Concepts of Neuroinflammation and Their Relationship With Impaired Mitochondrial Functions in Bipolar Disorder

Abstract

Bipolar disorder (BD) is a chronic psychiatric disease, characterized by frequent behavioral episodes of depression and mania, and neurologically by dysregulated neurotransmission, neuroplasticity, growth factor signaling, and metabolism, as well as oxidative stress, and neuronal apoptosis, contributing to chronic neuroinflammation. These abnormalities result from complex interactions between multiple susceptibility genes and environmental factors such as stress. The neurocellular abnormalities of BD can result in gross morphological changes, such as reduced prefrontal and hippocampal volume, and circuit reorganization resulting in cognitive and emotional deficits. The term “neuroprogression” is used to denote the progressive changes from early to late stages, as BD severity and loss of treatment response correlate with the number of past episodes. In addition to circuit and cellular abnormalities, BD is associated with dysfunctional mitochondria, leading to severe metabolic disruption in high energy-demanding neurons and glia. Indeed, mitochondrial dysfunction involving electron transport chain (ETC) disruption is considered the primary cause of chronic oxidative stress in BD. The ensuing damage to membrane lipids, proteins, and DNA further perpetuates oxidative stress and neuroinflammation, creating a perpetuating pathogenic cycle. A deeper understanding of BD pathophysiology and identification of associated biomarkers of neuroinflammation are needed to facilitate early diagnosis and treatment of this debilitating disorder.

Therapeutic Interventions to Mitigate Mitochondrial Dysfunction and Oxidative Stress–Induced Damage in Patients with Bipolar Disorder

“…It is defined by disruptive depressive and manic or hypomanic episodes [25][26][27][28][29][30][31][32]. The two main categories of BD are type I (BD-I) and type II (BD-II) [33,34]. BD-I is characterized by at least one manic episode, involving increased activity, libido, and grandiose thinking, followed by a hypomanic or depressive episode [35][36][37][38].…”

[Retracted] Helicid Improves Lipopolysaccharide‐Induced Apoptosis of C6 Cells by Regulating SH2D5 DNA Methylation via the CytC/Caspase9/Caspase3 Signaling Pathway

“…Mitochondria are the energy source of cells and maintain life as a multifunctional organelle. Over and above the regulation of heat and programmed cell death, mitochondria are also involved in the production of adenine phosphate [ 7 , 8 ].…”

Can we prevent the neuroinflammation and neuroprogression produced by oxidative stress in euthymic bipolar patients, using mood stabilizers?

“…Thus, both, GSH-Px enzyme, which acts inside the mitochondria, but has low e ciency, and the CAT enzyme, which into the cytoplasm and is present in almost all cells, are highly e cient. Both can inhibit the lipid peroxidation, preventing any loss of membrane functions 10,32 .…”

“…The imbalance between the oxidative challenge (free radicals) and the body's antioxidant defense capacity is called oxidative stress. The set of substances that are called ROS are composed of the following elements: superoxide (O 2 •-), hydroxyl (OH•), hydrogen peroxide (H 2 O 2 ), nitric oxide (NO•), nitrogen dioxide (NO 2 ), and others, where most of them are formed through enzymatic and non-enzymatic reactions 9,10 . Therefore, the objective of this research was to evaluate four biomarkers of oxidative stress (SOD, GSH-Px, CAT, and TBA-RS) measured in peripheral blood samples, from 50 bipolar patients type I/II, that were in the euthymic phase for more than six months.…”