Systemic Injection of Aged Blood Plasma in Adult C57BL/6 Mice Induces Neurophysiological Impairments in the Hippocampal CA1
Huffels, Christiaan F M; van Dijk, Roland E; Karst, Henk; Meye, Frank J; Hol, Elly M; Middeldorp, Jinte
(2022) Journal of Alzheimer's Disease, volume 89, issue 1, pp. 283 - 297
(Article)
Abstract
BACKGROUND: Aging is characterized by systemic alterations and forms an important risk factor for Alzheimer's disease (AD). Recently, it has been indicated that blood-borne factors present in the systemic milieu contribute to the aging process. Exposing young mice to aged blood plasma results in impaired neurogenesis and synaptic plasticity in
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the dentate gyrus, as well as impaired cognition. Vice versa, treating aged mice with young blood plasma rescues impairments associated with aging. OBJECTIVE: Whether blood-borne factors are sufficient to drive impairments outside the dentate gyrus, how they impact neurophysiology, and how the functional outcome compares to impairments found in mouse models for AD is still unclear. METHODS: Here, we treated adult mice with blood plasma from aged mice and assessed neurophysiological parameters in the hippocampal CA1. RESULTS: Mice treated with aged blood plasma show significantly impaired levels of long-term potentiation (LTP), similar to those present in APP/PS1 mice. These impaired levels of LTP in plasma-treated mice are associated with alterations in basic properties of glutamatergic transmission and the enhanced activity of voltage-gated Ca2+ channels. CONCLUSION: Together, the data presented in this study show that blood-borne factors are sufficient to drive neurophysiological impairments in the hippocampal CA1.
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Keywords: Aging, Alzheimer's disease, calcium, calcium channels, hippocampus, neuronal plasticity, plasma, General Neuroscience, Clinical Psychology, Geriatrics and Gerontology, Psychiatry and Mental health
ISSN: 1387-2877
Publisher: IOS Press
Note: Funding Information: This work was supported by ZonMw [733050816, 2017 –EMH, JM, and CFMH] and [73305054, 2015 - JM]: The Netherlands Organisation for Health Research and Development, Dementia Research and Innovation Program “Memorabel” with additional support from Alzheimer Nederland (73305054), and by UMC Utrecht Rudolf Magnus Young Talent fellowship 2017 (JM). The authors thank Nicky van Kronenburg for practical support. Funding Information: This work was supported by ZonMw [733050816, 2017 - EMH, JM, and CFMH] and [73305054, 2015 - JM]: The Netherlands Organisation for Health Research and Development, Dementia Research and Innovation Program Memorabel with additional support from Alzheimer Nederland (73305054), and by UMC Utrecht Rudolf Magnus Young Talent fellowship 2017 (JM). Publisher Copyright: © 2022 - IOS Press. All rights reserved.
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