%0 Journal Article
%T Differential Changes in Postsynaptic Density Proteins in Postmortem HuntingtonĄ¯s Disease and ParkinsonĄ¯s Disease Human Brains
%A C. Fourie
%A E. Kim
%A H. Waldvogel
%A J. M. Wong
%A A. McGregor
%A R. L. M. Faull
%A J. M. Montgomery
%J Journal of Neurodegenerative Diseases
%D 2014
%I Hindawi Publishing Corporation
%R 10.1155/2014/938530
%X NMDA and AMPA-type glutamate receptors and their bound membrane-associated guanylate kinases (MAGUKs) are critical for synapse development and plasticity. We hypothesised that these proteins may play a role in the changes in synapse function that occur in HuntingtonĄ¯s disease (HD) and ParkinsonĄ¯s disease (PD). We performed immunohistochemical analysis of human postmortem brain tissue to examine changes in the expression of SAP97, PSD-95, GluA2 and GluN1 in human control, and HD- and PD-affected hippocampus and striatum. Significant increases in SAP97 and PSD-95 were observed in the HD and PD hippocampus, and PSD95 was downregulated in HD striatum. We observed a significant increase in GluN1 in the HD hippocampus and a decrease in GluA2 in HD and PD striatum. Parallel immunohistochemistry experiments in the YAC128 mouse model of HD showed no change in the expression levels of these synaptic proteins. Our human data show that major but different changes occur in glutamatergic proteins in HD versus PD human brains. Moreover, the changes in human HD brains differ from those occurring in the YAC128 HD mouse model, suggesting that unique changes occur at a subcellular level in the HD human hippocampus. 1. Introduction HuntingtonĄ¯s disease (HD) and ParkinsonĄ¯s disease (PD) are distinct neurodegenerative diseases that present with unique motor and cognitive symptoms. HD is an autosomal dominant inherited disease caused by the expansion of a polyglutamine repeat sequence in the huntingtin gene, which results in a progressive loss of medium spiny neurons in the striatum [1]. PD is a sporadic neurodegenerative disease, although there are rare familial cases. It is marked by the loss of dopaminergic neurons of the substantia nigra pars compacta, which leads to abnormal basal ganglia circuitry, resulting in motor symptoms [2, 3]. Treatments for these diseases are symptomatic and new therapeutic targets are of the essence. Emphasis is now being placed on the changes that occur at the synapse and the processes that underlie cognitive dysfunction as it has been shown that synaptic and cognitive dysfunction occurs long before the onset of clinical symptoms in the human [4¨C7]. Glutamate receptors are currently viewed as valuable therapeutic targets in both HD [6] and PD [7]. N-Methyl-D-Aspartate (NMDA) and alpha-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA)-type glutamate receptors and their bound postsynaptic density-membrane associated guanylate kinases (PSD-MAGUKs) are critical for synapse development and plasticity [8¨C12]. MAGUKs act as scaffolding
%U http://www.hindawi.com/journals/jnd/2014/938530/