ABSTRACT
The neural retina is a highly complex tissue composed of excitatory and inhibitory neurons and glial cells. Glutamate, the main excitatory neurotransmitter, mediates information transfer from photoreceptors, bipolar cells, and ganglion cells, whereas interneurons, mainly amacrine and horizontal cells, use γ-aminobutyric acid (GABA), the main inhibitory neurotransmitter. In this review we place an emphasis on glutamate and GABA transporters as highly regulated molecules that play fundamental roles in neurotransmitter clearance, neurotransmitter release, and oxidative stress. We pharmacologically characterized glutamate transporters in chicken retina cells and identified two glutamate transporters: one Na+-dependent transporter and one Na+-independent transporter. The Na+-dependent uptake system presented characteristics related to the high-affinity xAG- system (EAAT1), and the Na+-independent uptake system presented characteristics related to the xCG- system, which highly contributes to glutamate transport in the retina. Glutamate shares the xCG- system with another amino acid, L-cysteine, suggesting the possible involvement of glutathione. Both transporter proteins are present mainly in Müller glial cells. GABA transporters (GATs) mediate high-affinity GABA uptake from the extracellular space and terminate the synaptic action of GABA in the central nervous system. GABA transporters can be modulated by molecules that act on specific sites to promote transporter phosphorylation and dephosphorylation. In addition to a role in the clearance of GABA, GATs may also release GABA through a reverse transport mechanism. In the chicken retina, a GAT-1 blocker, but not GAT2/3 blocker, was shown to inhibit GABA uptake, suggesting that GABA release from retina cells is mainly mediated by a GAT-1-like transporter.
Subject(s)
gamma-Aminobutyric Acid , Glutamic Acid , RetinaABSTRACT
Neurotoxicity induced by methylmercury (MeHg) increases the formation of reactive radicals and accelerates free radical reactions. This review summarizes recent findings in the MeHg-induced formation of free radicals and the role of oxidative stress in its neurotoxicity. Oxidative stress on CNS can produce damage by several interacting mechanisms, including mitochondrial damage with increase in intracellular free Ca(2+), activation and inhibition of enzymes, release of excitatory amino acids, metallothioneins expression, and microtubule disassembly. The nature of antioxidants is discussed and it is suggested that antioxidant enzymes and others antioxidants molecules may protect the central nervous system against neurotoxicity caused by MeHg.
Subject(s)
Animals , Antioxidants/metabolism , Humans , Methylmercury Compounds/toxicity , Nervous System/drug effects , Oxidative StressABSTRACT
Objetivo: realizar um levantamento da literatura existente sobre os níveis de exposição mercurial das populações da região oeste do Estado do Pará. Método: revisão bibliográfica pertinente ao objetivo. Conclusão: os níveis do mercúrio detectados por diferentes trabalhos em populações expostas da bacia do Rio Tapajós foram elevados em certas comunidades (São Luís do Tapajós, Barreiras e Rainha), no entanto, apresentando uma diminuição gradual com o passar dos anos. Esses mesmos dados revelam uma exposição ambiental ao mercúrio de comunidades vizinhas com valores significativos. A exposição mercurial pode ser perigosa, por gerar níveis de intoxicação que estão acima do limite determinado pela Organização Mundial de Saúde, podendo desencadear neurotoxicidade, perda do controle motor entre outros problemas de saúde