Regulation of GABAergic neurotransmission by purinergic receptors in brain physiology and disease.

IF 3 4区 医学 Q2 NEUROSCIENCES Purinergic Signalling Pub Date : 2024-07-24 DOI:10.1007/s11302-024-10034-x
Guilherme Juvenal, Guilherme Shigueto Vilar Higa, Lucas Bonfim Marques, Thais Tessari Zampieri, Felipe José Costa Viana, Luiz R Britto, Yong Tang, Peter Illes, Francesco di Virgilio, Henning Ulrich, Roberto de Pasquale
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Abstract

Purinergic receptors regulate the processing of neural information in the hippocampus and cerebral cortex, structures related to cognitive functions. These receptors are activated when astrocytic and neuronal populations release adenosine triphosphate (ATP) in an autocrine and paracrine manner, following sustained patterns of neuronal activity. The modulation by these receptors of GABAergic transmission has only recently been studied. Through their ramifications, astrocytes and GABAergic interneurons reach large groups of excitatory pyramidal neurons. Their inhibitory effect establishes different synchronization patterns that determine gamma frequency rhythms, which characterize neural activities related to cognitive processes. During early life, GABAergic-mediated synchronization of excitatory signals directs the experience-driven maturation of cognitive development, and dysfunctions concerning this process have been associated with neurological and neuropsychiatric diseases. Purinergic receptors timely modulate GABAergic control over ongoing neural activity and deeply affect neural processing in the hippocampal and neocortical circuitry. Stimulation of A2 receptors increases GABA release from presynaptic terminals, leading to a considerable reduction in neuronal firing of pyramidal neurons. A1 receptors inhibit GABAergic activity but only act in the early postnatal period when GABA produces excitatory signals. P2X and P2Y receptors expressed in pyramidal neurons reduce the inhibitory tone by blocking GABAA receptors. Finally, P2Y receptor activation elicits depolarization of GABAergic neurons and increases GABA release, thus favoring the emergence of gamma oscillations. The present review provides an overall picture of purinergic influence on GABAergic transmission and its consequences on neural processing, extending the discussion to receptor subtypes and their involvement in the onset of brain disorders, including epilepsy and Alzheimer's disease.

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嘌呤能受体在大脑生理和疾病中对 GABA 能神经传递的调控。
嘌呤能受体调节海马和大脑皮层这些与认知功能有关的结构中神经信息的处理。当神经元持续活动时,星形胶质细胞和神经元群以自分泌和旁分泌的方式释放三磷酸腺苷(ATP)时,这些受体就会被激活。人们最近才开始研究这些受体对 GABA 能传导的调节作用。星形胶质细胞和 GABA 能中间神经元通过它们的分支到达大群兴奋性锥体神经元。它们的抑制作用建立了不同的同步模式,决定了伽马频率节律,而伽马频率节律是与认知过程有关的神经活动的特征。在生命早期,GABA 能介导的兴奋信号同步引导着经验驱动的认知发展成熟,而这一过程的功能障碍与神经和神经精神疾病有关。嘌呤能受体能及时调节 GABA 能对持续神经活动的控制,并深刻影响海马和新皮层回路的神经处理过程。刺激 A2 受体会增加突触前终端的 GABA 释放,从而显著降低锥体神经元的神经元发射。A1 受体抑制 GABA 能活动,但只在 GABA 产生兴奋信号的出生后早期发挥作用。在锥体神经元中表达的 P2X 和 P2Y 受体通过阻断 GABAA 受体来降低抑制音调。最后,P2Y 受体激活会引起 GABA 能神经元去极化,增加 GABA 的释放,从而有利于伽马振荡的出现。本综述全面介绍了嘌呤能对 GABA 能传导的影响及其对神经处理的后果,并将讨论扩展到受体亚型及其与癫痫和阿尔茨海默病等脑部疾病的发病关系。
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来源期刊
Purinergic Signalling
Purinergic Signalling 医学-神经科学
CiteScore
6.60
自引率
17.10%
发文量
75
审稿时长
6-12 weeks
期刊介绍: Nucleotides and nucleosides are primitive biological molecules that were utilized early in evolution both as intracellular energy sources and as extracellular signalling molecules. ATP was first identified as a neurotransmitter and later as a co-transmitter with all the established neurotransmitters in both peripheral and central nervous systems. Four subtypes of P1 (adenosine) receptors, 7 subtypes of P2X ion channel receptors and 8 subtypes of P2Y G protein-coupled receptors have currently been identified. Since P2 receptors were first cloned in the early 1990’s, there is clear evidence for the widespread distribution of both P1 and P2 receptor subtypes in neuronal and non-neuronal cells, including glial, immune, bone, muscle, endothelial, epithelial and endocrine cells.
期刊最新文献
Correction to: Preparation and preliminary evaluation of a tritium-labeled allosteric P2X4 receptor antagonist. Machine learning-aided search for ligands of P2Y6 and other P2Y receptors. Purinergic regulation of pulmonary vascular tone. Role of ecto-5'-nucleotidase in bladder function activity and smooth muscle contractility. Unexpected role of microglia and P2Y12 in the induction of and emergence from anesthesia.
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