Assessment of the Protection of Dopaminergic Neurons by an α7 Nicotinic Receptor Agonist, PHA 543613 Using [18F]LBT-999 in a Parkinson’s Disease Rat Model
Sophie Sérrière, Aurélie Doméné, Johnny Vercouillie, Céline Mothes, Sylvie Bodard, Nuno Rodrigues, Denis Guilloteau, Sylvain Routier, Guylène Page, Sylvie Chalon
Abstract
The inverse association between nicotine intake and Parkinson's disease (PD) is well established and suggests that this molecule could be neuroprotective through anti-inflammatory action mediated by nicotinic receptors, including the α7-subtype (α7R). The objective of this study was to evaluate the effects of an agonist of α7R, PHA 543613, on striatal dopaminergic neurodegeneration and neuroinflammation in a rat model of PD induced by 6-hydroxydopamine (6-OHDA) lesion. Adult male Wistar rats were lesioned in the right striatum and assigned to either the PHA group (n = 7) or the Sham group (n = 5). PHA 543613 hydrochloride at the concentration of 6 mg/kg (PHA group) or vehicle (Sham group) was intra-peritoneally injected 2 h before 6-OHDA lesioning and then at days 2, 4, and 6 post-lesion. Positron emission tomography (PET) imaging was performed at 7 days post-lesion using [(18)F]LBT-999 to quantify the striatal dopamine transporter (DAT). After PET imaging, neuroinflammation was evaluated in same animals in vitro through the measurement of the microglial activation marker 18 kDa translocator protein (TSPO) by quantitative autoradiography with [(3)H]PK-11195. The DAT density reflecting the integrity of dopaminergic neurons was significantly decreased while the intensity of neuroinflammation measured by TSPO density was significantly increased in the lesioned compared to intact striatum in both groups. However, these both modifications were partially reversed in the PHA group compared to Sham. In addition, a significant positive correlation between the degree of lesion and the intensity of neuroinflammation was evidenced. These findings indicate that PHA 543613 exerts neuroprotective effects on the striatal dopaminergic neurons associated with a reduction in microglial activation in this model of PD. This reinforces the hypothesis that an α7R agonist could provide beneficial effects for the treatment of PD.
Pharmacology, Toxicology and Pharmaceutical Science
3
16%
Environmental Science
3
16%
Agricultural and Biological Sciences
2
11%
Economics, Econometrics and Finance
1
5%
Other
3
16%
Unknown
3
16%
Attention Score in Context
Attention Score in Context
This research output has an Altmetric Attention Score of 5. This is our high-level measure of the quality and quantity of online attention that it has received. This Attention Score, as well as the ranking and number of research outputs shown below, was calculated when the research output was last mentioned on 22 August 2021.
All research outputs
#6,291,333
of 22,829,083 outputs
Outputs from Frontiers in Medicine
#1,369
of 5,652 outputs
Outputs of similar age
#73,978
of 267,078 outputs
Outputs of similar age from Frontiers in Medicine
#5
of 15 outputs
Altmetric has tracked 22,829,083 research outputs across all sources so far. This one has received more attention than most of these and is in the 72nd percentile.
So far Altmetric has tracked 5,652 research outputs from this source. They typically receive a lot more attention than average, with a mean Attention Score of 13.0. This one has done well, scoring higher than 75% of its peers.
Older research outputs will score higher simply because they've had more time to accumulate mentions. To account for age we can compare this Altmetric Attention Score to the 267,078 tracked outputs that were published within six weeks on either side of this one in any source. This one has gotten more attention than average, scoring higher than 71% of its contemporaries.
We're also able to compare this research output to 15 others from the same source and published within six weeks on either side of this one. This one has gotten more attention than average, scoring higher than 66% of its contemporaries.
