Glutamate receptors in the mammalian central nervous system

Ozawa, Seiji; Kamiya, Haruyuki; Tsuzuki, Keisuke

doi:10.1016/s0301-0082(97)00085-3

Cited by 972 publications

(670 citation statements)

References 388 publications

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“…Although these AAs are primarily involved in intermediary metabolism and other non-neuronal functions, their most important role is as neurotransmitters. It is estimated Glu mediates nearly 50% of all the synaptic transmissions in the CNS and its involvement is implicated in nearly all aspects of normal brain function including learning, memory, movement, cognition and development 21,[26][27][28][29][30][31][32][33][34] .…”

Section: Excitatory Amino Acids (Eaas)mentioning

confidence: 99%

A Review of Glutamate Receptors I: Current Understanding of Their Biology

Rousseaux

2008

J Toxicol Pathol

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Seventy years ago it was discovered that glutamate is abundant in the brain and that it plays a central role in brain metabolism. However, it took the scientific community a long time to realize that glutamate also acts as a neurotransmitter. Glutamate is an amino acid and brain tissue contains as much as 5 -15 mM glutamate per kg depending on the region, which is more than of any other amino acid. The main motivation for the ongoing research on glutamate is due to the role of glutamate in the signal transduction in the nervous systems of apparently all complex living organisms, including man. Glutamate is considered to be the major mediator of excitatory signals in the mammalian central nervous system and is involved in most aspects of normal brain function including cognition, memory and learning. In this review, the basic biology of the excitatory amino acids glutamate, glutamate receptors, GABA, and glycine will first be explored. In the second part of this review, the known pathophysiology and pathology will be described. (J Toxicol Pathol 2008; 21: 25-51)

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Section: Excitatory Amino Acids (Eaas)mentioning

confidence: 99%

A Review of Glutamate Receptors I: Current Understanding of Their Biology

Rousseaux

2008

J Toxicol Pathol

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“…Glutamate is the major excitatory neurotransmitter in the central nervous system, including the retina (Ozawa et al, 1998). Photoreceptors, bipolar cells and ganglion cells release glutamate to mediate the transfer of visual signals from the retina to the brain.…”

Section: Introductionmentioning

confidence: 99%

Diabetes changes ionotropic glutamate receptor subunit expression level in the human retina

et al. 2008

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Early diabetic retinopathy is characterized by changes in subtle visual functions such as contrast sensitivity and dark adaptation. The outcome of several studies suggests that glutamate is involved in retinal neurodegeneration during diabetes. We hypothesized that the protein levels of ionotropic glutamate receptor subunits are altered in the retina during diabetes. Therefore, we investigated whether human diabetic patients have altered immunoreactivity of ionotropic glutamate receptor subunits in the retina. In total, 12 donor eyes from subjects with diabetes mellitus were examined and compared to 6 eyes from non-diabetic subjects without known ocular disease, serving as controls. Immunohistochemical analysis was performed using specific antibodies directed against the ionotropic α-amino-3-hydroxy-5-methyl-isoxazole-4-propionate (AMPA) receptor subunits GluR1, GluR2, GluR4, and against the N-methyl-D-aspartate glutamate receptor subunit NR1. In the inner plexiform and outer plexiform layers the immunoreactivity of GluR2 and NR1 subunits was significantly increased in subjects with diabetes when compared to the levels found in controls. No significant changes in GluR1 and GluR4 subunit expression were observed.These results suggest that early visual dysfunction in diabetic patients may be due, at least partially, to changes in glutamate receptor subunit expression or distribution. IntroductionDiabetic retinopathy (DR) is a leading cause of blindness in working-age adults in developed countries. The vascular changes that occur in DR are well documented, and include loss of pericytes and endothelial cells, the formation of microaneurysms, basement membrane thickening and blood-retinal barrier breakdown (Cai and Boulton, 2002). In addition to the vascular

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“…The amino acids are involved in several physiological events, including brain development and ageing, in physiological integration among brain structures, and in the processes of learning and memory 12 . Neurotransmitter systems alterations can be implicated in seizures due an increase in their oxidative metabolism or by a decrease in their syntheses and/or release 7,9 .…”

mentioning

confidence: 99%

Lipoic acid effects on glutamate and taurine concentrations in rat hippocampus after pilocarpine-induced seizures

Santos

Campêlo

Freitas³

et al. 2011

Arq. Neuro-Psiquiatr.

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Pilocarpine-induced seizures can be mediated by increases in oxidative stress and by cerebral amino acid changes. The present research suggests that antioxidant compounds may afford some level of neuroprotection against the neurotoxicity of seizures in cellular level. The objective of the present study was to evaluate the lipoic acid (LA) effects in glutamate and taurine contents in rat hippocampus after pilocarpine-induced seizures. Wistar rats were treated intraperitoneally (i.p.) with 0.9% saline (Control), pilocarpine (400 mg/kg, Pilocarpine), LA (10 mg/kg, LA), and the association of LA (10 mg/kg) plus pilocarpine (400 mg/kg), that was injected 30 min before of administration of LA (LA plus pilocarpine). Animals were observed during 24 h. The amino acid concentrations were measured using high-performance liquid chromatograph (HPLC). In pilocarpine group, it was observed a significant increase in glutamate content (37%) and a decrease in taurine level (18%) in rat hippocampus, when compared to control group. Antioxidant pretreatment significantly reduced the glutamate level (28%) and augmented taurine content (32%) in rat hippocampus, when compared to pilocarpine group. Our findings strongly support amino acid changes in hippocampus during seizures induced by pilocarpine, and suggest that glutamate-induced brain damage plays a crucial role in pathogenic consequences of seizures, and imply that strong protective effect could be achieved using lipoic acid through the release or decrease in metabolization rate of taurine amino acid during seizures. Key words: seizures, pilocarpine, amino acids, hippocampus, glutamate, taurine.Efeitos do ácido lipóico nas concentrações de glutamato e taurina no hipocampo de ratos após convulsões induzidas por pilocarpina RESUMO As convulsões induzidas pela pilocarpina podem ser mediadas através do aumento do estresse oxidativo cerebral e das alterações na concentração dos aminoácidos. O presente estudo sugere que compostos antioxidantes podem produzir neuroproteção contra a neurotoxicidade em nível celular causada pelas convulsões. O objetivo deste estudo foi avaliar os efeitos do ácido lipóico (AL) no conteúdo de glutamato e taurina no hipocampo de ratos durante convulsões induzidas por pilocarpina. Ratos Wistar foram tratados por via intraperitoneal com solução salina 0,9% (controle), pilocarpina (400 mg/kg, pilocarpina), AL (10 mg/kg) e com a associação de AL (10 mg/kg); 30 min após com pilocarpina (400 mg/kg), que foi injetada 30 min após a administração de AL (AL + pilocarpina). Os animais foram observados durante 24 horas. As concentrações de aminoácidos foram

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Glutamate receptors in the mammalian central nervous system

Cited by 972 publications

References 388 publications

A Review of Glutamate Receptors I: Current Understanding of Their Biology

A Review of Glutamate Receptors I: Current Understanding of Their Biology

Diabetes changes ionotropic glutamate receptor subunit expression level in the human retina

Lipoic acid effects on glutamate and taurine concentrations in rat hippocampus after pilocarpine-induced seizures

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