Previous research emphasized the impact of
traumatic brain injury on
cholinergic systems and associated cognitive functions. Here we addressed the converse question: Because of the available evidence indicating cognitive and neuronal vulnerabilities in humans expressing low-capacity
cholinergic systems or with declining
cholinergic systems, do
injuries cause more severe
cognitive decline in such subjects, and what
cholinergic mechanisms contribute to such vulnerability? Using mice heterozygous for the
choline transporter (CHT+/- mice) as a model for a limited
cholinergic capacity, we investigated the cognitive and neuronal consequences of repeated,
mild concussion injuries (rmCc). After five rmCc, and compared with wild type (WT) mice, CHT+/- mice exhibited severe and lasting impairments in sustained attention performance, consistent with effects of
cholinergic losses on attention. However, rmCc did not affect the integrity of neuronal cell bodies and did not alter the density of cortical synapses. As a cellular mechanism potentially responsible for the attentional impairment in CHT+/- mice, we found that rmCc nearly completely attenuated performance-associated, CHT-mediated
choline transport. These results predict that subjects with an already vulnerable
cholinergic system will experience severe and lasting cognitive-
cholinergic effects after even relatively mild
injuries. If confirmed in humans, such subjects may be excluded from, or receive special protection against, activities involving injury risk. Moreover, the treatment and long-term outcome of
traumatic brain injuries may benefit from determining the status of
cholinergic systems and associated cognitive functions. (PsycINFO Database Record (c) 2019 APA, all rights reserved).