Persistent upregulation of brain phospho‐tau is accompanied by elevated hippocampal synaptic excitability and altered Ca2+ handling, following single or repeated closed‐head concussive impacts
Year: 2020
Type: article
Abstract: Background Traumatic brain injury (TBI) is of widespread clinical concern and a significant risk factor for Alzheimer’s‐like dementia (AD). Notably, repeated concussions, vs. single concussions, have been shown to result in worsened and sustained neurological symptoms, including impaired cognition and histopathology similar to that observed in AD. Method To assess and compare the long‐term effects of single or repeated concussive impacts on phospho‐tau, an established marker of neurodegeneration, along with mediators of memory encoding such as synaptic transmission and plasticity, and cellular Ca2+ signaling, we utilized a closed‐head controlled cortical impact (CCI) approach which closely replicates the mode of injury in clinical cases. We examined rats 30 days post‐CCI to measure persistent injury effects. Groups received either a sham procedure, a single impact, or three successive impacts at 48 hour intervals. After 30 days, hippocampal slices were fixed and immunostained for phospho‐tau species, or prepared for 2‐photon Ca2+ imaging and electrophysiological recordings. Result Phospho‐tau staining was elevated in the repeated concussion group, an effect which was accompanied by a decreased ryanodine receptor‐mediated Ca2+ response. In both concussion groups, hippocampal circuits showed increased synaptic responsivity upon Schaffer collateral stimulation compared to sham animals, indicating sustained hyperexcitability in hippocampal circuitry. This synaptic potentiation was not accompanied by LTP deficits, but basal Ca2+ and voltage‐gated Ca2+ signals were elevated in both concussion groups. Conclusion Repeated concussion may lead to a similarly persistent upregulation of phospho‐tau, along with upregulation of select excitatory hippocampal synapses, possibly through changes in postsynaptic Ca2+ signaling/regulation, which, along with the aberrant histopathology observed, may form a basis for the detrimental long‐term cognitive symptoms and conversion to AD.
Source: Alzheimer s & Dementia
DOI: 10.1002/alz.047635
Author: John McDaid
Institution: Rosalind Franklin University of Medicine and Science
Language: English
Subfield: Epidemiology
Field: Medicine
Domain: Health Sciences
Open Access status: bronze
OpenAlex ID: W3111444380