Publication: Efectos neurotóxicos del cadmio sobre el sistema colinérgico a nivel del sistema nervioso central de la rata y su implicación en el desarrollo de enfermedades neurodegenerativas
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2021-07-19
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Universidad Complutense de Madrid
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Abstract
El cadmio (Cd) es uno de los principales agentes tóxicos asociado a contaminación ambiental e industrial, que ocasiona el hombre un elevado número de intoxicaciones al año, produciendo efectos tóxicos en distintos órganos (ATSDR, 2012). A nivel del sistema nervioso central (SNC) produce alteraciones neuropatológicas y neuroquímicas que pueden conducir a una disfunción cognitiva de la que no se conocen, hasta el momento, los mecanismos implicados (Chin-Chan et al., 2015). Se sabe que los procesos de aprendizaje y memoria son regulados por el sistema colinérgico del prosencéfalo basal (PSB), por lo que el bloqueo de la transmisión colinérgica o muerte de neuronas colinérgicas a dicho nivel podría estar relacionado con el deterioro de memoria inducido por el Cd, como se ha observado en enfermedades neurodegenerativas como la enfermedad de Alzheimer (EA). En este sentido se ha descrito que el Cd, además de alterar la transmisión colinérgica, induce una muerte neuronal no selectiva pero más pronunciada en cultivos de neuronas colinérgicas SN56 procedentes del PSB (Del Pino et al., 2014). Estas alteraciones están mediadas, en parte, por la inducción de especies reactivas de oxigeno (ERO) y por el bloqueo del receptor muscarínico M1 (MR1) (Del Pino et al., 2018), que a su vez desencadenan una alteración de las variantes de la acetilcolinesterasa (AChE), las cuales inducen la sobreexpresión de la enzima glucógeno sintetasa quinasa 3 (GSK-3 β) y el aumento de proteínas beta amiloideas (Aβ), Tau totales y fosforiladas (Del Pino et al., 2016a; Del Pino et al., 2016b). Por lo tanto, la reproducción de estos mecanismos in vivo podría confirmar su participación en las alteraciones cognitivas descritas...
Cadmium (Cd) is one of the main toxic agents associated with environmental and industrial pollution, that causes a large number of intoxications in humans every year, producing toxic effects in several organs (ATSDR, 2012). Cd produces neuropathological and neurochemical alterations, leading to cognitive dysfunction in central nervous system (Chin-Chan et al., 2015). However, the mechanisms involved are unknown. Learning and memory processes are regulated by the cholinergic system of the basal forebrain (BF), so the blocking of the cholinergic transmission or the induction of cell death in BF cholinergic neurons could be related to the memory deterioration observed after cadmium exposure. These dysfunctions have been observed in neurodegenerative diseases such as Alzheimer’s disease. In this regard, cadmium has been described to alter cholinergic transmission and induce a non-selective neurological cell death that is more pronounced in primary cholinergic neuron from BF (Del Pino et al., 2014). These alterations are partly produced by the induction of reactive oxygen species and by the blocking of muscarinic receptors M1, which trigger a modification in the acetylcholinesterase (AChE) variants expression (Del Pino et al., 2018). These alterations lead to the over-expression of the glycogen synthase kinase 3 beta (GSK-3b) and the increase of beta amyloid (Ab), total and phosphorylated Tau proteins (Del Pino et al., 2016a; Del Pino et al., 2016b). Therefore, the reproductions of these mechanisms in vivo could confirm their participation in the cognitive modifications described...
Cadmium (Cd) is one of the main toxic agents associated with environmental and industrial pollution, that causes a large number of intoxications in humans every year, producing toxic effects in several organs (ATSDR, 2012). Cd produces neuropathological and neurochemical alterations, leading to cognitive dysfunction in central nervous system (Chin-Chan et al., 2015). However, the mechanisms involved are unknown. Learning and memory processes are regulated by the cholinergic system of the basal forebrain (BF), so the blocking of the cholinergic transmission or the induction of cell death in BF cholinergic neurons could be related to the memory deterioration observed after cadmium exposure. These dysfunctions have been observed in neurodegenerative diseases such as Alzheimer’s disease. In this regard, cadmium has been described to alter cholinergic transmission and induce a non-selective neurological cell death that is more pronounced in primary cholinergic neuron from BF (Del Pino et al., 2014). These alterations are partly produced by the induction of reactive oxygen species and by the blocking of muscarinic receptors M1, which trigger a modification in the acetylcholinesterase (AChE) variants expression (Del Pino et al., 2018). These alterations lead to the over-expression of the glycogen synthase kinase 3 beta (GSK-3b) and the increase of beta amyloid (Ab), total and phosphorylated Tau proteins (Del Pino et al., 2016a; Del Pino et al., 2016b). Therefore, the reproductions of these mechanisms in vivo could confirm their participation in the cognitive modifications described...
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Tesis inédita de la Universidad Complutense de Madrid, Facultad de Medicina, Departamento de Toxicología y Legislación Sanitaria, leída el 27/01/2021