Abstract
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 Huntington's disease (HD) and Parkinson'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.
Highlights
Huntington’s disease (HD) and Parkinson’s disease (PD) are distinct neurodegenerative diseases that present with unique motor and cognitive symptoms
We focused on the membrane-associated guanylate kinases (MAGUKs) PSD-95 and SAP97 as they play a major role in regulating glutamate receptor trafficking to synapses and glutamate receptor localisation at synapses [8,9,10, 18, 31]
Quantitative Western blot analysis of hippocampal tissue from control and HD post-mortem human brain tissue revealed that significant changes in synaptic protein levels were occurring with HD
Summary
Huntington’s disease (HD) and Parkinson’s disease (PD) are distinct neurodegenerative diseases that present with unique motor and cognitive symptoms. PD is a sporadic neurodegenerative disease, 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 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 [4,5,6,7]
Sign-in/Register to view highlights & summary Sign-in/Register to access full text options 
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a call
