Alteration of purinergic P2X4 and P2X7 receptor expression in rats with temporal-lobe epilepsy induced by pilocarpine

Doná, Flávia; Ulrich, Henning; Persike, Daniele Suzete; Conceição, Isaltino Marcelo; Blini, João Paulo; Cavalheiro, Ésper A.; Fernandes, Maria José da Silva

doi:10.1016/j.eplepsyres.2008.10.008

Cited by 74 publications

(82 citation statements)

References 64 publications

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“…As further proof for such mechanism, injection of high doses of ATP into rat cortex promoted an increase in seizure occurrence, which could be antagonized by suramin [94]. Hippocampi from chronic epileptic rats demonstrated elevated P2X7 receptor expression and abnormal responses to ATP, suggesting a possible participation of this system in the pathophysiology of epilepsy [95]. Potent drugs are administrated in high doses in rats and mice to promote sequential seizures and behavioral and electrographic changes [62].…”

Section: Epilepsymentioning

confidence: 94%

“…In a rat epilepsy model, kainate application elevated microglial purinergic receptor expression, mainly P2X7 and P2Y12 receptor subtypes. Both receptors are associated with the active state of microglia, inducing inflammatory responses and microglia migration, respectively [95]. In a temporal lobe epilepsy model induced by pilocarpine injection, P2X4 receptor expression was significantly reduced in pyramidal neurons reflecting a neuronal loss in a chronic status, while elevated P2X7 receptor expression was observed in glial cells suggesting again its participation in the inflammatory response [95].…”

Section: Epilepsymentioning

confidence: 99%

“…Both receptors are associated with the active state of microglia, inducing inflammatory responses and microglia migration, respectively [95]. In a temporal lobe epilepsy model induced by pilocarpine injection, P2X4 receptor expression was significantly reduced in pyramidal neurons reflecting a neuronal loss in a chronic status, while elevated P2X7 receptor expression was observed in glial cells suggesting again its participation in the inflammatory response [95]. Oses [96] observed a decrease in P2X receptor expression in rat hippocampus following convulsive periods which may be associated with progressing neurodegeneration and seizure worsening during epilepsy.…”

Section: Epilepsymentioning

confidence: 99%

“…Oses [96] observed a decrease in P2X receptor expression in rat hippocampus following convulsive periods which may be associated with progressing neurodegeneration and seizure worsening during epilepsy. However, adenosine acting through A1 receptors in an epilepsy model induced by pilocarpine promoted significant protection against seizures [95,97]. As a possible mechanism, adenosine participates in cell proliferation regulation and apoptosis eliminating useless and damaged cells during repair, without the necessity of neurotoxic mediators or immunomodulators.…”

Section: Epilepsymentioning

confidence: 99%

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Perspectives of purinergic signaling in stem cell differentiation and tissue regeneration

Glaser

Cappellari

Pillat

et al. 2011

Purinergic Signalling

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Replacement of lost or dysfunctional tissues by stem cells has recently raised many investigations on therapeutic applications. Purinergic signaling has been shown to regulate proliferation, differentiation, cell death, and successful engraftment of stem cells originated from diverse origins. Adenosine triphosphate release occurs in a controlled way by exocytosis, transporters, and lysosomes or in large amounts from damaged cells, which is then subsequently degraded into adenosine. Paracrine and autocrine mechanisms induced by immune responses present critical factors for the success of stem cell therapy. While P1 receptors generally exert beneficial effects including anti-inflammatory activity, P2 receptor-mediated actions depend on the subtype of stimulated receptors and localization of tissue repair. Pro-inflammatory actions and excitatory tissue damages mainly result from P2X7 receptor activation, while other purinergic receptor subtypes participate in proliferation and differentiation, thereby providing adequate niches for stem cell engraftment and novel mechanisms for cell therapy and endogenous tissue repair. Therapeutic applications based on regulation of purinergic signaling are foreseen for kidney and heart muscle regeneration, Clara-like cell replacement for pulmonary and bronchial epithelial cells as well as for induction of neurogenesis in case of neurodegenerative diseases.

