Somatic mutations in neurons during aging and neurodegeneration

The nervous system is composed of a large variety of neurons with a diverse array of morphological and functional properties. This heterogeneity is essential for the construction and maintenance of a distinct set of neural networks with unique characteristics. Accumulating evidence now indicates tha...

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Bibliographic Details
Published in:Acta neuropathologica Vol. 135; no. 6; pp. 811 - 826
Main Authors: Verheijen, Bert M., Vermulst, Marc, van Leeuwen, Fred W.
Format: Journal Article
Language:English
Published: Berlin/Heidelberg Springer Berlin Heidelberg 01.06.2018
Springer
Springer Nature B.V
Subjects:
Aging
Aging - genetics
Animals
Genetic aspects
Genomics
Humans
Hypothalamus
Medicine
Medicine & Public Health
Mosaicism
Mutation
Nerve Degeneration - genetics
Nervous system
Neural networks
Neurodegeneration
Neurodegenerative Diseases - genetics
Neurons
Neurophysiology
Neurosciences
Pathology
Physiological aspects
Pituitary
Pituitary (posterior)
Population genetics
Review
Somatic mutations
Neurodegeneration
Neuronal development
Aging
Genome integrity
Somatic brain mosaicism
Neurological disorders
ISSN:0001-6322, 1432-0533, 1432-0533
Online Access:Get full text
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Summary:The nervous system is composed of a large variety of neurons with a diverse array of morphological and functional properties. This heterogeneity is essential for the construction and maintenance of a distinct set of neural networks with unique characteristics. Accumulating evidence now indicates that neurons do not only differ at a functional level, but also at the genomic level. These genomic discrepancies seem to be the result of somatic mutations that emerge in nervous tissue during development and aging. Ultimately, these mutations bring about a genetically heterogeneous population of neurons, a phenomenon that is commonly referred to as “somatic brain mosaicism”. Improved understanding of the development and consequences of somatic brain mosaicism is crucial to understand the impact of somatic mutations on neuronal function in human aging and disease. Here, we highlight a number of topics related to somatic brain mosaicism, including some early experimental evidence for somatic mutations in post-mitotic neurons of the hypothalamo-neurohypophyseal system. We propose that age-related somatic mutations are particularly interesting, because aging is a major risk factor for a variety of neuronal diseases, including Alzheimer’s disease. We highlight potential links between somatic mutations and the development of these diseases and argue that recent advances in single-cell genomics and in vivo physiology have now finally made it possible to dissect the origins and consequences of neuronal mutations in unprecedented detail.
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ISSN:0001-6322
1432-0533
1432-0533
DOI:10.1007/s00401-018-1850-y