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. 2018 Dec 10;12:479. doi: 10.3389/fncel.2018.00479

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Copyright © 2018 Sancandi, Schul, Economides, Constanti and Mercer.

This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.

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Distribution of calcium-binding proteins (CBPs) in the model of pre-motor PD. (A) Neuroprotective effect of EX-4 on parvalbumin (PV)-immunopositive interneurons in the PC of the pre-motor model. (Aa) Example of PV-immunostaining in the anterior PC of sham animals, model and model + EX-4 treatment at 19 days after surgery. (Ab) Cell densities in the PC of all experimental groups at 19 days after surgery expressed as the number of PV-positive neurones per mm³. The number of PV-positive interneurons was significantly decreased in the pre-motor model compared with that in the sham animals. Treatment with EX-4 prevented this decrease. The distribution of PV-positive neurones following treatment with EX-4 and EX9-39 was similar to that in sham animals. (B) Neuroprotective effect of EX-4 on calbindin (CB)-immunopositive interneurons in the PC of the pre-motor model. (Ba) Example of CB-immunostaining in the anterior PC of sham animals and model with and without EX-4 treatment at 19 days after surgery. (Bb) Cell densities in the PC of all experimental groups at 19 days after surgery expressed as the number of CB-positive neurones per mm³. A large decrease in the number of CB-positive interneurons was observed in the pre-motor model compared with the sham animals. Treatment with EX-4 prevented this decrease following activation of GLP-1Rs as the distribution of CB-positive neurones was similar to that in the pre-motor model. (C) Distribution of calretinin (CR)-immunopositive interneurons in the PC of the pre-motor model. (Ca) Example of CR-immunostaining in the anterior PC of sham animals and model with and without EX-4 treatment at 19 days after surgery. (Cb) Cell densities in the PC of all experimental groups at 19 days after surgery expressed as the number of CR-positive neurones per mm³. A decrease in the number of CR-positive interneurons was observed in pre-motor model compared with the sham animals. Treatment with EX-4 prevented this decrease. The distribution of CR-positive neurones following treatment with EX-4 and EX9-39 was similar to that in the sham animals and pre-motor model treated with EX-4 only (Kruskal–Wallis test ^∗P < 0.05, ^∗∗P < 0.01, ^∗∗∗P < 0.001, ^∗∗∗∗P < 0.0001).