Interrogating the aged striatum: robust survival of grafted dopamine neurons in aging rats produces inferior behavioral recovery and evidence of impaired integration

Neurobiology of Disease
Timothy J CollierKathy Steece-Collier

Abstract

Advanced age is the primary risk factor for Parkinson's disease (PD). In PD patients and rodent models of PD, advanced age is associated with inferior symptomatic benefit following intrastriatal grafting of embryonic dopamine (DA) neurons, a pattern believed to result from decreased survival and reinnervation provided by grafted neurons in the aged host. To help understand the capacity of the aged, parkinsonian striatum to be remodeled with new DA terminals, we used a grafting model and examined whether increasing the number of grafted DA neurons in aged rats would translate to enhanced behavioral recovery. Young (3months), middle-aged (15months), and aged (22months) parkinsonian rats were grafted with proportionately increasing numbers of embryonic ventral mesencephalic (VM) cells to evaluate whether the limitations of the graft environment in subjects of advancing age can be offset by increased numbers of transplanted neurons. Despite robust survival of grafted neurons in aged rats, reinnervation of striatal neurons remained inferior and amelioration of levodopa-induced dyskinesias (LID) was delayed or absent. This study demonstrates that: 1) counter to previous evidence, under certain conditions the aged striatum can support...Continue Reading

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Citations

Feb 18, 2016·Parkinson's Disease·Elisabetta TronciManolo Carta
Mar 31, 2016·Neuroscience and Biobehavioral Reviews·Tetsuya AsakawaYing Xia
Oct 28, 2015·The Journals of Gerontology. Series A, Biological Sciences and Medical Sciences·Ana MuñozJose L Labandeira-Garcia
Apr 15, 2016·Stem Cells Translational Medicine·Jannette Rodriguez-PallaresJose L Labandeira-Garcia
May 19, 2017·Movement Disorders : Official Journal of the Movement Disorder Society·Timothy J CollierJeffrey H Kordower
Apr 20, 2019·Movement Disorders : Official Journal of the Movement Disorder Society·Kathy Steece-CollierFredric P Manfredsson
Jun 25, 2019·Movement Disorders : Official Journal of the Movement Disorder Society·Timothy J CollierKathy Steece-Collier
Mar 1, 2019·Rinshō shinkeigaku = Clinical neurology·Asuka Morizane
Dec 27, 2019·Neuroscience and Biobehavioral Reviews·Mujun SunSandy R Shultz

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