Changes in the expression of neurotransmitter receptors in Parkin and DJ-1 knockout mice – A quantitative multireceptor study

Cremer, Jennifer; Schleicher, Axel; Piel, M.; Amunts, K.; Zilles, K.; Rösch, F.; Palomero-Gallagher, N.

doi:10.1016/j.neuroscience.2015.10.054

Typ	Amount	VAT	Currency	Share	Status	Cost centre
Colour charges	590.00	0.00	EUR	100.00 %	(Zahlung erfolgt)	ZB
Sum	590.00	0.00	EUR
Total	590.00

Journal Article

FZJ-2015-06844

Changes in the expression of neurotransmitter receptors in Parkin and DJ-1 knockout mice – A quantitative multireceptor study

Cremer, J. (Corresponding author)FZJ* ; Amunts, K.FZJ* ; Schleicher, A. ; Palomero-Gallagher, N.FZJ* ; Piel, M. ; Rösch, F. ; Zilles, K.FZJ*

2015
Elsevier Science Amsterdam [u.a.]

Neuroscience 311, 539 - 551 (2015) [10.1016/j.neuroscience.2015.10.054]

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Please use a persistent id in citations: doi:10.1016/j.neuroscience.2015.10.054

Abstract: 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. Parkin and DJ-1, 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 Parkin and DJ-1 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 GABAB and kainate receptor densities in numerous cortical areas of Parkin and DJ-1 knockout mice, as well as increased NMDA but decreased AMPA receptor densities in different brain regions of the Parkin 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 M1, M2 and nicotinic receptors as well as the adrenergic α2 and the adenosine A2A receptors showed differentially increased densities in Parkin and DJ-1 knockout mice.Taken together, knockout of the PD-associated genes Parkin or DJ-1 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.

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