Adult Neural Stem Cell Proliferation is Not Altered in Transgenic Mice Over-expressing BDNF or Mutant Huntingtin in Forebrain
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چکیده
Stem cells in the adult brain subventricular zone (SVZ) generate new neurons that migrate to the olfactory bulb. About half of the new neurons survive and become functional interneurons. SVZ stem cells are being studied to discover if there are ways to enhance the survival of adult-born neurons, and if they can be used to replace neurons in damaged brain areas. In transgenic mouse models of Huntington’s disease (HD), survival of new olfactory neurons is reduced. Crossing this group with mice over-expressing the growth factor brain-derived neurotrophic factor (BDNF) may increase neuron survival. Before testing for neuron survival effects, we quantified SVZ cell proliferation to determine if transgene expression affected SVZ stem cell proliferation. Four groups of mice (BDNF over-expressers, HD mice, two control strains) were analyzed. Mice were given the mitotic cell marker bromodeoxyuridine (BrdU), euthanized 4 hours later, and labeled SVZ cells were counted. The results indicate that neither increased BDNF expression or expression of a human HD mutation have any significant effect on endogenous SVZ cell proliferation in adult mice.
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Page 221 Huntington’s disease (HD) is an inherited neurodegenerative disorder caused by an expansion of the polyglutamine tract in the aminoterminal region of huntingtin. The mutant protein attenuates the action of striatal brain-derived neurotrophic factor (BDNF), which is a critical step in the pathogenesis of HD. Overexpression of BDNF in the forebrain rescues many symptoms and slows progres...
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تاریخ انتشار 2012