Translational Medicine
Open Access
ISSN: 2161-1025
ISSN: 2161-1025
Eminy H Y Lee
Accepted Abstracts: Transl Med
STAT1 plays an important role in inflammation and the innate immune response, but its role in the brain is less understood. Laminin-beta1 (LB1) is an extracellular matrix protein abundantly expressed in the hippocampus. The brain LB1 expression level is found increased in dementia patients and LB1 is transcriptionally regulated by STAT1. Here, we examined the role of STAT1 and LB1 in spatial learning and memory, and assessed the involvement of STAT1 and LB1 in mediating the memoryimpairing effect of amyloid-beta (Aβ). We found that water maze training down-regulated the expression of STAT1 and LB1 in rat hippocampal CA1 area, and spatial learning and memory function was enhanced in Stat1-knockout mice. Conversely, overexpression of STAT1 and LB1 both impaired water maze performance. Furthermore, Aβ impaired spatial learning and memory in association with a dose-dependent increase in STAT1 and LB1 expression, but knockdown of STAT1 and LB1 both reversed this effect of Aβ. This Aβ-induced increase in STAT1 and LB1 expression was also associated with a decrease in the expression of the N-methyl-D-aspartate receptor (NMDAR) subunits, NR1 and NR2B. Overexpression of NR1 or NR2B or exogenous application of NMDA reversed Aβ-induced learning and memory deficits as well as Aβ-induced STAT1 and LB1 expression. Our results demonstrate that STAT1 negatively regulates spatial learning and memory through transcriptional regulation of LB1 expression. We also identified a novel mechanism for Aβ pathogenesis through STAT1 induction. Notably, impairment of spatial learning and memory by this STAT1-mediated mechanism is independent of CREB signaling.
Eminy H Y Lee received her PhD degree from the Department of Neuroscience, UC San Diego, USA in 1982. She was appointed as an Associate Research Fellow by the Institute of Biomedical Sciences, Academia Sinica in Taiwan in 1983. She was promoted as a Research Fellow in 1989 and further promoted as a Distinguished Research Fellow in 2001. She is also a Chair Professor of National Cheng-chi University in Taiwan, where she received her BS degree. Her major research interests are mammalian learning/memory and neuroprotection. She has published nearly 100 papers in reputed journals and received many honors and awards.