Affiliations: [a] Department of Pathology, Case Western Reserve University, 2103 Cornell Road, Cleveland, Ohio 44106, USA | [b] Center for Neuroscience and Cell Biology of Coimbra, University of Coimbra, 3004-517, Coimbra, Portugal | [c] Pharmacology Research Laboratories I, Pharmaceutical Research Division, Takeda Chemical Industries Ltd., Osaka 532-8686, Japan | [x] Center for Neuroscience and Cell Biology, Institute of Physiology – Faculty of Medicine, University of Coimbra, 3004-504 Coimbra, Portugal | [y] Center for Neuroscience and Cell Biology, University of Coimbra, 3004-504 Coimbra, Portugal
Correspondence:
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Corresponding author: Xiongwei Zhu, Ph.D., Department of Pathology, Case Western Reserve University, 2103 Cornell Road, Cleveland, Ohio 44106, USA. Tel.: +1 216 368 5903; Fax: +1 216 368 8964; E-mail: [email protected].
Abstract: A number of mitochondrial and metabolic abnormalities were identified in the hippocampal neurons of Alzheimer disease compared to age-matched controls. Hippocampal neurons are the most vulnerable to disease-associated pathology (i.e., cell death and proteinaceous lesions) and contain numerous markers of oxidative stress. Interestingly we found that the levels of mitochondrial DNA and cytochrome oxidase-1 in these neurons are markedly increased compared with those of age-matched control brains, even though the number of mitochondria per neuron is decreased. We hypothesize that the increased levels of mitochondrial DNA and cytochrome oxidase-1 may reflect an attempt by oxidatively-challenged neurons to replicate mitochondria, albeit unsuccessfully, as a response to the energetic/oxidative stress. Indeed, in this context, numerous signs of mitosis are observed in pyramidal neurons. Mitotic signals that promote cell cycle re-entry might be expected to also signal the synthesis of new mitochondria. Alternatively, these abnormalities may indicate altered turnover of mitochondrial components as a result of reduced degradation of mitochondrial byproducts or altered mitochondrial transport that redistributes mitochondrial DNA and cytochrome oxidase-1 to the cell body.
