Higher susceptibility of taurine-deficient rats to seizures induced by 4-aminopyridine

Pasantes‐Morales, Herminia; Arzate, M.E.; Quesada, O.; Huxtable, Ryan J.

doi:10.1016/0028-3908(87)90123-7

Cited by 22 publications

(12 citation statements)

References 16 publications

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“…Our main observations suggest that taurine at more moderate doses can potentiate the anticonvulsive actions of drugs acting on GABA A receptors, in line with previous observations that describe modulating taurine effects on ectopically expressed GABA A receptors. However, animal experiments revealed that inhibition of taurine transport decreased the seizure threshold 45 and reduced the sensitivity to anticonvulsant drugs, 26 but both studies investigated the effect of chronic taurine transport inhibition, which diminished taurine uptake over the blood-brain barrier and thus reduced the overall taurine content in the brain. However, we are aware that our experiments provide rather indirect evidence for a modulatory taurine binding-site and that further experiments are required to establish mechanisms and molecular details of this proposed allosteric interaction.…”

Section: Discussionmentioning

confidence: 99%

Taurine potentiates the anticonvulsive effect of theGABA_Aagonist muscimol and pentobarbital in the immature mouse hippocampus

2019

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Summary Objective The high incidence of epileptic seizures in neonates and their frequent refractoriness to pharmacologic therapies require identification of new therapeutical options. Therefore, we investigated whether the modulatory effect of taurine on γ‐aminobutyric acid (GABA)A receptors can enhance the anticonvulsive potential of the GABAA receptor agonist muscimol and of the barbiturate pentobarbital. Methods We performed field potential recordings in in toto hippocampus preparations of immature (postnatal days 4‐7) C57Bl/6 mouse pups. Spontaneous epileptiform activity was induced by the continuous presence of the potassium channel blocker 4‐aminopyridine and the glycinergic antagonist strychnine in Mg2+‐free solutions. Results Bath application of 0.1 μmol/L muscimol increases the occurrence of recurrent epileptiform discharges, whereas they are significantly attenuated in a dose‐dependent manner by muscimol in concentrations between 0.5 and 5 μmol/L. Taurine at concentrations between 0.1 and 0.5 mmol/L induces a proconvulsive effect, but upon coapplication, it significantly augments the anticonvulsive effect of moderate muscimol doses (0.5‐1 μmol/L). In addition, the anticonvulsive effect of 100 and 200 μmol/L pentobarbital is increased significantly in the presence of 0.5 μmol/L taurine. Significance These observations demonstrate that taurine can indeed enhance the anticonvulsive effects of muscimol and pentobarbital, suggesting that taurine may act as a positive modulator on GABAA receptors. Thus, interfering with the modulatory taurine binding site of GABAA receptors or the interstitial taurine concentration may provide new therapeutical options for anticonvulsive therapies in neonates.

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Section: Discussionmentioning

confidence: 99%

Taurine potentiates the anticonvulsive effect of theGABA_Aagonist muscimol and pentobarbital in the immature mouse hippocampus

2019

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“…Interestingly, impairments in taurinergic tonus have been implicated in several pathological conditions, including loss of taurine from epileptic foci in humans (Perry and Hansen ) and a higher susceptibility of taurine‐deficient rats to seizures (Pasantes‐Morales et al . ). Low levels of taurine have been reported in the brains of AD patients (e.g., Csernansky et al .…”

Section: Neuronal Hyperpolarization As a Therapeutic Approachmentioning

confidence: 97%

Deregulation of excitatory neurotransmission underlying synapse failure in Alzheimer's disease

Paula-Lima

Brito-Moreira

Ferreira

2013

Journal of Neurochemistry

155

119

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Alzheimer′s disease (AD) is the most common form of dementia in the elderly. Memory loss in AD is increasingly attributed to soluble oligomers of the amyloid-b peptide (AbOs), toxins that accumulate in AD brains and target particular synapses. Glutamate receptors appear to be centrally involved in synaptic targeting by AbOs. Once bound to neurons, AbOs dysregulate the activity and reduce the surface expression of both N-methyl-D-aspartate (NMDA) and 2-amino-3-(3-hydroxy-5-methyl-isoxazol-4-yl)propanoic acid (AMPA) types of glutamate receptors, impairing signaling pathways involved in synaptic plasticity. In the extracellular milieu, AbOs promote accumulation of the excitatory amino acids, glutamate and D-serine. This leads to overactivation of glutamate receptors, triggering abnormal calcium signals with noxious impacts on neurons. Here, we review key findings linking AbOs to deregulated glutamate neurotransmission and implicating this as a primary mechanism of synapse failure in AD. We also discuss strategies to counteract the impact of AbOs on excitatory neurotransmission. In particular, we review evidence showing that inducing neuronal hyperpolarization via activation of inhibitory GABA A receptors prevents AbOinduced excitotoxicity, suggesting that this could comprise a possible therapeutic approach in AD.

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“…Evidence for an increase in glutamate level during seizures has been demonstrated by microdialysis studies in several different models of experimental epilepsy (Kam et al, 1999;Kaura et al, 1995;Ueda and Tsuru, 1994) as well as in humans (During and Spencer, 1993). 4-Aminopyridine (4-AP) is a potent convulsive drug that blocks voltage-activated K + channels and its systemic or intracerebral administration induces generalized tonic convulsions in humans and other species (Glover, 1982;Milhaly et al, 1990;Pasantes-Morales and Arzate, 1981;Pasantes-Morales et al, 1987;Spyker et al, 1980;Tapia and Sitges, 1982).…”

Section: Introductionmentioning

confidence: 97%

Simultaneous glutamate and EEG activity measurements during seizures in rat hippocampal region with the use of an electrochemical biosensor

Morales‐Villagrán

Medina‐Ceja

López-Pérez

2008

Journal of Neuroscience Methods

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Higher susceptibility of taurine-deficient rats to seizures induced by 4-aminopyridine

Cited by 22 publications

References 16 publications

Taurine potentiates the anticonvulsive effect of theGABA_Aagonist muscimol and pentobarbital in the immature mouse hippocampus

Taurine potentiates the anticonvulsive effect of theGABA_Aagonist muscimol and pentobarbital in the immature mouse hippocampus

Deregulation of excitatory neurotransmission underlying synapse failure in Alzheimer's disease

Simultaneous glutamate and EEG activity measurements during seizures in rat hippocampal region with the use of an electrochemical biosensor

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Higher susceptibility of taurine-deficient rats to seizures induced by 4-aminopyridine

Cited by 22 publications

References 16 publications

Taurine potentiates the anticonvulsive effect of theGABAAagonist muscimol and pentobarbital in the immature mouse hippocampus

Taurine potentiates the anticonvulsive effect of theGABAAagonist muscimol and pentobarbital in the immature mouse hippocampus

Deregulation of excitatory neurotransmission underlying synapse failure in Alzheimer's disease

Simultaneous glutamate and EEG activity measurements during seizures in rat hippocampal region with the use of an electrochemical biosensor

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Product

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Taurine potentiates the anticonvulsive effect of theGABA_Aagonist muscimol and pentobarbital in the immature mouse hippocampus

Taurine potentiates the anticonvulsive effect of theGABA_Aagonist muscimol and pentobarbital in the immature mouse hippocampus