Quinolinic acid effects on amino acid release from the rat cerebral cortex <i>in vitro</i> and <i>in vivo</i>

Connick, J.H.; Stone, T.W.

doi:10.1111/j.1476-5381.1988.tb11474.x

Cited by 65 publications

(35 citation statements)

References 23 publications

(23 reference statements)

Supporting

Mentioning

Contrasting

Order By: Relevance

“…It is possible therefore that the greater sensitivity of CA3 neurones to kainate is partly the result of its acting presynaptically to promote the release of endogenous compounds, which contribute to the excitatory response. Consistent with this idea is the demonstration that kainic acid can promote the release of both glutamate and aspartate from nerve terminals (Collins et al, 1983;Ferkany & Coyle, 1983;Potashner & Gerard, 1983;Connick & Stone, 1988). In the present study we have therefore compared the potency of kainic acid on CA3 pyramidal cells in the normal hippocampal slice and slices prepared from animals pretreated with colchicine to remove the mossy fibre projection.…”

Section: Introductionsupporting

confidence: 65%

Sensitivity of hippocampal neurones to kainic acid, and antagonism by kynurenate

Stone

1990

British J Pharmacology

Self Cite

View full text Add to dashboard Cite

show abstract

Section: Introductionsupporting

confidence: 65%

Sensitivity of hippocampal neurones to kainic acid, and antagonism by kynurenate

Stone

1990

British J Pharmacology

Self Cite

View full text Add to dashboard Cite

show abstract

“…QUIN has been demonstrated to be a neurotoxic compound in several paradigms [5,210]. On the one hand, it can cause glutamate excitotoxicity via the following mechanisms: it can directly activate NMDARs and, in addition to its receptorial effect, it is capable of modulating glutamate release and inhibiting the uptake of glutamate by astrocytes [239][240][241]. Accordingly, the hyperphosphorylation of tau proteins via the overactivation of NMDAR is augmented by QUIN, further contributing to glutamate excitotoxicity in AD [242].…”

Section: Quinolinic Acidmentioning

confidence: 99%

Alzheimer’s Disease: Recent Concepts on the Relation of Mitochondrial Disturbances, Excitotoxicity, Neuroinflammation, and Kynurenines

Zádori

Veres

Szalárdy

et al. 2018

JAD

View full text Add to dashboard Cite

The pathomechanism of Alzheimer's disease (AD) certainly involves mitochondrial disturbances, glutamate excitotoxicity, and neuroinflammation. The three main aspects of mitochondrial dysfunction in AD, i.e., the defects in dynamics, altered bioenergetics, and the deficient transport act synergistically. In addition, glutamatergic neurotransmission is affected in several ways. The balance between synaptic and extrasynaptic glutamatergic transmission is shifted toward the extrasynaptic site contributing to glutamate excitotoxicity, a phenomenon augmented by increased glutamate release and decreased glutamate uptake. quinolinic acid, has been demonstrated to be neurotoxic, promoting glutamate excitotoxicity, reactive oxygen species production, lipid peroxidation, and microglial neuroinflammation, and its abundant presence in AD pathologies has been demonstrated. Finally, the neuroprotective metabolite, kynurenic acid, has been associated with antagonistic effects at glutamate receptors, free radical scavenging, and immunomodulation, giving rise to potential therapeutic implications. This review presents the multiple connections of KYN pathwayrelated alterations to three main domains of AD pathomechanism, such as mitochondrial dysfunction, excitotoxicity, and neuroinflammation, implicating possible therapeutic options.3

show abstract

“…First, the expression of several neuronal proteins involved in the glutamatergic neurotransmission was not changed by CNTF. Second, the increase in the extracellular concentration of other amino acids during QA perfusion (Connick and Stone, 1988) was not significantly different between lenti-CNTF and lenti-LacZ groups. Combined with the third observation that QA induced a significant increase in FDG uptake in all groups, these results demonstrate that the early stimulatory effects of QA on neuronal activity and glutamate release have indeed occurred.…”

Section: Cntf Improves Glutamate Handling and Energy Supplymentioning

confidence: 99%

Ciliary Neurotrophic Factor Activates Astrocytes, Redistributes Their Glutamate Transporters GLAST and GLT-1 to Raft Microdomains, and Improves Glutamate HandlingIn Vivo

Escartin¹,

Brouillet²,

Gubellini³

et al. 2006

J. Neurosci.

111

View full text Add to dashboard Cite

To study the functional role of activated astrocytes in glutamate homeostasis in vivo, we used a model of sustained astrocytic activation in the rat striatum through lentiviral-mediated gene delivery of ciliary neurotrophic factor (CNTF). CNTF-activated astrocytes were hypertrophic, expressed immature intermediate filament proteins and highly glycosylated forms of their glutamate transporters GLAST and GLT-1. CNTF overexpression produced a redistribution of GLAST and GLT-1 into raft functional membrane microdomains, which are important for glutamate uptake. In contrast, CNTF had no detectable effect on the expression of a number of neuronal proteins and on the spontaneous glutamatergic transmission recorded from striatal medium spiny neurons. These results were replicated in vitro by application of recombinant CNTF on a mixed neuron/astrocyte striatal culture. Using microdialysis in the rat striatum, we found that the accumulation of extracellular glutamate induced by quinolinate (QA) was reduced threefold with CNTF. In line with this result, CNTF significantly increased QA-induced [ 18 F]-fluoro-2-deoxyglucose uptake, an indirect index of glutamate uptake by astrocytes. Together, these data demonstrate that CNTF activation of astrocytes in vivo is associated with marked phenotypic and molecular changes leading to a better handling of increased levels of extracellular glutamate. Activated astrocytes may therefore be important prosurvival agents in pathological conditions involving defects in glutamate homeostasis.

show abstract

Quinolinic acid effects on amino acid release from the rat cerebral cortex in vitro and in vivo

Cited by 65 publications

References 23 publications

Sensitivity of hippocampal neurones to kainic acid, and antagonism by kynurenate

Sensitivity of hippocampal neurones to kainic acid, and antagonism by kynurenate

Alzheimer’s Disease: Recent Concepts on the Relation of Mitochondrial Disturbances, Excitotoxicity, Neuroinflammation, and Kynurenines

Ciliary Neurotrophic Factor Activates Astrocytes, Redistributes Their Glutamate Transporters GLAST and GLT-1 to Raft Microdomains, and Improves Glutamate HandlingIn Vivo

Contact Info

Product

Resources

About