MITOCHONDRIA IN DEVELOPING BRAIN: CONTRIBUTION OF DEVIATIONS TO HIGHER SUSCEPTIBILITY TO NEURODEGENERATION IN LATTER PERIODS OF LIFE

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Abstract

It has been proven that the preclinical period of the sporadic (> 95% of cases) form of Alzheimer's disease (AD) can last for decades, but the question of when the disease begins to develop and what contributes to it remains open. It is assumed that vulnerability to AD can be facilitated by the anatomical and functional parameters of the brain that form early in life. This is also supported by the results of our studies on accelerated senescence OXYS rats, a unique model of AD. The delay in brain maturation revealed in them is associated with insufficient glial support, a key regulator of neural network functioning, and the development of AD signs in OXYS rats is preceded and accompanied by mitochondrial dysfunction. This allowed us to raise the question of whether the structural and functional features of mitochondria can influence the process of brain maturation and thus determine the predisposition to the further development of AD signs. In this study, we compared mitochondrial biogenesis, their traffic and structural state in neuronal cell bodies, axonal and dendritic processes, and the activity of mitochondrial dynamics processes in the prefrontal cortex and hippocampus of OXYS and Wistar rats (control) during the period of brain maturation completion (from birth to 20 days of age). Changes in the number and ultrastructural parameters of mitochondria were compared with the activity of dynamics processes, which was assessed by the frequency of occurrence of mitochondria undergoing fusion or fission, the content of the key protein of their biogenesis PGC- 1a and proteins mediating mitochondrial dynamics (mitofusins MFN1 and MFN2, dynamin- 1- like protein DRP1). In OXYS rats, abnormalities in the formation of the mitochondrial apparatus in the early postnatal period were revealed, which can contribute to the delay in brain maturation of OXYS rats, promote mitochondrial dysfunction, decreased synapse density and, ultimately, neuronal death and the development of early neurodegenerative changes in the future.

About the authors

N. A. Stefanova

Institute of Cytology and Genetics, Siberian Branch of the Russian Academy of Sciences

Email: stefanovam@mail.ru
Novosibirsk, Russia

N. A. Muraleva

Institute of Cytology and Genetics, Siberian Branch of the Russian Academy of Sciences

Novosibirsk, Russia

D. V. Sityaeva

Institute of Cytology and Genetics, Siberian Branch of the Russian Academy of Sciences

Novosibirsk, Russia

M. A. Tyumentsev

University of Tennessee Health Science Center

Memphis, USA

N. G. Kolosova

Institute of Cytology and Genetics, Siberian Branch of the Russian Academy of Sciences

Novosibirsk, Russia

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