Morphometric post-mortem studies in bipolar disorder: possible association with oxidative stress and apoptosis

Abstract

Despite extensive research in the last decades, the pathophysiology of bipolar disorder (BD) remains unclear. Access to post-mortem brain tissue of subjects who had BD offers an opportunity to investigate neurobiology and this approach has led to some progress, particularly, due to the availability of more sophisticated molecular and cellular biological methodologies and well characterized brain collections over the past decade. Here we review the findings of morphometric post-mortem studies in BD and interpret them in the context of a potential physiopathological mechanism involving oxidative stress and apoptosis. A review of the literature was conducted to identify post-mortem studies that investigated cellular changes such as number, density and size of neurons and glia, in brains of subjects with BD. We found decreased density of neurons and glia and decreased size of neurons in frontal and subcortical areas of the brain. Based on recent studies that found evidence of increased apoptosis and oxidative stress in BD, we hypothesize that the cell abnormalities described are due to an increase in the apoptotic process that can be triggered, through its intrinsic pathway, by the existence of an exacerbated production of reactive oxygen species and oxidative damage in the disease.

Role of Protein Kinase C in Bipolar Disorder: A Review of the Current Literature

“…Glutamatergic excitotoxicity is another putative mechanisms proposed in BD pathophysiology [123]. A meta-analysis revealed that glutamate levels were increased in several brain regions of patients with BD [124].…”

The Effects of Different Types of Chronic Stress on Morphometric Changes and Apoptosis of Betz Cells in the Internal Pyramidal Layer of the Cerebral Cortex of Rats

“…Psychosocial stress led to damage of nerve cells in the rat, with the stress affecting interleukin and lipid peroxidation and inducing apoptosis of hippocampal cells (32). In a study of the number, size, and density of cells and the incidence of apoptosis in neurons and glial cells in the brains of people with bipolar disorder after death, oxidative stress increased the expression of apoptosis and reduced the size and number of cells (33). The results of the present study showed that chronic sequential stress had negative effects on rat cerebral cortex by reducing the size and number of Betz cells and increasing the incidence of apoptosis.…”

The Impact of Oxidative Stress on Dopaminergic Neurotransmission

“…Due to inherent oxidative conditions prevalent in the striatum, the investigation of redox effects on dopaminergic parameters should be of paramount importance; the wealth of data in this domain has been devised to mimic neurodegenerative disorders, chiefl y Parkinsons's and Huntington's diseases, and does not extrapolate well to psychiatric disorders. In parallel with their ongoing demonstration in post-mortem (Gigante et al 2010 ;Wang et al 2009 ) and clinical (Do et al 2000 ) contexts, a careful investigation of oxidative phenomena, clinically relevant in intensity and duration, in well-chosen animal models should continue to provide important contributions to our understanding of the dopaminergic aspects of schizophrenia pathophysiology. …”