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A role for adult TLX-positive neural stem cells in learning and behaviour.

Nature | Feb 21, 2008

Neurogenesis persists in the adult brain and can be regulated by a plethora of external stimuli, such as learning, memory, exercise, environment and stress. Although newly generated neurons are able to migrate and preferentially incorporate into the neural network, how these cells are molecularly regulated and whether they are required for any normal brain function are unresolved questions. The adult neural stem cell pool is composed of orphan nuclear receptor TLX-positive cells. Here, using genetic approaches in mice, we demonstrate that TLX (also called NR2E1) regulates adult neural stem cell proliferation in a cell-autonomous manner by controlling a defined genetic network implicated in cell proliferation and growth. Consequently, specific removal of TLX from the adult mouse brain through inducible recombination results in a significant reduction of stem cell proliferation and a marked decrement in spatial learning. In contrast, the resulting suppression of adult neurogenesis does not affect contextual fear conditioning, locomotion or diurnal rhythmic activities, indicating a more selective contribution of newly generated neurons to specific cognitive functions.

Pubmed ID: 18235445 RIS Download

Mesh terms: Aging | Animals | Behavior | Cell Proliferation | Conditioning (Psychology) | Fear | Hippocampus | Learning | Memory | Mice | Mice, Inbred C57BL | Neurons | Receptors, Cytoplasmic and Nuclear | Stem Cells

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Nuclear Receptor Signaling Atlas

Knowledge environment resource that accrues, develops, and communicates information that advances understanding of the structure, function, and role in disease of nuclear receptors (NRs) and coregulators. It specifically seeks to elucidate the roles played by NRs and coregulators in metabolism and the development of metabolic disorders (including type 2 diabetes, obesity, osteoporosis, and lipid dysregulation), as well as in cardiovascular disease, oncology, regenerative medicine and the effects of environmental agents on their actions. Resources include large validated data sets, access to reagents, new findings, a library of annotated prior publications in the field, and journal covering reviews and techniques.

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