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OPA1 deficiency accelerates hippocampal synaptic remodelling and age-related deficits in learning and memory

Bevan, Ryan J., Williams, Pete A., Waters, Caroline T., Thirgood, Rebecca, Mui, Amanda, Seto, Sharon, Good, Mark, Morgan, James E., Votruba, Marcela and Erchova, Irina 2020. OPA1 deficiency accelerates hippocampal synaptic remodelling and age-related deficits in learning and memory. Brain Communications 2 (2) 10.1093/braincomms/fcaa101

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Abstract

A healthy mitochondrial network is essential for the maintenance of neuronal synaptic integrity. Mitochondrial and metabolic dysfunction contributes to the pathogenesis of many neurodegenerative diseases including dementia. OPA1 is the master regulator of mitochondrial fusion and fission and is likely to play an important role during neurodegenerative events. To explore this, we quantified hippocampal dendritic and synaptic integrity and the learning and memory performance of aged Opa1 haploinsufficient mice carrying the Opa1Q285X mutation (B6; C3-Opa1Q285STOP; Opa1+/−). We demonstrate that heterozygous loss of Opa1 results in premature age-related loss of spines in hippocampal pyramidal CA1 neurons and a reduction in synaptic density in the hippocampus. This loss is associated with subtle memory deficits in both spatial novelty and object recognition. We hypothesize that metabolic failure to maintain normal neuronal activity at the level of a single spine leads to premature age-related memory deficits. These results highlight the importance of mitochondrial homeostasis for maintenance of neuronal function during ageing.

Item Type: Article
Date Type: Published Online
Status: In Press
Schools: Optometry and Vision Sciences
Psychology
Publisher: Oxford University Press
ISSN: 2632-1297
Funders: MRC
Date of First Compliant Deposit: 19 October 2020
Date of Acceptance: 27 May 2020
Last Modified: 03 Dec 2020 17:15
URI: http://orca.cf.ac.uk/id/eprint/135719

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