| First Author | Sangadi DK | Year | 2024 |
| Journal | Exp Neurol | Volume | 372 |
| Pages | 114647 | PubMed ID | 38070724 |
| Mgi Jnum | J:353508 | Mgi Id | MGI:7569977 |
| Doi | 10.1016/j.expneurol.2023.114647 | Citation | Sangadi DK, et al. (2024) Enhancing cognitive function in chronic TBI: The Role of alpha7 nicotinic acetylcholine receptor modulation. Exp Neurol 372:114647 |
| abstractText | Traumatic brain injury (TBI) results in several pathological changes within the hippocampus that result in adverse effects on learning and memory. Therapeutic strategies to enhance learning and memory after TBI are still in the early stages of clinical development. One strategy is to target the alpha7 nicotinic acetylcholine receptor (nAChR), which is highly expressed in the hippocampus and contributes to the formation of long-term memory. In our previous study, we found that AVL-3288, a positive allosteric modulator of the alpha7 nAChR, improved cognitive recovery in rats after moderate fluid-percussion injury (FPI). However, whether AVL-3288 improved cognitive recovery specifically through the alpha7 nAChR was not definitively determined. In this study we utilized Chrna7 knockout mice and compared their recovery to wild-type mice treated with AVL-3288 after TBI. We hypothesized that AVL-3288 treatment would improve learning and memory in wild-type mice, but not Chrna7(-/-) mice after TBI. Adult male C57BL/6 wild-type and Chrna7(-/-) mice received sham surgery or moderate controlled cortical impact (CCI) and recovered for 3 months. Mice were then treated with vehicle or AVL-3288 at 30 min prior to contextual fear conditioning. At 3 months after CCI, expression of alpha7 nAChR, choline acetyltransferase (ChAT), high-affinity choline transporter (ChT), and vesicular acetylcholine transporter (VAChT) were found to be significantly decreased in the hippocampus. Treatment of wild-type mice at 3 months after CCI with AVL-3288 significantly improved cue and contextual fear conditioning, whereas no beneficial effects were observed in Chrna7(-/-) mice. Parietal cortex and hippocampal atrophy were not improved with AVL-3288 treatment in either wild-type or Chrna7(-/-) mice. Our results indicate that AVL-3288 improves cognition during the chronic recovery phase of TBI through modulation of the alpha7 nAChR. |
