PMID- 23006318 OWN - NLM STAT- MEDLINE DCOM- 20130703 LR - 20130123 IS - 1601-183X (Electronic) IS - 1601-183X (Linking) VI - 12 IP - 1 DP - 2013 Feb TI - Relationship between BDNF expression in major striatal afferents, striatum morphology and motor behavior in the R6/2 mouse model of Huntington's disease. PG - 108-24 LID - 10.1111/j.1601-183X.2012.00858.x [doi] AB - Patients with Huntington's disease (HD) and transgenic mouse models of HD show neuronal loss in the striatum as a major feature, which contributes to cognitive and motor manifestations. Reduced expression of the neurotrophin brain-derived neurotrophic factor (BDNF) in striatal afferents may play a role in neuronal loss. How progressive loss of BDNF expression in different cortical or subcortical afferents contributes to striatal atrophy and behavioral dysfunction in HD is not known, and may best be determined in animal models. We compared age-dependent alterations of BDNF mRNA expression in major striatal afferents from the cerebral cortex, thalamus and midbrain in the R6/2 transgenic mouse model of HD. Corresponding changes in striatal morphology were quantified using unbiased stereology. Changes in motor behavior were measured using an open field, grip strength monitor, limb clasping and a rotarod apparatus. BDNF expression in cortical limbic and midbrain striatal afferents is reduced by age 4 weeks, prior to onset of motor abnormalities. BDNF expression in motor cortex and thalamic afferents is reduced by 6 weeks, coinciding with early motor dysfunction and reduced striatum volume. BDNF loss in afferents progresses until death at 13-15 weeks, correlating with progressive striatal neuronal loss and motor abnormalities. Mutant huntingtin protein expression in R6/2 mice results in progressive loss of BDNF in both cortical and subcortical striatal afferents. BDNF loss in limbic and dopaminergic striatal inputs may contribute to cognitive/psychiatric dysfunction in HD. Subsequent BDNF loss in cortical motor and thalamic afferents may accelerate striatal degeneration, resulting in progressive involuntary movements. CI - (c) 2012 The Authors. Genes, Brain and Behavior (c) 2012 Blackwell Publishing Ltd and International Behavioural and Neural Genetics Society. FAU - Samadi, P AU - Samadi P AD - Cone Laboratory, Montreal Neurological Institute, Department of Neurology and Neurosurgery, McGill University, Montreal, Quebec, Canada. FAU - Boutet, A AU - Boutet A FAU - Rymar, V V AU - Rymar VV FAU - Rawal, K AU - Rawal K FAU - Maheux, J AU - Maheux J FAU - Kvann, J-C AU - Kvann JC FAU - Tomaszewski, M AU - Tomaszewski M FAU - Beaubien, F AU - Beaubien F FAU - Cloutier, J F AU - Cloutier JF FAU - Levesque, D AU - Levesque D FAU - Sadikot, A F AU - Sadikot AF LA - eng GR - Canadian Institutes of Health Research/Canada PT - Journal Article PT - Research Support, Non-U.S. Gov't DEP - 20121121 PL - England TA - Genes Brain Behav JT - Genes, brain, and behavior JID - 101129617 RN - 0 (Brain-Derived Neurotrophic Factor) RN - 0 (RNA, Messenger) SB - IM MH - Afferent Pathways/metabolism/physiopathology MH - Age Factors MH - Animals MH - Brain-Derived Neurotrophic Factor/genetics/*metabolism MH - Cerebral Cortex/metabolism/*physiopathology MH - Disease Models, Animal MH - Gene Expression MH - Hand Strength MH - Huntington Disease/*metabolism/pathology/physiopathology MH - Mice MH - Mice, Inbred C57BL MH - Mice, Inbred CBA MH - *Motor Activity MH - Mutation MH - Neostriatum/metabolism/*pathology/physiopathology MH - RNA, Messenger/metabolism MH - Thalamus/metabolism/*physiopathology EDAT- 2012/09/26 06:00 MHDA- 2013/07/05 06:00 CRDT- 2012/09/26 06:00 PHST- 2012/05/02 00:00 [received] PHST- 2012/08/08 00:00 [revised] PHST- 2012/09/13 00:00 [revised] PHST- 2012/09/17 00:00 [accepted] PHST- 2012/09/26 06:00 [entrez] PHST- 2012/09/26 06:00 [pubmed] PHST- 2013/07/05 06:00 [medline] AID - 10.1111/j.1601-183X.2012.00858.x [doi] PST - ppublish SO - Genes Brain Behav. 2013 Feb;12(1):108-24. doi: 10.1111/j.1601-183X.2012.00858.x. Epub 2012 Nov 21.