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Mitochondria with Morphology Characteristic for Alzheimer’s Disease Patients Are Found in the Brain of OXYS Rats

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Abstract

Growing evidence suggests that mitochondrial dysfunction is closely linked to the pathogenesis of sporadic Alzheimer’s disease (AD). One of the key contributors to various aspects of AD pathogenesis, along with metabolic dysfunction, is mitochondrial dynamics, involving balance between fusion and fission, which regulates mitochondrial number and morphology in response to changes in cellular energy demand. Recently, Zhang et al. ((2016) Sci. Rep., 6, 18725) described a previously unknown mitochondrial phenotype manifesting as elongated chain-linked mitochondria termed “mitochondria-on-a-string” (MOAS) in brain tissue from AD patients and mouse models of AD. The authors associated this phenotype with fission arrest, but implications of MOAS formation in AD pathogenesis remain to be understood. Here we analyze the presence and number of MOAS in the brain of OXYS rats simulating key signs of sporadic AD. Using electron microscopy, we found MOAS in OXYS prefrontal cortex neuropil in all stages of AD-like pathology, including mani-festation (5-month-old rats) and progression (12–18-month-old rats). The most pronounced elevation of MOAS content (8–fold) in OXYS rats compared to Wistar controls was found at the preclinical stage (20 days) on the background of decreased numbers of non-MOAS elongated mitochondria. From the age of 20 days through 18 months, the percentage of MOAS-containing neuronal processes increased from 1.7 to 8.3% in Wistar and from 13.9 to 16% in OXYS rats. Our results support the importance of the disruption of mitochondrial dynamics in AD pathogenesis and corroborate the existence of a causal link between impaired mitochondrial dynamics and formation of the distinctive phenotype of “mitochondria-on-a-sting”.

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Abbreviations

Aβ:

amyloid beta

AD:

Alzheimer’s disease

MOAS:

mitochondria-on-a-string

ROS:

reactive oxygen species

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Authors and Affiliations

  1. Institute of Cytology and Genetics, Siberian Branch of the Russian Academy of Sciences, 630090, Novosibirsk, Russia

    M. A. Tyumentsev, N. A. Stefanova, E. V. Kiseleva & N. G. Kolosova

  2. Novosibirsk State University, 630090, Novosibirsk, Russia

    N. G. Kolosova

Authors
  1. M. A. Tyumentsev
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  2. N. A. Stefanova
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  3. E. V. Kiseleva
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  4. N. G. Kolosova
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Corresponding author

Correspondence to N. G. Kolosova.

Additional information

Original Russian Text © M. A. Tyumentsev, N. A. Stefanova, E. V. Kiseleva, N. G. Kolosova, 2018, published in Biokhimiya, 2018, Vol. 83, No. 9, pp. 1361–1367.

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Tyumentsev, M.A., Stefanova, N.A., Kiseleva, E.V. et al. Mitochondria with Morphology Characteristic for Alzheimer’s Disease Patients Are Found in the Brain of OXYS Rats. Biochemistry Moscow 83, 1083–1088 (2018). https://doi.org/10.1134/S0006297918090109

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  • DOI: https://doi.org/10.1134/S0006297918090109

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