The Department of Biomedicine

BBB Seminar: Andrea Trentani

Regulation of hippocampal neurogenesis in healthy aging and Alzheimer’s disease

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Andrea Trentani
Department of Neurodegeneration Research, Neurology & GI Centre of Excellence for Drug Discovery, GlaxoSmithKline Pharmaceuticals, Harlow, UK

Our adult brain retains the capacity to generate new neurons through a process known as neurogenesis, which occurs in a few neurogenic microenvironments, including the subgranular layer of the dentate gyrus. Adult hippocampal neurogenesis takes place throughout the lifespan of mammals, including humans. It is actively involved in neural circuit plasticity and participates in memory formation, spatial learning, pattern separation, fear conditioning and anxiety. Rates of hippocampal neurogenesis steadily and dramatically decline with age. It is unclear, however, whether this sharp decrement is due to loss of neural progenitor cells, increased neural stem cell quiescence, impaired newborn cell survival, lengthening of the neuronal differentiation cascade or changes in the fate determination process. Here, the effects of aging on the proliferation, survival and differentiation of distinct neural progenitor cell populations in the hippocampus of transgenic mice from early adulthood to middle age will be described. Also changes of hippocampal neurogenesis in Alzheimer's disease (AD), an age-related, progressive and irreversible neurodegenerative disease characterized by progressive memory loss and impaired cognitive function, will be presented. A major hallmark of AD is the formation of beta-amyloid plaques, which have neurodegenerative properties and gradually accumulate in the brain causing inflammation, oxidative stress and eventually neuronal loss. Although it seems clear that adult hippocampal neurogenesis is dramatically reduced in the brains of old AD mice (APPswe/PS1), less is known about early dysfunctions when AD neuropathology is not extensive and neuronal loss still limited. These changes will be discussed and possible interventions aimed at attenuating AD-induced impairments will be set forth.

Host: Clive R. Bramham, Department of Biomedicine