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Selective neuronal death following exposure to methylenedioxypyrovalerone is accompanied by an inhibition of NMDA receptor NR2B subunit expression

AuthorsGerecsei, László István; Balázsa, Tamás; Echevarría, Diego; Ádám, Ágota; Zachar, Gergely; Csillag, András
Basal ganglia
Nucleus accumbens
Issue Date2019
PublisherMinistry of Science and Higher Education (Poland)
CitationActa Neurobiologiae Experimentalis 79(1): 92-100 (2019)
AbstractIn a previous study, methylenedioxypyrovalerone (MDPV), a designer drug of the cathinone family, caused selective enhancement of Caspase3 immunoreactive (Casp3+) apoptotic cells in the nucleus accumbens (NAc) of 7‑day‑old mice. To further elaborate on the mechanism underlying MDPV‑elicited apoptosis, here, we investigated the appearance of Casp3+ cells in developing neural tube explants of E12.5 mice, following MDPV treatment in vitro. Apoptotic cells appeared in large number in the pallium as radial progenitor cells and multipolar neurons, and in the subpallium including the future NAc, both in control and MDPV treated specimens. MDPV did not cause gross morphological changes in the neural tube or in the abundance of Casp3+ cells, based on a visual impression, though quantification was not attempted. We also studied the changes in NMDA receptor (NMDAR) protein subunits NR1 and NR2B in the NAc of 7‑day‑old MDPV treated and control mice, using western blotting of tissue obtained by selective dissection. In MDPV treated animals, expression of NR2B was lower than in the control animals, whereas expression of NR1 did not differ significantly from controls. The findings indicate that, during early postembryonic development, downregulation of the NR2B receptor subunit (at this time predominant in the NMDAR) is accompanied by a decreased viability of neurons. Decreased viability is expressed, in this case, as enhanced susceptibility to stimulation by MDPV - essentially a robust dopaminergic agent, potently affecting the neurons of the NAc. The findings are likely relevant to dopaminergic/NMDAR interactions and a potential pro‑survival role of the NR2B subunit in critical phases of neural development.
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