The effects of chronic desipramine treatment on neurotrophin-3 in the brain of mice with selective depletion of CREB and CREM in noradrenergic neurons.

Autor: Rafa-Zabłocka K; Dept. Brain Biochemistry, Maj Institute of Pharmacology, Polish Academy of Sciences, 31-343, Krakow, Smetna 12, Poland., Nalepa I; Dept. Brain Biochemistry, Maj Institute of Pharmacology, Polish Academy of Sciences, 31-343, Krakow, Smetna 12, Poland., Kreiner G; Dept. Brain Biochemistry, Maj Institute of Pharmacology, Polish Academy of Sciences, 31-343, Krakow, Smetna 12, Poland. Electronic address: kreiner@if-pan.krakow.pl.
Jazyk: angličtina
Zdroj: Neuroscience [Neuroscience] 2024 Dec 06; Vol. 562, pp. 190-197. Date of Electronic Publication: 2024 Oct 22.
DOI: 10.1016/j.neuroscience.2024.10.020
Abstrakt: The disturbances in neurotrophic support are thought to be one of the main causes of depression, which depend not only on the neurotrophins themselves but also on the molecules regulating their synthesis and effector functions. One such molecule is cAMP responsive element binding protein (CREB), which role in depression and antidepressant drugs mechanism of action has been extensively studied. However, CREB's effects vary depending on brain structure, necessitating specific transgenic models for studying its function. Moreover, deletion of CREB enhances cAMP response element modulator (CREM) expression, suspected to compensate for CREB in its absence. Previously, mice lacking CREB in noradrenergic neurons and CREM (Creb1 DbhCre Crem-/-) showed to be insensitive to acute desipramine, whereas mice lacking only CREB (Creb1 DbhCre ) showed similar effects as wild type animals (w/t). As neurotrophic changes require chronic antidepressant treatment, in current study mice (w/t, Creb1 DbhCre and Creb1 DbhCre Crem-/-; both males and females) were given desipramine for 21 days, to assess the effects of the drug on CREB, neurotrophins and their receptors in the hippocampus and prefrontal cortex. Interestingly, desipramine had no effect on CREB in neither of studied groups. However, both male and female mice lacking CREB and CREM displayed alterations in neurotrophin-3 (NTF3) expression or protein levels, modulated by desipramine. These findings suggest NTF3 is connected with inhibited response to acute and probably chronic desipramine administration in Creb1 DbhCre Crem-/- mice, although in w/t chronic desipramine had no effect on NTF3. Nevertheless, our findings give insight into the role of non-BDNF neurotrophins in the mechanism of antidepressant drugs.
Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper.
(Copyright © 2024 International Brain Research Organization (IBRO). Published by Elsevier Inc. All rights reserved.)
Databáze: MEDLINE
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