Neuroscience, 17 December 2015, Vol.311, pp.539-551
Parkinson’s disease (PD) is a well-characterized neurological disorder with regard to its neuropathological and symptomatic appearance. At the genetic level, mutations of particular genes, e.g. and , were found in human hereditary PD with early onset. Neurotransmitter receptors constitute decisive elements in neural signal transduction. Furthermore, since they are often altered in neurological and psychiatric diseases, receptors have been successful targets for pharmacological agents. However, the consequences of PD-associated gene mutations on the expression of transmitter receptors are largely unknown. Therefore, we studied the expression of 16 different receptor binding sites of the neurotransmitters glutamate, GABA, acetylcholine, adrenaline, serotonin, dopamine and adenosine by means of quantitative receptor autoradiography in and knockout mice. These knockout mice exhibit electrophysiological and behavioral deficits, but do not show the typical dopaminergic cell loss. We demonstrated differential changes of binding site densities in eleven brain regions. Most prominently, we found an up-regulation of GABA and kainate receptor densities in numerous cortical areas of and knockout mice, as well as increased NMDA but decreased AMPA receptor densities in different brain regions of the knockout mice. The alterations of three different glutamate receptor types may indicate the potential relevance of the glutamatergic system in the pathogenesis of PD. Furthermore, the cholinergic M , M and nicotinic receptors as well as the adrenergic α and the adenosine A receptors showed differentially increased densities in and knockout mice. Taken together, knockout of the PD-associated genes or results in differential changes of neurotransmitter receptor densities, highlighting a possible role of altered non-dopaminergic, and in particular of glutamatergic neurotransmission in PD pathogenesis.
Parkinson’s Disease ; Neurotransmitter Receptor ; Parkin ; Dj-1 ; Knockout Mouse ; Anatomy & Physiology
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