Expression of substance P, NPY and their Receptors Is Altered in Major Depression

Barde, S.; Aguila, J.; Zhong, W.; Solarz, A.; Mei, I.; Prud'homme, J.; Palkovits, M.; Turecki, G.; Mulder, J.; Uhlen, M.; Nagy, C.; Mechawar, N.; Hedlund, E.; Hokfelt, T.

doi:10.1101/2022.12.14.516867

bioRxiv · 10.1101/2022.12.14.516867

Expression of substance P, NPY and their Receptors Is Altered in Major Depression

Barde, S.·Aguila, J.·Zhong, W.·Solarz, A.·Mei, I.·Prud'homme, J.·Palkovits, M.·Turecki, G.·Mulder, J.·Uhlen, M.·Nagy, C.·Mechawar, N.·Hedlund, E.·Hokfelt, T.

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Abstract

BACKGROUNDMajor 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, including substance P(SP)/tachykinin, neuropeptide Y(NPY) and their G protein-coupled receptors are involved in mood regulation. METHODSWe assessed the transcript levels (qPCR) of SP/tachykinin and NPY systems in five regions from postmortem brains of male and female depressed subjects who committed suicide (DSS) and controls: dorsolateral prefrontal cortex (DLPFC), anterior cingulate cortex (ACC), the dorsal raphe nucleus (DRN), locus coeruleus (LC) and medullary raphe nuclei (MRN). We also analysed human LC neurons isolated using LCM with Smart-seq2 RNA sequencing. RESULTSTranscripts for all nine members were detected in male and female controls with marked regional variations of the raw CT values and with the highest levels for several tachykinin and tachykinin receptor transcripts in the DRN and for NPY and NPYR transcripts in the PFC regions. Significant sex differences for controls were recorded only in the DRN (NPYR2 >in females) and LC (TAC3 and NPY >in females). Elevated expression in DSS was recorded in (i) DLPFC for SP, TAC and TAC3 in females, SP in males, and NPYR1 in both sexes; and (ii) LC for all tachykinin family transcripts in females, SP, TACR1 and TACR3 in males, NPY in both sexes, and NPYR1 in males. CONCLUSIONSThe selective perturbation of neuropeptide systems in MDD patients may assist in the search for novel treatment strategies for subjects afflicted by this grave disorder.

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Barde, S., Aguila, J., Zhong, W., Solarz, A., Mei, I., Prud'homme, J., Palkovits, M., Turecki, G., Mulder, J., Uhlen, M., Nagy, C., Mechawar, N., Hedlund, E., Hokfelt, T.. 2022-12-15. Expression of substance P, NPY and their Receptors Is Altered in Major Depression. https://doi.org/10.1101/2022.12.14.516867

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