High-frequency head impact causes chronic synaptic adaptation and long-term cognitive impairment in mice.

Autor: Sloley SS; Interdisciplinary Program in Neuroscience, Georgetown University Medical Center, Washington, DC, USA.; Department of Neuroscience, Georgetown University Medical Center, Washington, DC, USA., Main BS; Department of Neuroscience, Georgetown University Medical Center, Washington, DC, USA., Winston CN; Interdisciplinary Program in Neuroscience, Georgetown University Medical Center, Washington, DC, USA.; Department of Neuroscience, Georgetown University Medical Center, Washington, DC, USA., Harvey AC; Department of Neuroscience, Georgetown University Medical Center, Washington, DC, USA., Kaganovich A; Laboratory of Neurogenetics, National Institute of Aging, Bethesda, MD, USA., Korthas HT; Interdisciplinary Program in Neuroscience, Georgetown University Medical Center, Washington, DC, USA.; Department of Neuroscience, Georgetown University Medical Center, Washington, DC, USA., Caccavano AP; Interdisciplinary Program in Neuroscience, Georgetown University Medical Center, Washington, DC, USA.; Department of Pharmacology and Physiology, Georgetown University Medical Center, Washington, DC, USA., Zapple DN; Department of Neuroscience, Georgetown University Medical Center, Washington, DC, USA., Wu JY; Interdisciplinary Program in Neuroscience, Georgetown University Medical Center, Washington, DC, USA.; Department of Neuroscience, Georgetown University Medical Center, Washington, DC, USA., Partridge JG; Interdisciplinary Program in Neuroscience, Georgetown University Medical Center, Washington, DC, USA.; Department of Pharmacology and Physiology, Georgetown University Medical Center, Washington, DC, USA., Cookson MR; Laboratory of Neurogenetics, National Institute of Aging, Bethesda, MD, USA., Vicini S; Interdisciplinary Program in Neuroscience, Georgetown University Medical Center, Washington, DC, USA.; Department of Pharmacology and Physiology, Georgetown University Medical Center, Washington, DC, USA., Burns MP; Interdisciplinary Program in Neuroscience, Georgetown University Medical Center, Washington, DC, USA. mark.burns@georgetown.edu.; Department of Neuroscience, Georgetown University Medical Center, Washington, DC, USA. mark.burns@georgetown.edu.
Jazyk: angličtina
Zdroj: Nature communications [Nat Commun] 2021 May 10; Vol. 12 (1), pp. 2613. Date of Electronic Publication: 2021 May 10.
DOI: 10.1038/s41467-021-22744-6
Abstrakt: Repeated head impact exposure can cause memory and behavioral impairments. Here, we report that exposure to non-damaging, but high frequency, head impacts can alter brain function in mice through synaptic adaptation. High frequency head impact mice develop chronic cognitive impairments in the absence of traditional brain trauma pathology, and transcriptomic profiling of mouse and human chronic traumatic encephalopathy brain reveal that synapses are strongly affected by head impact. Electrophysiological analysis shows that high frequency head impacts cause chronic modification of the AMPA/NMDA ratio in neurons that underlie the changes to cognition. To demonstrate that synaptic adaptation is caused by head impact-induced glutamate release, we pretreated mice with memantine prior to head impact. Memantine prevents the development of the key transcriptomic and electrophysiological signatures of high frequency head impact, and averts cognitive dysfunction. These data reveal synapses as a target of high frequency head impact in human and mouse brain, and that this physiological adaptation in response to head impact is sufficient to induce chronic cognitive impairment in mice.
Databáze: MEDLINE
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