Stuckenholz et al. (2013). Journal of Parkinson s Disease. doi: 10.3233/jpd-120157
…ine hydroxylase (TH) (rabbit anti-TH; 1: 1000; Pel-Freez Biologicals, Rogers, USA) on day seven after MPTP intoxication (d7). At that time, the number of TH+ cells correlates with the number of Nissl-stained neuronal cells. Seven days post injection, the count of TH+ cells is even more spe- cific and convenient that counting Nissl-stained cells [18]. A biotinylated goat anti-rabbit antibody (1:2
Abstract
Background: Parkinson's disease (PD) is associated with neurodegeneration of dopaminergic neurons and an accompanying neuroinflammatory process in the substantia nigra (SN). The cholinergic anti-inflammatory signalling pathway allows the autonomic nervous system to modulate immunologic stimuli and inflammatory processes. A major component of this pathway is the α7 nicotinic acetylcholine receptor (α7 nACh receptor), which is expressed on immune cells such as microglia. Objective: To determine the role of this cholinergic anti-inflammatory signalling pathway, we investigated the effects of the selective α7 nACh agonist PNU-282987 and of the non-competitive nACh antagonist mecamylamine on microglia-induced neuroinflammation and toxin-induced degeneration of dopaminergic neurons in a mouse model of PD. Methods: PNU-282987, mecamylamine or placebo administration was started one day before MPTP intoxication and repeated daily until sacrifice after MPTP intoxication. C57Bl/6 mice were injected intraperitoneally four times at 2 h intervals with either 20 mg/kg MPTP-HCl or a corresponding volume of saline. Two or seven days after the end of the MPTP intoxication, the animals were killed and their brains were processed for further analysis. Results: Treatment with PNU-282987 resulted in an attenuation of neuroinflammation in the MPTP-lesioned SN. Furthermore, PNU-282987 attenuated MPTP-induced dopaminergic cell loss in the SN and reduced striatal dopamine depletion. Unexpectedly, mecamylamine lowered neuroinflammation as well, though it did not show a neuroprotective potential at the nigral level. Conclusions: Our results demonstrate the therapeutic potential of the selective α7 nicotinic acetylcholine agonist PNU-282987 in attenuating neuroinflammation and toxin-induced loss of dopaminergic neurons in the acute MPTP mouse model of PD.