Mitochondrial DNA deletions and differential mitochondrial DNA content in Rhesus monkeys: Implications for aging

Mao, Peizhong; Gallagher, Patience; Nedungadi, Samira; Mańczak, Maria; Shirendeb, Ulziibat; Kohama, Steven G.; Ferguson, Betsy; Park, Byung; Reddy, P. Hemachandra

doi:10.1016/j.bbadis.2011.10.014

Cited by 20 publications

(12 citation statements)

References 43 publications

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“…To understand the mechanisms of aging, particularly the role of mtDNA in the brain, several researchers studied mtDNA, free radical production, and mitochondrial function in young and aged tissues from rodents, nonhuman primates, and humans [reviewed in 5, 7, 18, 19, 23 and 29, 30]. In aged tissues relative to young tissues from rodents, nonhuman primates, and humans, researchers found an accumulation of mtDNA defects, an increased production of ROS, and decreased mitochondrial function in the brain tissues from old rodents, nonhuman primates and humans [7, 18, 19, 29, 30], indicating that age-related accumulation of mtDNA defects is involved in aging. It has been reported that mitochondrial ETC is responsible for the transfer of electrons from NADH or FADH, to electron acceptors, and to oxygen, the final transfer of which leads to the production of H 2 O.…”

Section: Introductionmentioning

confidence: 99%

Mitochondria as a Therapeutic Target for Aging and Neurodegenerative Diseases

Reddy

2011

CAR

200

144

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Mitochondria are cytoplasmic organelles responsible for life and death. Extensive evidence from animal models, postmortem brain studies of and clinical studies of aging and neurodegenerative diseases suggests that mitochondrial function is defective in aging and neurodegenerative diseases, such as Alzheimer’s disease, Parkinson’s disease, Huntington’s disease, and amyotrophic lateral sclerosis. Several lines of research suggest that mitochondrial abnormalities, including defects in oxidative phosphorylation, increased accumulation of mitochondrial DNA defects, impaired calcium influx, accumulation of mutant proteins in mitochondria, and mitochondrial membrane potential dissipation are important cellular changes in both early and late-onset neurodegenerative diseases. Further, emerging evidence suggests that structural changes in mitochondria, including increased mitochondrial fragmentation and decreased mitochondrial fusion, are critical factors associated with mitochondrial dysfunction and cell death in aging and neurodegenerative diseases. This paper discusses research that elucidates features of mitochondria that are associated with cellular dysfunction in aging and neurodegenerative diseases and discusses mitochondrial structural and functional changes, and abnormal mitochondrial dynamics in neurodegenerative diseases. It also outlines mitochondria-targeted therapeutics in neurodegenerative diseases.

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Section: Introductionmentioning

confidence: 99%

Mitochondria as a Therapeutic Target for Aging and Neurodegenerative Diseases

Reddy

2011

CAR

200

144

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“…Associations between the mtDNA 4,977-bp common deletion load in the brain and neuropsychiatric disorders have also been reported [8,9,10,11]. The mtDNA common deletion levels have been shown to increase in the brain with advanced aging [12,13]. However, we have previously observed that the age-related increase in the common deletion in brain was significant in control subjects but was not observed in SZ [13,14,15,16,17].…”

Section: Introductionmentioning

confidence: 99%

Mitochondrial Complex I Deficiency in Schizophrenia and Bipolar Disorder and Medication Influence

Rollins¹,

Morgan²,

Hjelm³

et al. 2017

Complex Psychiatry

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Subjects with schizophrenia (SZ) and bipolar disorder (BD) show decreased protein and transcript levels for mitochondrial complex I. In vitro results suggest antipsychotic and antidepressant drugs may be responsible. We measured complex I activity in BD, SZ, and controls and presence of antipsychotic and antidepressant medications, mitochondrial DNA (mtDNA) copy number, and the mtDNA “common deletion” in the brain. Complex I activity in the prefrontal cortex was decreased by 45% in SZ compared to controls (p = 0.02), while no significant difference was found in BD. Complex I activity was significantly decreased (p = 0.01) in pooled cases (SZ and BD) that had detectable psychotropic medications and drugs compared to pooled cases with no detectable levels. Subjects with age at onset in their teens and psychotropic medications showed decreased (p < 0.05) complex I activity compared to subjects with an adult age at onset. Both SZ and BD groups displayed significant increases (p < 0.05) in mtDNA copy number compared to controls; however, common deletion burden was not altered. Complex I deficiency is found in SZ brain tissue, and psychotropic medications may play a role in mitochondrial dysfunction. Studies of medication-free first-episode psychosis patients are needed to elucidate whether mitochondrial pathophysiology occurs independent of medication effects.

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“…The adaptive response would partially compensate for mitochondrial dysfunction in these neurodegenerative diseases and would afford a human evolutionary response to shortage of ATP in the frontal cortex. This compensation also can be found in the brain of aged non-human primates [63].…”

Section: Definition and Pathology Of Dementia Withmentioning

confidence: 70%

Recent progress and concerns in dementia: Distinguishing Alzheimer's disease and dementia with Lewy bodies via biochemical markers in the cerebrospinal fluid

Mao¹

2012

ABC

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Dementia is mainly a neurodegenerative disorder involved in several systems, including central nervous system, endocrinology/metabolism system and circulatory system. Alzheimer's disease (AD) and dementia with Lewy bodies (DLB) are the most common forms of the dementia, accounting for 60% -80% and 10% -20% of all cases, respectively. DLB is defined by widespread neocortical, limbic and brainstem Lewy bodies but frequently accompanied by variable levels of AD pathology. This pathological and clinical overlap makes their differential diagnosis complicated. Recent advances in the identification of disease biomarkers now make it possible to detect and distinguish their pathology in the early or preclinical stage of the diseases, even in cognitively normal individuals. In addition to the key biomarkers (amyloid β or Aβ, tau and α-synuclein), neurotrophins such as cocaineand amphetamine-regulated transcript (CART) have also drawn attention due to their expressions and functions. This article summarizes the progress in the definition, pathology and diagnosis of dementia, with a focus on potential biochemical markers in the cerebrospinal fluid (CSF) in the differential diagnosis of the main forms of dementia. To prediction or early diagnosis of dementia, the role of specific and sensitive CSF biomarkers seems to be crucial in a routine clinical setting. The concerns and challenges in the biomarker field are also discussed.

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Mitochondrial DNA deletions and differential mitochondrial DNA content in Rhesus monkeys: Implications for aging

Cited by 20 publications

References 43 publications

Mitochondria as a Therapeutic Target for Aging and Neurodegenerative Diseases

Mitochondria as a Therapeutic Target for Aging and Neurodegenerative Diseases

Mitochondrial Complex I Deficiency in Schizophrenia and Bipolar Disorder and Medication Influence

Recent progress and concerns in dementia: Distinguishing Alzheimer's disease and dementia with Lewy bodies via biochemical markers in the cerebrospinal fluid

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