Poster abstracts
Poster number 71 submitted by Kiara Bahamonde
Trpm2 channels mitigate chronic cognitive impairments following mild repetitive traumatic brain injury.
Kiara E. Bahamonde (Neuroscience Graduate Program ), Rachel E. Carpenter (Department of Neurological Surgery, The Ohio State University College of Medicine), Derrick D. Dedino (Department of Neurological Surgery, The Ohio State University College of Medicine), Declan M. Faherty, James E. Orfila (Department of Neurological Surgery, The Ohio State University College of Medicine), Paco S. Herson (Department of Neurological Surgery, The Ohio State University College of Medicine)
Abstract:
Traumatic brain injuries (TBI) affect millions of individuals each year and 70-90% of diagnosed TBIs are mild. Persistent cumulative impairments may arise from repeated mild TBIs (RmTBI), with cognitive dysfunction being the primary cause of disability after RmTBI. A promising therapeutic mechanism for cognitive restoration in males following brain injury are Trpm2 channels. Trpm2 channels are non-selective cation channels widely expressed in the brain and become activated during oxidative stress. Once activated, Trpm2 channels stay open and exacerbate hippocampal dysfunction and memory impairment after injury. Thus, I hypothesize that the inhibition of Trpm2 channel activation via pharmacological intervention or genetic knockdown after RmTBI will restore cognitive function in males at both subacute and chronic timepoints. This study uses hippocampal extracellular field recordings from the CA3 to CA1 Schaffer collaterals as a cellular correlate for learning and memory. Previous data from our lab shows that in a moderate/severe TBI model, administration of a Trpm2 antagonist ameliorated cognitive dysfunction and preserved hippocampal synaptic plasticity at 7 and 30 days post-injury (DPI). Preliminary data collected in male C57BL/6 mice who sustained RmTBI displayed impaired memory in contextual fear conditioning (CFC) at 7 DPI (41.85% ± 6.063, n=9) compared to the control group (77.04% ± 3.827, n=9). Additionally, these memory impairments present in CFC persisted in the RmTBI group at 30DPI (29.33% ± 5.551, n=10). Recordings were then performed in acute hippocampal slices from whole-body Trpm2 knockout male mice harvested 30 days after RmTBI. Injured Trpm2KO mice displayed neuroprotection in long-term potentiation (LTP) 30 DPI (168.7 ± 10.32%, n=6) while wildtype mice who were subjected to RmTBI had impaired LTP (120.6 ± 12.96%, n=5). In summary, preliminary data suggests that chronic cognitive impairments and hippocampal dysfunction caused by RmTBI in males can be mitigated by the inhibition of Trpm2 channels.
Keywords: Traumatic Brain Injury, Electrophysiology, Hippocampal plasticity