Neurogenesis in Huntington's disease: Can studying adult neurogenesis lead to the development of new therapeutic strategies?
Summary of "Neurogenesis in Huntington's disease: Can studying adult neurogenesis lead to the development of new therapeutic strategies?"
Huntington's disease (HD) is an autosomal dominant neurodegenerative disorder caused by an unstable expansion of CAG repeats in the HD gene. The symptoms include cognitive dysfunction and severe motor impairments. The neuropathology is characterized by neuronal loss mainly in the striatum and cortex, although other regions including the hippocampus are also affected. In this review we discuss the different mouse models of HD, and how the process of neurogenesis in the dentate gyrus (DG) of the hippocampus and the subventricular zone (SVZ) is affected in each. Deficits in adult hippocampal neurogenesis have been repeatedly shown in different genetic models of HD, raising the possibility that an impairment of the neurogenic process might underlie some of the cognitive deficits associated with this neurodegenerative disorder. On the other hand, an increase in SVZ neurogenesis has been observed in human HD brains while no differences in SVZ cell proliferation have been detected in the mouse models. In this review we will discuss the discrepancies between these findings as well as the several mechanisms that might contribute to a dysregulation of adult neurogenesis in HD. Finally, we will provide an overview of the various therapeutic strategies aimed at stimulating the endogenous neurogenic capacity that have been tested in HD genetic models. Ultimately, the insights obtained from these and future studies will greatly improve our understanding of the cognitive impairment characteristic of HD.
Division of Medical Sciences, Island Medical Program, University of Victoria, Victoria, BC, Canada.
This article was published in the following journal.
Name: Brain research
- PubMed Source: http://www.ncbi.nlm.nih.gov/pubmed/21742312
- DOI: http://dx.doi.org/10.1016/j.brainres.2011.06.040
New neurons are generated throughout life in distinct regions of the mammalian brain. This process, called adult neurogenesis, has been implicated in physiological brain function, and failing or alter...
Adult neurogenesis is now widely accepted as an important contributor to hippocampal integrity and function but also dysfunction when adult neurogenesis is affected in neuropsychiatric diseases such a...
Adult neurogenesis is an important therapeutic target in treating neurological disorders. Adult neurogenesis takes place in two regions of the brain: Subventricular zone and dentate gyrus in the hippo...
The morphogenesis of the dentate gyrus (DG) of the hippocampus primarily occurs postnatally, and the DG is one of the few regions of continuous neurogenesis in the adult brain. Radial glial cells (RGC...
Cumulative evidence has indicated that there is an important role for adult hippocampal neurogenesis in cognitive function. With the increasing prevalence of cognitive decline associated with neurodeg...
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The purpose of this trial is to study early brain and behavioral changes in people who have the gene expansion for Huntington's disease, but are currently healthy and have no symptoms.
This study is being conducted to determine the safety and tolerability of Dimebon in people with Huntington's disease after short-term exposure (one week) and after longer exposure (three ...
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Medical and Biotech [MESH] Definitions
Nucleus in the NEOSTRIATUM of bird brains that sends signals for song production and receives auditory input. In some adult SONGBIRDS, research has shown that the size of this nucleus changes seasonally and that it exhibits neurogenesis.
Formation of NEURONS which involves the differentiation and division of STEM CELLS in which one or both of the daughter cells become neurons.
Disorders resulting from defects in migration of neuronal cells during neurogenesis. Developing nerve cells either fail to migrate or they migrate to incorrect positions resulting in formation of heterotopias, lissencephaly, or other malformations and dysfunctions of the nervous system.
Injury to the nervous system secondary to exposure to lead compounds. Two distinct clinical patterns occur in children (LEAD POISONING, NERVOUS SYSTEM, CHILDHOOD) and adults (LEAD POISONING, NERVOUS SYSTEM, ADULT). In children, lead poisoning typically produces an encephalopathy. In adults, exposure to toxic levels of lead is associated with a peripheral neuropathy.
Neurologic conditions in adults associated with acute or chronic exposure to lead or any of its salts. The most common lead related neurologic syndrome in adults consists of a polyneuropathy involving motor fibers. This tends to affect distal nerves and may present as wrist drop due to RADIAL NEUROPATHY. Additional features of chronic lead exposure include ANEMIA; CONSTIPATION; colicky abdominal pain; a bluish lead line of the gums; interstitial nephritis (NEPHRITIS, INTERSTITIAL); and saturnine gout. An encephalopathy may rarely occur. (From Adams et al., Principles of Neurology, 6th ed, p1212)