The Functional Analysis of Intracellular MAPK Pathways in Major Depressive Disorder

Review Article

Austin Med Sci. 2017; 2(1): 1015.

The Functional Analysis of Intracellular MAPK Pathways in Major Depressive Disorder

Joines P, Ludrick B, Golden T and Wu N*

1Department of Biological Sciences, Southeastern Oklahoma State University, Durant, Oklahoma 74701, USA

*Corresponding author: Ning Wu, Department of Biological Sciences, Southeastern Oklahoma State University, Durant, Oklahoma 74701, USA

Received: April 21, 2017; Accepted: May 25, 2017; Published: June 01, 2017

Abstract

The review of scientific evidence strongly links the Mitogen-Activated Protein Kinase (MAPK) pathway with Major Depressive Disorder (MDD). The MAPK pathway has been shown in several marine, porcine and human studies to regulate transcription factors, thus expression of messenger RNA, in multiple neuronal cell types. Specifically, MAPK cascade signaling associations have been demonstrated with cells of the prefrontal cortex and hippocampus, Alzheimer neuronal cells, and raphe nuclei of the brainstem. These findings strongly suggest that continued research of the MAPK pathway will promote novel techniques to treat MDD.

Keywords: Major depressive disorder; MAPK pathway; Signal transduction

Background

Major Depressive Disorder (MDD) is a highly prevalent psychiatric disorder which is becoming an increasingly serious public health concern [1,2]. The symptoms of MDD include (1) feelings of sadness, hopelessness, and overall depressed mood; (2) loss of interest in activities that were previously enjoyable; (3) increased or decreased weight or appetite; (4) change in activity level; (5) difficulty sleeping or excessive sleeping; (6) feeling tired; (7) feelings of guilt; (8) difficulty concentrating; and (9) thoughts of suicide. To be diagnosed with depression a person must exhibit 5 or more symptoms for 2 or more weeks. The primary clinical treatments for MDD include medications and collaborative care which is designed to treat the symptoms of major depressive disorder [3]. Because of the wide range of symptoms of MDD, multiple drug therapies must be utilized.

MDD has been shown to be associated with several different cellular actions (cell growth, apoptosis, differentiation, etc.) and genetic pathways. There have been numerous studies investigating MDD, including the role of the Mitogen-Activated Protein Kinase (MAPK) pathway in MDD and possible treatment modalities that could help alleviate some of the symptoms and presentations of depression. Studies have examined not only the MAPK pathway, but also the genes that play a role in regulation of the MAPK pathways. Topics of research include the role of the immune system [4], epigenetic associated with gene pathways that affect depression [5], effects of genes on astrocytes in people with MDD [6], and drug treatments which could generate neurite growth [7]. Results of these studies have demonstrated that the MAPK pathway plays a key role in the development of MDD.

The MAPK pathway plays a key role in regulating cell proliferation, signal transduction, cell differentiation, and cell death. The MAPK pathways have been grouped into three main families including (1) extracellular signal-regulated (ERK) MAPK, (2) p38 MAPK, and (3) Jun amino (N)-terminal Kinase (JNK) MAPK pathways [8]. After a stimulus moves through different pathways, the MAPK pathway ultimately determines the biological response to the stimulus. When a stressor is introduced to a mammal, the genes in the MAPK pathway play certain roles in inflaming, causing apoptosis, or growing and developing cells. When stress is introduced, the genes in the MAPK pathway that are first affected are inositol 1,4,5-triphosphate (IP3), Protein Kinase C (PKC), and MAPK phosphatase (MKP). Stress results in an up-regulation of these genes. The up-regulation of IP3 and PKC result in the up-regulation of P38 pathway which results in inflammation of cells and apoptosis. The up-regulation of MKP results in the down-regulation of JNK and ERK pathways which results in cell growth, development, and differentiation [2] (Figure 1).

Citation: Joines P, Ludrick B, Golden T and Wu N. The Functional Analysis of Intracellular MAPK Pathways in Major Depressive Disorder. Austin Med Sci. 2017; 2(1): 1015.