Back to Search
Start Over
The effects of chronic desipramine treatment on neurotrophin-3 in the brain of mice with selective depletion of CREB and CREM in noradrenergic neurons.
- Source :
-
Neuroscience . Dec2024, Vol. 562, p190-197. 8p. - Publication Year :
- 2024
-
Abstract
- • Desipramine treatment does not affect pCREB and CREB protein expression in mice; • Desipramine treatment modulates mRNA of Bdnf/Ntf3; • Desipramine treatment affects NTF3 in males lacking CREB/CREM in NA neurons. 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 (Creb1DbhCreCrem-/-) showed to be insensitive to acute desipramine, whereas mice lacking only CREB (Creb1DbhCre) showed similar effects as wild type animals (w/t). As neurotrophic changes require chronic antidepressant treatment, in current study mice (w/t, Creb1DbhCre and Creb1DbhCreCrem-/-; 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 Creb1DbhCreCrem–/– 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. [ABSTRACT FROM AUTHOR]
Details
- Language :
- English
- ISSN :
- 03064522
- Volume :
- 562
- Database :
- Academic Search Index
- Journal :
- Neuroscience
- Publication Type :
- Academic Journal
- Accession number :
- 180954705
- Full Text :
- https://doi.org/10.1016/j.neuroscience.2024.10.020