Receptores metabotrópicos de glutamato e sua relação com a Esclerose Lateral Amiotrófica (ELA) / Glutamate metabotropic receptors and its relationship with Amiotrophic Lateral Sclerosis (ALS)

A Esclerose Lateral Amiotrófica (ELA), uma doença neurodegenerativa fatal, que afeta neurônios motores superiores e inferiores, tem como fisiopatologia mais aceita a excitotoxicidade mediada por glutamato. O atual estudo tem como objetivo estabelecer a relação entre esse neurotransmissor e a ELA, a partir de uma revisão de literatura nas bases de dados Pubmed e Medline. O glutamato é o principal neurotransmissor do Sistema Nervoso Central (SNC) e a excitotoxicidade gerada pelo seu acúmulo nas fendas sinápticas é tida como um dos principais mecanismos envolvidos na fisiopatologia da ELA. Os indivíduos afetados pela ELA apresentam diminuição da expressão de determinados grupos de receptores metabotrópicos de glutamato (mGlu) nos neurônios e nas células da glia desses pacientes. Os mGlu possuem um papel de destaque na modulação da excitotoxicidade por glutamato e são subdivididos em três grupos. Os mGlus do grupo 1 amplificam as transmissões sinápticas excitatórias rápidas, e os dos grupos 2 e 3 atuam como neuroprotetores inibindo a liberação do glutamato na fenda sináptica. Os mGlus são, portanto, considerados alvos terapêuticos para a atuação de drogas que combatem a excitotoxicidade e induzem a produção de fatores neurotróficos, constituindo importante atuação no combate à ELA.

Amyotrophic Lateral Sclerosis (ALS), a fatal neurodegenerative disease that affects upper and lower motor neurons, has as the most accepted pathophysiology the glutamate-mediated excitotoxicity. The present study aims to establish the relationship between this neurotransmitter and ALS, based on a literature review in the PubMed and Medline databases. Glutamate is the main neurotransmitter of the central nervous system (CNS) and the excitotoxicity generated by its accumulation in the synaptic clefts is considered one of the main mechanisms involved in the pathophysiology of ALS. People affected by ALS present a decrease in expression of certain metabotropic glutamate receptor (mGlu) groups in neurons and glial cells of these patients. mGlu has a prominent role in modulating glutamate excitotoxicity and are subdivided into three groups. Group 1 mGlu amplifies rapid excitatory synaptic transmissions, while groups 2 and 3 act as neuroprotective agents, since among other functions they inhibit glutamate release into the synaptic cleft. Finally, mGlu are considered therapeutic targets for the action of drugs that fight excitotoxicity and induce the production of neurotrophic factors, constituting an important action in the fight against ALS.

Encefalitis autoinmunitaria asociada a anticuerpos contra el receptor N-metil-D-aspartato: presentación de dos casos / Autoimmune encephalitis associated to antibodies against the N-methyl-D-aspartate receptor: Report of two cases

Resumen La encefalitis asociada a anticuerpos contra receptores N-metil-D-aspartato es un síndrome neurológico que se presenta más comúnmente en mujeres jóvenes y frecuentemente se asocia al teratoma de ovario. Se caracteriza por un cuadro clínico agudo con síntomas generales inespecíficos que evoluciona hacia deterioro neurológico, psicosis y convulsiones; en su etapa más avanzada, se asocia con movimientos anormales y disautonomía. Se reportan dos casos en mujeres de 23 y 12 años. Dada su baja incidencia, se explica el proceso clínico que llevó a su diagnóstico y las opciones de tratamiento empleadas.

Abstract Anti-N-methyl-D-aspartate receptor encephalitis is a neurological syndrome that is more common in young women and is often associated with ovarian teratoma. It is characterized by acute general unspecific symptoms that evolve to neurological deterioration, psychosis and seizures. In its more advanced stage it is associated with abnormal movements and dysautonomia. We report two cases in women of 23 and 12 years of age. Given its low incidence, we present the clinical exercise that led to their diagnoses and the treatment options employed.

Ácido domoico e intoxicación amnésica por moluscos en salud pública: [revisión] / Domoic acid and amnesic shellfish poisoning in public health: [review]

El ácido domoico es una biotoxina marina que por primera vez produjo una intoxicación alimentaria en más de cienpersonas en 1987 en Canadá, con muerte en algunos de ellos después de la ingesta de mejillones contaminados. Dentro de las manifestaciones clínicas destacó la amnesia anterógrada, no vista con ninguna biotoxina ni fármaco conocido, pudiendo llegar a ser permanente, por lo cual el síndrome fue denominado intoxicación amnésica por moluscos. En el examen histopatológico del cerebro de los fallecidos, se encontró que el hipocampo fue una de las estructuras más afectadas, con necrosis celular en algunas áreas, lo que explicó el deterioro irreversible de la memoria. Se ha encontrado que muchas especies de mariscos, peces filtradores, krill y animales marinos, pueden contaminarse con dicha biotoxinaque es producida por algunas algas microscópicas y que muchas veces son responsables de las denominadas mareas rojas. La biotoxina puede llegar al humano por la cadena alimenticia. En este artículo, se revisa los brotes tóxicos en mamíferos y aves marinas con posterior muerte debido al ácido domoico, el mecanismo en la producción de toxicidad, su agonismo en los receptores glutamatérgicos, la importancia en la salud pública, sus riesgos por evaluar en la salud humana, así como la difusión de la biotoxina por el mundo, incluyendo el Océano Pacífico y las posibles razones de tal difusión, así como su importancia ecológica y económica que ha obligado a la vigilancia mundial.

Domoic acid is a sea biotoxin that was first identified to produce food poisoning in more than a hundred people inCanada, in 1987, with some deaths reported, after intake of contaminated mussels. As part of the clinical presentation, anterograde amnesia is highlighted. As it had not been seen before with any know biotoxin or drug, and could be permanent, the syndrome was called amnesic poisoning due to shellfish. In the histopathological examination of the brain of the dead patients, the hippocampus was one of the most affected, showing cellular necrosis in some areas, which explains the irreversible deterioration of the memory. Many shellfish species, filtrating fish, krill and marine animalscan get contaminated by the biotoxin , which is produced by microscopic algae, which are often responsible of the redtides. The biotoxin can reach the human being through the food chain. In this article, we revise the toxic outbreaks inmammals and marine birds, causing death due to domoic acid, the mechanism of toxicity production, its agonism in the glutamatergic receptors, its importance in public health, the risk they pose to human health and ought to be evaluated, and the diffusion of the biotoxin throughout the world, including the Pacific Ocean and the possible reasons of this diffusion, as well as its ecologic and economic importance, which has made it surveillance compulsory in all the world.