ArticleNeuropathology and applied neurobiology2016
Extensive respiratory chain defects in inhibitory interneurones in patients with mitochondrial disease.
Article in Neuropathology and applied neurobiology, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 39 papers, 1 of them a synthesis that pooled it.
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Who cites it
39 citing papers in PubMed, 1 synthesis or guideline pooled it, 61 citations in OpenAlex.
- Comprehensive summary of mitochondrial DNA alterations in the postmortem human brain: A systematic review.EBioMedicine · 2022Pooled it
- The role of impaired mitochondrial function in neurological manifestations of mitochondrial diseases.Mammalian genome : official journal of the International Mammalian Genome Society · 2026Review
- Evaluation of an Integrated In Silico-In Vitro Pipeline for Predicting Mitochondrial Complex I-Mediated Neurotoxicity of Chlorpyrifos.Neurotoxicity research · 2026Article
- Pathophysiology and Prognostic Significance of Myoclonus in Hypoxic-Ischemic Encephalopathy.Journal of clinical neurophysiology : official publication of the American Electroencephalographic Society · 2026Review
- EEG, clinical, and MRI features of status epilepticus associated with mitochondrial diseases.Journal of neurology · 2026Article
- Epileptogenesis and Epilepsy Treatment: Advances in Mechanistic Understanding, Therapeutic Approaches, and Future Perspectives.International journal of molecular sciences · 2026Review
- Dysfunctional LHX6 pallido-subthalamic projections mediate epileptic events in a mouse model of Leigh syndrome.The Journal of clinical investigation · 2025Article
- Differential Sensitivity of Hippocampal GABAergic Neurons to Hypoxia and Ischemia-like Conditions Correlates with the Type of Calcium-Binding Protein Expressed.International journal of molecular sciences · 2025Article
- Delineating the mechanisms of cerebellar degeneration in paediatric and adult primary mitochondrial disease.Acta neuropathologica · 2025Article
- Single-nucleus transcriptomics reveals disease- and pathology-specific signatures in α-synucleinopathies.Brain : a journal of neurology · 2025Article
- Mitochondrial complex I deficiency stratifies idiopathic Parkinson's disease.Nature communications · 2024Article
- Delineating mechanisms underlying parvalbumin neuron impairment in different neurological and neurodegenerative disorders: the emerging role of mitochondrial dysfunction.Biochemical Society transactions · 2024Review
- Activation of Neurotoxic Astrocytes Due to Mitochondrial Dysfunction Triggered byInternational journal of biological sciences · 2024Article
- A novel mouse model of mitochondrial disease exhibits juvenile-onset severe neurological impairment due to parvalbumin cell mitochondrial dysfunction.Communications biology · 2023Article
- Elevated susceptibility to exogenous seizure triggers and impaired interneuron excitability in a mouse model of Leigh syndrome epilepsy.Neurobiology of disease · 2023Article
- Neurological Phenotypes in Mouse Models of Mitochondrial Disease and Relevance to Human Neuropathology.International journal of molecular sciences · 2023Review
- Astrocytic pathology in Alpers' syndrome.Acta neuropathologica communications · 2023Article
- Delineating selective vulnerability of inhibitory interneurons in Alpers' syndrome.Neuropathology and applied neurobiology · 2022Article
- TTC3-Mediated Protein Quality Control, A Potential Mechanism for Cognitive Impairment.Cellular and molecular neurobiology · 2022Review
- The metabolic basis of epilepsy.Nature reviews. Neurology · 2022Review
Corrections and comments
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Authors and funding
10 authors at 2 institutions in 1 country.
Funding
Abstract
aimsMitochondrial disorders are among the most frequently inherited cause of neurological disease and arise due to mutations in mitochondrial or nuclear DNA. Currently, we do not understand the specific involvement of certain brain regions or selective neuronal vulnerability in mitochondrial disease. Recent studies suggest γ-aminobutyric acid (GABA)-ergic interneurones are particularly susceptible to respiratory chain dysfunction. In this neuropathological study, we assess the impact of mitochondrial DNA defects on inhibitory interneurones in patients with mitochondrial disease.
methodsHistochemical, immunohistochemical and immunofluorescent assays were performed on post-mortem brain tissue from 10 patients and 10 age-matched control individuals. We applied a quantitative immunofluorescent method to interrogate complex I and IV protein expression in mitochondria within GABAergic interneurone populations in the frontal, temporal and occipital cortices. We also evaluated the density of inhibitory interneurones in serial sections to determine if cell loss was occurring.
resultsWe observed significant, global reductions in complex I expression within GABAergic interneurones in frontal, temporal and occipital cortices in the majority of patients. While complex IV expression is more variable, there is reduced expression in patients harbouring m.8344A>G point mutations and POLG mutations. In addition to the severe respiratory chain deficiencies observed in remaining interneurones, quantification of GABAergic cell density showed a dramatic reduction in cell density suggesting interneurone loss.
conclusionsWe propose that the combined loss of interneurones and severe respiratory deficiency in remaining interneurones contributes to impaired neuronal network oscillations and could underlie development of neurological deficits, such as cognitive impairment and epilepsy, in mitochondrial disease.
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