Deficits in learning and memory are prominent features of many mental disorders. Understanding molecular mechanisms responsible for learning and memory are key to the development of therapies to improve learning and memory in the treatment of mental illness. Recent studies lead to the exciting idea that newly generated neurons in the adult dentate gyrus (DG) of the hippocampus may play a role in neural plasticity including hippocampal-dependent memory formation. Adult neurogenesis occurs in the DG of the mammalian brains including adult human brain under physiological conditions and newly generated neurons functionally integrate to the DG. Many factors, including depression and other mental illness may adversely affect hippocampal adult neurogenesis. In contrast, treatment with anti-depressants and exercise, an effective means to treat depression, enhance adult neurogenesis in the DG. Consequently, elucidation of basic molecular mechanisms regulating adult hippocampal neurogenesis and generation of definitive evidence supporting a role for adult neurogenesis in hippocampal-dependent memory formation is a critical and timely issue for mental health research. Although many studies have assessed the role of adult neurogenesis in hippocampal-dependent learning and memory, the results have been inconsistent, making it still highly controversial whether adult neurogenesis contributes to hippocampus-dependent memory formation. This proposal will test the hypothesis that ERK5 signaling-mediated adult neurogenesis plays a critical role in some but not all forms of hippocampal- dependent learning and memory.
Our proposed studies are likely to provide new insights concerning signal transduction mechanisms regulating adult neurogenesis, and may lead to new insights to the development of therapies to improve learning and memory in the treatment of mental illness.
|Engstrom, Anna K; Snyder, Jessica M; Maeda, Nobuyo et al. (2017) Correction to: Gene-environment interaction between lead and Apolipoprotein E4 causes cognitive behavior deficits in mice. Mol Neurodegener 12:81|
|Engstrom, Anna K; Xia, Zhengui (2017) Lead exposure in late adolescence through adulthood impairs short-term spatial memory and the neuronal differentiation of adult-born cells in C57BL/6 male mice. Neurosci Lett 661:108-113|
|Wang, Hao; Engstrom, Anna K; Xia, Zhengui (2017) Cadmium impairs the survival and proliferation of cultured adult subventricular neural stem cells through activation of the JNK and p38 MAP kinases. Toxicology 380:30-37|
|Engstrom, Anna K; Snyder, Jessica M; Maeda, Nobuyo et al. (2017) Gene-environment interaction between lead and Apolipoprotein E4 causes cognitive behavior deficits in mice. Mol Neurodegener 12:14|
|Wang, Wenbin; Lu, Song; Li, Tan et al. (2015) Inducible activation of ERK5 MAP kinase enhances adult neurogenesis in the olfactory bulb and improves olfactory function. J Neurosci 35:7833-49|
|Engstrom, Anna; Wang, Hao; Xia, Zhengui (2015) Lead decreases cell survival, proliferation, and neuronal differentiation of primary cultured adult neural precursor cells through activation of the JNK and p38 MAP kinases. Toxicol In Vitro 29:1146-55|
|Luo, Jie; Chen, Xuanmao; Pan, Yung-Wei et al. (2015) The type 3 adenylyl cyclase is required for the survival and maturation of newly generated granule cells in the olfactory bulb. PLoS One 10:e0122057|
|Zou, Junhui; Wang, Wenbin; Pan, Yung-Wei et al. (2015) Methods to measure olfactory behavior in mice. Curr Protoc Toxicol 63:11.18.1-21|
|Wang, Wenbin; Pan, Yung-Wei; Zou, Junhui et al. (2014) Genetic activation of ERK5 MAP kinase enhances adult neurogenesis and extends hippocampus-dependent long-term memory. J Neurosci 34:2130-47|
|Zou, Junhui; Storm, Daniel R; Xia, Zhengui (2013) Conditional deletion of ERK5 MAP kinase in the nervous system impairs pheromone information processing and pheromone-evoked behaviors. PLoS One 8:e76901|
Showing the most recent 10 out of 26 publications