title: Hippocampal neurogenesis, cognitive deficits and affective disorder in Huntington's disease.
abstract: Huntington's disease (HD) is a neurodegenerative disorder caused by a tandem repeat expansion encoding a polyglutamine tract in the huntingtin protein. HD involves progressive psychiatric, cognitive, and motor symptoms, the selective pathogenesis of which remains to be mechanistically elucidated. There are a range of different brain regions, including the cerebral cortex and striatum, known to be affected in HD, with evidence for hippocampal dysfunction accumulating in recent years. In this review we will focus on hippocampal abnormalities, in particular, deficits of adult neurogenesis. We will discuss potential molecular mechanisms mediating disrupted hippocampal neurogenesis, and how this deficit of cellular plasticity may in turn contribute to specific cognitive and affective symptoms that are prominent in HD. The generation of transgenic animal models of HD has greatly facilitated our understanding of disease mechanisms at molecular, cellular, and systems levels. Transgenic HD mice have been found to show progressive behavioral changes, including affective, cognitive, and motor abnormalities. The discovery, in multiple transgenic lines of HD mice, that adult hippocampal neurogenesis and synaptic plasticity is disrupted, may help explain specific aspects of cognitive and affective dysfunction. Furthermore, these mouse models have provided insight into potential molecular mediators of adult neurogenesis deficits, such as disrupted serotonergic and neurotrophin signaling. Finally, a number of environmental and pharmacological interventions which are known to enhance adult hippocampal neurogenesis have been found to have beneficial affective and cognitive effects in mouse models, suggesting common molecular targets which may have therapeutic utility for HD and related diseases.
authors: Florey Neuroscience Institutes, Melbourne Brain Centre, University of Melbourne, Melbourne, VIC 3010, Australia.
authors: Mark I
authors: MI
authors: Ransome
authors: Thibault
authors: T
authors: Renoir
authors: Anthony J
authors: AJ
authors: Hannan
mesh_terms: D000818:Animals; D003072:Cognition Disorders / Q000209:etiology / Q000473:pathology* / Q000523:psychology; D004195:Disease Models, Animal; D006624:Hippocampus / Q000254:growth & development* / Q000473:pathology*; D006801:Humans; D006816:Huntington Disease / Q000150:complications / Q000473:pathology* / Q000523:psychology; D051379:Mice; D008822:Mice, Transgenic; D019964:Mood Disorders / Q000209:etiology / Q000473:pathology* / Q000523:psychology; D055495:Neurogenesis / Q000502:physiology*; D009473:Neuronal Plasticity / Q000502:physiology