RT Journal Article
T1 Cadmium induced ROS alters M1 and M3 receptors, leading to SN56 cholinergic neuronal loss, through AChE variants disruption
A1 Moyano-Cires Ivanoff, Paula Viviana
A1 De Frias, Mariano
A1 Lobo Alonso, Margarita
A1 Anadón Baselga, María José
A1 Sola Vendrell, Emma
A1 Pelayo Alarcón, Adela
A1 Díaz Plaza, María Jesús
A1 Frejo Moya, María Teresa
A1 Pino Sans, Javier Del
AB Cadmium, an environmental neurotoxic compound, produces cognitive disorders, although the mechanism remains unknown. Previously, we described that cadmium induces a more pronounced cell death on cholinergic neurons from basal forebrain (BF). This effect, partially mediated by M1 receptor blockade, triggering it through AChE splices variants alteration, may explain cadmium effects on learning and memory processes. Cadmium has been also reported to induce oxidative stress generation leading to M2 and M4 muscarinic receptors alteration, in hippocampus and frontal cortex, which are necessary to maintain cell viability and cognitive regulation, so their alteration in BF could also mediate this effect. Moreover, it has been reported that antioxidant treatment could reverse cognitive disorders, muscarinic receptor and AChE variants alterations induced by cadmium. Thus, we hypothesized that cadmium induced cell death of BF cholinergic neurons is mediated by oxidative stress generation and this mechanism could produce this effect, in part, through AChE variants altered by muscarinic receptors disruption. To prove this, we evaluated in BF SN56 cholinergic neurons, whether cadmium induces oxidative stress and alters muscarinic receptors, and their involvement in the induction of cell death through alteration of AChE variants. Our results show that cadmium induces oxidative stress, which mediates partially the alteration of AChE variants and M2 to M4 muscarinic receptors expression and blockage of M1 receptor. In addition, cadmium induced oxidative stress generation by M1 and M3 receptors alteration through AChE variants disruption, leading to cell death. These results provide new understanding of the mechanisms contributing to cadmium harmful effects on cholinergic neurons.
PB Elsevier
SN 0893-228X
YR 2018
FD 2018
LK https://hdl.handle.net/20.500.14352/100485
UL https://hdl.handle.net/20.500.14352/100485
LA eng
NO Cadmium induced ROS alters M1 and M3 receptors, leading to SN56 cholinergic neuronal loss, through AChE variants disruption. Moyano P, de Frias M, Lobo M, Anadon MJ, Sola E, Pelayo A, Diaz MJ, Frejo MT, Del Pino J. Toxicology. 2018 Feb 1; 394: 54-62
NO Banco Santander
NO Universidad Complutense de Madrid
DS Docta Complutense
RD 9 abr 2025