The many roads to mitochondrial dysfunction in neuroimmune and neuropsychiatric disorders

Abstract

BackgroundMitochondrial dysfunction and defects in oxidative metabolism are a characteristic feature of many chronic illnesses not currently classified as mitochondrial diseases. Examples of such illnesses include bipolar disorder, multiple sclerosis, Parkinson’s disease, schizophrenia, depression, autism, and chronic fatigue syndrome.DiscussionWhile the majority of patients with multiple sclerosis appear to have widespread mitochondrial dysfunction and impaired ATP production, the findings in patients diagnosed with Parkinson’s disease, autism, depression, bipolar disorder schizophrenia and chronic fatigue syndrome are less consistent, likely reflecting the fact that these diagnoses do not represent a disease with a unitary pathogenesis and pathophysiology. However, investigations have revealed the presence of chronic oxidative stress to be an almost invariant finding in study cohorts of patients afforded each diagnosis. This state is characterized by elevated reactive oxygen and nitrogen species and/or reduced levels of glutathione, and goes hand in hand with chronic systemic inflammation with elevated levels of pro-inflammatory cytokines.SummaryThis paper details mechanisms by which elevated levels of reactive oxygen and nitrogen species together with elevated pro-inflammatory cytokines could conspire to pave a major road to the development of mitochondrial dysfunction and impaired oxidative metabolism seen in many patients diagnosed with these disorders.

Antioxidant Activity of Oral Administration of Rosmarinus Officinalis Leaves Extract on Rat's Hippocampus which Exposed to 6-Hydroxydopamine

“…There is considerable evidence suggesting that mitochondrial dysfunction and oxidative damages may play a role in the pathogenesis of PD (Hwang 2013;Morris and Berk 2015). Evidence of increase in lipid peroxidtion and oxidation of DNA and proteins has indeed been seen in the substantia nigra of patients affected with PD (Munoz et al 2012).…”

Gut Microbiota, Bacterial Translocation, and Interactions with Diet: Pathophysiological Links between Major Depressive Disorder and Non-Communicable Medical Comorbidities

“…This cascade can have downstream detrimental effects on mitochondrial bioenergetics, which is of relevance to mood disorders as well as disorders such as CFS and diabetes [44] . These pathophysiological events appear to be influenced by perturbations in the equilibrium of the gut microbiota and by disruptions in the gut barrier.…”

508. Perturbations in the Apoptotic Pathway and Mitochondrial Network Dynamics in Peripheral Blood Mononuclear Cells from Bipolar Disorder Patients

“…Our findings in PBMCs of patients with BD support a link between mitochondrial dysfunction and the pathophysiology of BD, and the fact that these changes are seen in peripheral PBMCs suggests that the pathophysiological processes active in the disorder are body-wide and implicate circulating factors. 69 Finally, understanding the mitochondrial network dynamics in BD and its interconnection with cellular signaling pathways may contribute to a more comprehensive understanding of the biological processes in this disease and may ultimately lead to the development of new treatment strategies. 70 …”