The BDNF-TrkB Pathway Acts Through Nucleus Accumbens D2 Expressing Neurons to Mediate Stress Susceptible Outcomes.

Autor:	Pagliusi M Jr; Department of Anatomy and Neurobiology, University of Maryland School of Medicine, Baltimore, MD, United States.; Department of Structural and Functional Biology, University of Campinas, Campinas, Brazil., Franco D; Department of Anatomy and Neurobiology, University of Maryland School of Medicine, Baltimore, MD, United States., Cole S; Department of Anatomy and Neurobiology, University of Maryland School of Medicine, Baltimore, MD, United States., Morais-Silva G; Department of Anatomy and Neurobiology, University of Maryland School of Medicine, Baltimore, MD, United States.; School of Pharmaceutical Sciences, São Paulo State University, Araraquara, Brazil., Chandra R; Department of Anatomy and Neurobiology, University of Maryland School of Medicine, Baltimore, MD, United States., Fox ME; Department of Anatomy and Neurobiology, University of Maryland School of Medicine, Baltimore, MD, United States., Iñiguez SD; Department of Psychology, University of Texas at El Paso, El Paso, TX, United States., Sartori CR; Department of Structural and Functional Biology, University of Campinas, Campinas, Brazil., Lobo MK; Department of Anatomy and Neurobiology, University of Maryland School of Medicine, Baltimore, MD, United States.
Jazyk:	angličtina
Zdroj:	Frontiers in psychiatry [Front Psychiatry] 2022 Jun 02; Vol. 13, pp. 854494. Date of Electronic Publication: 2022 Jun 02 (Print Publication: 2022).
DOI:	10.3389/fpsyt.2022.854494
Abstrakt:	Brain-derived neurotrophic factor (BDNF) has a critical role in stress response including neuropsychiatric disorders that are precipitated by stress, such as major depressive disorder (MDD). BDNF acts through its full-length BDNF receptor tyrosine kinase B (TrkB) to trigger a pro-plasticity effect. In contrast, the truncated isoform of the BDNF receptor (TrkB.t1) triggers an anti-plasticity effect. In stress outcomes, BDNF acting in the hippocampus has a stress resilience effect, and, inversely, in the nucleus accumbens (NAc), BDNF acts as a stress susceptible molecule. It is unknown if BDNF-TrkB acts on a specific NAc projection neuron, i.e., medium spiny neuron (MSN or spiny projection neuron), a subtype in stress outcomes. To determine this, we performed chronic social or vicarious witness defeat stress (CSDS or CWDS) in mice expressing TrkB.t1 in dopamine receptor 1 or 2 containing MSNs (D1- or D2-MSNs). Our results showed that TrkB.t1 overexpression in NAc D2-MSNs prevented the CSDS-induced social avoidance or other stress susceptible behaviors in male and female mice. We further showed that this overexpression in D2-MSNs blocked stress susceptible behavior induced by intra-NAc BDNF infusion. In contrast, our results demonstrate that overexpression of TrkB.t1 on NAc D1-MSNs facilitates the SDS susceptible behaviors. Our study provides enhanced details into the NAc cell subtype role of BDNF-TrkB signaling in stress outcomes. Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest. (Copyright © 2022 Pagliusi, Franco, Cole, Morais-Silva, Chandra, Fox, Iñiguez, Sartori and Lobo.)
Databáze:	MEDLINE
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