» Articles » PMID: 24345476

Lack of BDNF Expression Through Promoter IV Disturbs Expression of Monoamine Genes in the Frontal Cortex and Hippocampus

Overview
Journal Neuroscience
Specialty Neurology
Date 2013 Dec 19
PMID 24345476
Citations 26
Authors
Affiliations
Soon will be listed here.
Abstract

Brain-derived neurotrophic factor (BDNF) is implicated in the pathophysiology of psychiatric conditions including major depression and schizophrenia. Mice lacking activity-driven BDNF expression through promoter IV (knock-in promoter IV: KIV) exhibit depression-like behavior, inflexible learning, and impaired response inhibition. Monoamine systems (serotonin, dopamine, and noradrenaline) are suggested to be involved in depression and schizophrenia since many of the current antidepressants and antipsychotics increase the brain levels of monoamines and/or act on monoamine receptors. To elucidate the impact of activity-driven BDNF on the monoamine systems, we examined mRNA levels for 30 monoamine-related genes, including receptors, transporters, and synthesizing enzymes, in KIV and control wild-type mice by using quantitative reverse-transcription polymerase chain reaction (qRT-PCR). mRNA levels were measured in the frontal cortex and hippocampus, which are regions related to depression and schizophrenia and where promoter IV is active. The frontal cortex of KIV mice showed reduced levels of mRNA expression for serotonin receptors 1b, 2a, and 5b (5HTR1b, 5HTR2a, 5HTR5b), dopamine D2 receptors (DRD2), and adrenergic receptors alpha 1a and 1d (AdRα1a and AdRα1b), but increased levels for serotonin synthesizing enzyme, tryptophan hydroxylase (TPH), and dopamine D4 receptor (DRD4) when compared to control wild-type mice. The hippocampus of KIV mice showed decreased levels of 5HTR5b. Our results provide causal evidence that lack of promoter IV-driven BDNF disturbs expression of monoaminergic genes in the frontal cortex and hippocampus. These disturbed expression changes in the monoamine systems may mediate the depression- and schizophrenia-like behavior of KIV mice. Our results also suggest that antidepressant and antipsychotic treatments may actually interfere with and normalize the disturbed monoamine systems caused by reduced activity-dependent BDNF, while the treatment responses to these drugs may differ in the subject with reduced BDNF levels caused by stress and lack of neuronal activity.

Citing Articles

Epigenetic mechanisms of rapid-acting antidepressants.

Inserra A, Campanale A, Rezai T, Romualdi P, Rubino T Transl Psychiatry. 2024; 14(1):359.

PMID: 39231927 PMC: 11375021. DOI: 10.1038/s41398-024-03055-y.


Ketamine Produces Antidepressant Effects by Inhibiting Histone Deacetylases and Upregulating Hippocampal Brain-Derived Neurotrophic Factor Levels in a Diisopropyl Fluorophosphate-Based Rat Model of Gulf War Illness.

Ribeiro-Davis A, Al Saeedy D, Jahr F, Hawkins E, McClay J, Deshpande L J Pharmacol Exp Ther. 2023; 388(2):647-654.

PMID: 37863487 PMC: 10801753. DOI: 10.1124/jpet.123.001824.


Diverse Functions of Multiple Transcripts Driven by Distinct Promoters.

You H, Lu B Biomolecules. 2023; 13(4).

PMID: 37189402 PMC: 10135494. DOI: 10.3390/biom13040655.


Flavonols in Action: Targeting Oxidative Stress and Neuroinflammation in Major Depressive Disorder.

Jazvinscak Jembrek M, Orsolic N, Karlovic D, Peitl V Int J Mol Sci. 2023; 24(8).

PMID: 37108052 PMC: 10138550. DOI: 10.3390/ijms24086888.


A novel intergenic enhancer that regulates expression in developing cortical neurons.

Brookes E, Martinez De La Cruz B, Boulasiki P, Au H, Varsally W, Barrington C iScience. 2022; 26(1):105695.

PMID: 36582820 PMC: 9792897. DOI: 10.1016/j.isci.2022.105695.