| First Author | Zou J | Year | 2016 |
| Journal | Brain Res | Volume | 1637 |
| Pages | 56-63 | PubMed ID | 26876740 |
| Mgi Jnum | J:230861 | Mgi Id | MGI:5766392 |
| Doi | 10.1016/j.brainres.2016.02.017 | Citation | Zou J, et al. (2016) Learning impairment by minimal cortical injury in a mouse model of Alzheimers disease. Brain Res 1637:56-63 |
| abstractText | Brain injury accelerates amyloid-beta (Abeta) deposits and exacerbates Alzheimers disease (AD). Accumulation of intracellular soluble Abeta impairs cognition prior to emergence of Abeta plaques. However, it is not known whether brain injury affects learning impairment attributable to intracellular soluble Abeta. We made a small injury by injecting glutamate into the parietal cortex in 3xTg AD mice of 4-5 months old, at which age soluble Abeta is accumulated without Abeta deposits. The size of glutamate-induced lesion was significantly larger than that of saline-injected control lesion. We reduced the relative difficulty of Morris water maze (MWM) task by repeating it twice, so that saline-injected 3xTg mice could perform as well as wild-type control mice. Under this condition, glutamate-injected 3xTg mice exhibited learning deficits. DNA microarray analysis revealed that 3 genes are upregulated, with one gene downregulated, more than 2 folds in the hippocampus. These 4 genes do not appear to be involved directly in learning but may be a part of signal cascade triggered by glutamate-induced small injury. Hippocampal content of soluble Abeta1-42 was increased in the glutamate 3xTg group. Facilitation of large-conductance calcium-activated potassium (BK) channel accompanied learning recovery in the saline-control 3xTg group in agreement with our previous reports, in which learning deficits attributable to intracellular Abeta were alleviated by facilitating BK channels. However, BK channel remained suppressed in the glutamate 3xTg group. It is suggested that glutamate-induced injury worsens learning by enhancing the toxicity of soluble Abeta or increasing its content per se. |
