL, NPY, TAC1, CCK, and TACR1 and many other peptides (e.g. Cerebellin4 and CARTPT) and receptors (e.g. Adcyap1R1 and GPR173). These data and our previous results on suicide brains indicates that the tachykinin and galanin systems may be valid targets for developing antidepressant medicines. Moreover, the perturbation of neuropeptide systems in MDD patients, and the detection of further neuropeptide and receptor transcripts in LC, shed new light on signalling in noradrenergic LC neurons and on mechanisms possibly associated with mood disorders.
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Access URL: https://urn.kb.se/resolve?urn=urn:nbn:se:kth:diva-340983
https://doi.org/10.1016/j.euroneuro.2023.09.004
Database: SwePub
Description
ISSN:0924977X
18737862
DOI:10.1016/j.euroneuro.2023.09.004