Can we predict who is at risk of facing cognitive issues in PD and address them earlier? These are the questions being pursued by Dr. Goldman of the PDF Research Center at Rush University Medical Center.
PDF Grant Programs
Are you interested in furthering Parkinson's science? View PDF's open grant programs.
Increased vesicular monoamine transporter enhances dopamine release and opposes Parkinson disease-related neurodegeneration in vivo.
PDF's targeted PubMed search provides you with access to journal articles from the last 90 days that may be pertinent to Parkinson's disease research.
Not what you're looking for? Do you need informational publications about Parkinson's targeted for people living with Parkinson's, caregivers and family members? Please browse PDF's educational materials and programs - which are all available electronically or in print. Order for yourself, a loved one or in bulk for your patients or support group.
Proc Natl Acad Sci U S A 2014 Jul; 111(27):9977-82
Authors: Kelly M Lohr, Alison I Bernstein, Kristen A Stout, Amy R Dunn, Carlos R Lazo, Shawn P Alter, Minzheng Wang, Yingjie Li, Xueliang Fan, Ellen J Hess, Hong Yi, Laura M Vecchio, David S Goldstein, Thomas S Guillot, Ali Salahpour, Gary W Miller
Disruption of neurotransmitter vesicle dynamics (transport, capacity, release) has been implicated in a variety of neurodegenerative and neuropsychiatric conditions. Here, we report a novel mouse model of enhanced vesicular function via bacterial artificial chromosome (BAC)-mediated overexpression of the vesicular monoamine transporter 2 (VMAT2; Slc18a2). A twofold increase in vesicular transport enhances the vesicular capacity for dopamine (56%), dopamine vesicle volume (33%), and basal tissue dopamine levels (21%) in the mouse striatum. The elevated vesicular capacity leads to an increase in stimulated dopamine release (84%) and extracellular dopamine levels (44%). VMAT2-overexpressing mice show improved outcomes on anxiety and depressive-like behaviors and increased basal locomotor activity (41%). Finally, these mice exhibit significant protection from neurotoxic insult by the dopaminergic toxicant 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP), as measured by reduced dopamine terminal damage and substantia nigra pars compacta cell loss. The increased release of dopamine and neuroprotection from MPTP toxicity in the VMAT2-overexpressing mice suggest that interventions aimed at enhancing vesicular capacity may be of therapeutic benefit in Parkinson disease.
PMID: 24979780 [PubMed - as supplied by publisher]