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Section: Epilepsymentioning

confidence: 94%

Section: Epilepsymentioning

confidence: 99%

Section: Epilepsymentioning

confidence: 99%

Section: Epilepsymentioning

confidence: 99%

See 2 more Smart Citations

Perspectives of purinergic signaling in stem cell differentiation and tissue regeneration

Glaser

Cappellari

Pillat

et al. 2011

Purinergic Signalling

Self Cite

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show abstract

“…A previous study by our group suggests the participation of adenosine 5′-triphosphate (ATP) in changes of [Ca 2+ ] i in the hippocampus of epileptic rats, probably by activation of P2X 7 receptors [9]. An increase in P2X 7 receptor expression was observed in the hippocampus of TLE rats, primarily in glial cells and glutamatergic nerve terminals [10], suggesting participation of this receptor in inflammatory response and excitotoxic processes during epileptogenesis.…”

Section: Introductionmentioning

confidence: 90%

Variations of ATP and its metabolites in the hippocampus of rats subjected to pilocarpine-induced temporal lobe epilepsy

Doná

Conceição

Ulrich

et al. 2016

Purinergic Signalling

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Although purinergic receptor activity has lately been associated with epilepsy, little is known about the exact role of purines in epileptogenesis. We have used a rat model of temporal lobe epilepsy induced by pilocarpine to study the dynamics of purine metabolism in the hippocampus during different times of status epilepticus (SE) and the chronic phase. Concentrations of adenosine 5′-triphosphate (ATP), adenosine diphosphate (ADP), adenosine monophosphate (AMP), and adenosine in normal and epileptic rat hippocampus were determined by microdialysis in combination with high-performance liquid chromatography (HPLC). Extracellular ATP concentrations did not vary along 4 h of SE onset. However, AMP concentration was elevated during the second hour, whereas ADP and adenosine concentrations augmented during the third and fourth hour following SE. During chronic phase, extracellular ATP, ADP, AMP, and adenosine concentrations decreased, although these levels again increased significantly during spontaneous seizures. These results suggest that the increased turnover of ATP during the acute period is a compensatory mechanism able to reduce the excitatory role of ATP. Increased adenosine levels following 4 h of SE may contribute to block seizures. On the other hand, the reduction of purine levels in the hippocampus of chronic epileptic rats may result from metabolic changes and be part of the mechanisms involved in the onset of spontaneous seizures. This work provides further insights into purinergic signaling during establishment and chronic phase of epilepsy.

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Purinergic signaling in epilepsy

Rassendren

Audinat

2016

J of Neuroscience Research

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Until recently, analysis of the mechanisms underlying epilepsy was centered on neuron dysfunctions. Accordingly, most of the available pharmacological treatments aim at reducing neuronal excitation or at potentiating neuronal inhibition. These therapeutic options can lead to obvious secondary effects, and, moreover, seizures cannot be controlled by any known medication in one-third of the patients. A purely neurocentric view of brain functions and dysfunctions has been seriously questioned during the past 2 decades because of the accumulation of experimental data showing the functional importance of reciprocal interactions between glial cells and neurons. In the case of epilepsy, our current knowledge of the human disease and analysis of animal models clearly favor the involvement of astrocytes and microglial cells during the progression of the disease, including at very early stages, opening the way to the identification of new therapeutic targets. Purinergic signaling is a fundamental feature of neuron-glia interactions, and increasing evidence indicates that modifications of this pathway contribute to the functional remodeling of the epileptic brain. This Review discusses the recent experimental results indicating the roles of astrocytic and microglial P2X and P2Y receptors in epilepsy. © 2016 Wiley Periodicals, Inc.

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Alteration of purinergic P2X4 and P2X7 receptor expression in rats with temporal-lobe epilepsy induced by pilocarpine

Cited by 74 publications

References 64 publications

Perspectives of purinergic signaling in stem cell differentiation and tissue regeneration

Perspectives of purinergic signaling in stem cell differentiation and tissue regeneration

Variations of ATP and its metabolites in the hippocampus of rats subjected to pilocarpine-induced temporal lobe epilepsy

Purinergic signaling in epilepsy

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