Expression of Selected Genes Involved in Neurogenesis in the Etiopathogenesis of Depressive Disorders.

Katarzyna Bliźniewska-Kowalska,Monika Talarowska,Piotr Gałecki,Janusz Szemraj

doi:10.3390/jpm11030168

Abstract

(1) Background: The neurogenic theory suggests that impaired neurogenesis within the dentate gyrus of the hippocampus is one of the factors causing depression. Immunology also has an impact on neurotrophic factors. The aim of the study was to assess the importance of selected genes involved in the process of neurogenesis i.e., nerve growth factor (NGF), brain-derived neurotrophic factor (BDNF), glial-derived neurotrophic factor (GDNF) and neuron-restrictive silencer factor (REST gene) in the etiopathogenesis of depressive disorders. (2) Methods: A total of 189 subjects took part in the study (95 depressed patients, 94 healthy controls). Sociodemographic data were collected. The severity of depressive symptoms was assessed using the Hamilton Depression Rating Scale (HDRS). RT-PCR was used to assess gene expression at the mRNA levels, while Enzyme-Linked Immunosorbent Assay (ELISA) was used to assess gene expression at the protein level. (3) Results: Expression of NGF, BDNF, REST genes is lower in depressed patients than in the control group, whereas the expression of GDNF gene is higher in patients with depressive disorders than in the group of healthy volunteers. (4) Conclusions: The expression of selected genes might serve as a biomarker of depression.

Highlights

Expression of nerve growth factor (NGF), brain-derived neurotrophic factor (BDNF), and RE1-Silencing Transcription factor (REST) genes at both protein and mRNA levels was lower in patients with depressive disorders than in the control group
A meta-analysis performed by Chen et al, which included seven studies comparing peripheral NGF in depressed patients and healthy subjects, to this study, found that NGF levels were significantly lower in depressed patients than in healthy subjects and that this had an inverse correlation with mean age and disease severity
Expression of the NGF, BDNF, and REST genes at both protein and mRNA levels is lower in patients with depressive disorders than in the control group

Summary

Introduction

The neurogenic theory proposes that impaired adult neurogenesis within the dentate gyrus of the hippocampus is one of the factors causing depression and the restoration of normal neurogenesis leads to recovery [1]. The hippocampus as part of the limbic system is considered to be the so-called “emotional brain” and the area where the process of adult neurogenesis (AHN) takes place It is a frequently studied structure in the investigation of depressive disorders. Glucocorticosteroids affect the process of neurogenesis, both directly and indirectly, by activating pro-inflammatory genes and by reducing the expression of main regulators of neurogenesis, i.e., brain-derived neurotrophic factor (BDNF) [4,5] Another evidence that supports this theory is a fact that depressed patients have, on average, a smaller volume of the hippocampus [6]. A decrease in synaptic density within the hippocampus correlates with the severity of depressive symptoms [7]

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