Genetic context drives age-related disparities in synaptic maintenance and structure across cortical and hippocampal neuronal circuits.

Autor: Heuer SE; The Jackson Laboratory, Bar Harbor, Maine, USA.; Tufts University Graduate School of Biomedical Sciences, Boston, Massachusetts, USA., Nickerson EW; The Jackson Laboratory, Bar Harbor, Maine, USA.; Tufts University Graduate School of Biomedical Sciences, Boston, Massachusetts, USA., Howell GR; The Jackson Laboratory, Bar Harbor, Maine, USA.; Tufts University Graduate School of Biomedical Sciences, Boston, Massachusetts, USA.; Graduate School of Biomedical Sciences and Engineering, University of Maine, Orono, Maine, USA., Bloss EB; The Jackson Laboratory, Bar Harbor, Maine, USA.; Tufts University Graduate School of Biomedical Sciences, Boston, Massachusetts, USA.; Graduate School of Biomedical Sciences and Engineering, University of Maine, Orono, Maine, USA.
Jazyk: angličtina
Zdroj: Aging cell [Aging Cell] 2024 Feb; Vol. 23 (2), pp. e14033. Date of Electronic Publication: 2023 Dec 21.
DOI: 10.1111/acel.14033
Abstrakt: The disconnection of neuronal circuitry through synaptic loss is presumed to be a major driver of age-related cognitive decline. Age-related cognitive decline is heterogeneous, yet whether genetic mechanisms differentiate successful from unsuccessful cognitive decline through maintenance or vulnerability of synaptic connections remains unknown. Previous work using rodent and primate models leveraged various techniques to imply that age-related synaptic loss is widespread on pyramidal cells in prefrontal cortex (PFC) circuits but absent on those in area CA1 of the hippocampus. Here, we examined the effect of aging on synapses on projection neurons forming a hippocampal-cortico-thalamic circuit important for spatial working memory tasks from two genetically distinct mouse strains that exhibit susceptibility (C57BL/6J) or resistance (PWK/PhJ) to cognitive decline during aging. Across both strains, synapse density on CA1-to-PFC projection neurons appeared completely intact with age. In contrast, we found synapse loss on PFC-to-nucleus reuniens (RE) projection neurons from aged C57BL/6J but not PWK/PhJ mice. Moreover, synapses from aged PWK/PhJ mice but not from C57BL/6J exhibited altered morphologies that suggest increased efficiency to drive depolarization in the parent dendrite. Our findings suggest resistance to age-related cognitive decline results in part by age-related synaptic adaptations, and identification of these mechanisms in PWK/PhJ mice could uncover new therapeutic targets for promoting successful cognitive aging and extending human health span.
(© 2023 The Authors. Aging Cell published by the Anatomical Society and John Wiley & Sons Ltd.)
Databáze: MEDLINE
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