Modulation of Adult Hippocampal Neurogenesis in ZnT3 Knockout Mice
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2019-01-07
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The adult hippocampus is unique in its ability to generate new neurons and presents an enticing target for developing our understanding of learning, memory and disease. While adult hippocampal neurogenesis appears to be regulated by extrinsic factors such as environmental enrichment and exercise, the mechanisms regulating the proliferation, differentiation and survival of adult-born neurons are unclear. Synaptic zinc, which is packaged into vesicles by zinc transporter 3 (ZnT3), is a neurotransmitter capable of modulating a variety of receptors. Previously, our lab observed that ZnT3 knock-out mice exposed to environmental enrichment do not show increases in neurogenesis and, moreover, that these mice did not show increases in brain-derived neurotrophic factor (BDNF), a neurotrophin whose signalling through its receptor, TrkB, is essential in neurogenesis. We examined whether a TrkB agonist, 7,8-dihydroxyflavone (DHF), was sufficient to recover neurogenesis in ZnT3 knock-out mice, as well as how neurogenesis was affected by exercise and DHF treatment in ZnT3 knock-out and wild-type mice. The results of our study suggest that the loss of synaptic zinc in ZnT3 knock-out mice has a profound effect on proliferation, but not differentiation, and highlights the importance of studying each stage of neurogenesis in order to understand the specific effects of an intervention.
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Bihelek, N. (2019). Modulation of adult hippocampal neurogenesis in ZnT3 knockout mice (Master's thesis, University of Calgary, Calgary, Canada). Retrieved from https://prism.ucalgary.ca..