Pidoplichko Volodymyr I, Figueiredo Taiza H, Braga Maria F M, Marini Ann M
Department of Anatomy, Physiology and Genetics, Uniformed Services University of the Health Sciences, Bethesda, MD, United States.
Department of Neurology, Neuroscience, Molecular and Cellular Biology, Graduate School of Nursing, Uniformed Services University of the Health Sciences, Bethesda, MD, United States.
Exp Biol Med (Maywood). 2025 May 15;250:10545. doi: 10.3389/ebm.2025.10545. eCollection 2025.
Epilepsy affects more than 70 million people worldwide. A seizure focus that develops in different cortical brain regions can present as either focal or generalized seizures. Temporal lobe epilepsy is a highly pharmacoresistant form of epilepsy that involves the amygdala, hippocampus with or without hippocampal sclerosis as well as other limbic structures. Loss and/or dysfunction of GABAergic inhibitory neurons play a critical role in tipping the balance toward excitation. Synchronous burst firing is a feature of inhibitory neurons that is thought to regulate and rectify large excitatory neuronal networks in the BLA and is thought to underlie higher cognitive function. Acid sensing ion channels (ASIC) activated by decreases in pH, the presence of ammonium ion or a slight lowering of temperature are present on excitatory and inhibitory neurons and can alter excitability. The net effect of the activation of ASIC1a channels in the BLA is inhibition. ASIC1a channels are active in the basal state, enhancing primarily GABAergic inhibition by direct depolarization of interneurons but also by indirect excitation of interneurons via ASIC1a-mediated depolarization of pyramidal neurons. In this study, we examine the contribution of ASIC1a channel activation on alpha-linolenic acid (ALA)-induced GABAergic inhibitory synchronous burst firing in the BLA. Our results show that ALA initiates inhibitory bursts that are dependent, in part, on the activation of ASIC1a channels that may in turn be mediated by mature brain-derived neurotrophic factor.
癫痫在全球影响着超过7000万人。在不同大脑皮质区域形成的癫痫病灶可表现为局灶性或全身性癫痫发作。颞叶癫痫是一种药物抵抗性很强的癫痫形式，涉及杏仁核、伴有或不伴有海马硬化的海马体以及其他边缘结构。γ-氨基丁酸（GABA）能抑制性神经元的丧失和/或功能障碍在使平衡向兴奋倾斜方面起着关键作用。同步爆发式放电是抑制性神经元的一个特征，被认为可调节和纠正杏仁核基底外侧核（BLA）中的大型兴奋性神经元网络，并被认为是更高认知功能的基础。由pH值降低、铵离子存在或温度略有降低激活的酸敏感离子通道（ASIC）存在于兴奋性和抑制性神经元上，并可改变兴奋性。BLA中ASIC1a通道激活的净效应是抑制。ASIC1a通道在基础状态下活跃，主要通过中间神经元的直接去极化增强GABA能抑制，也通过ASIC1a介导的锥体神经元去极化间接兴奋中间神经元。在本研究中，我们研究了ASIC1a通道激活对BLA中α-亚麻酸（ALA）诱导的GABA能抑制性同步爆发式放电的作用。我们的结果表明，ALA引发抑制性爆发，这部分依赖于ASIC1a通道的激活，而ASIC1a通道的激活可能反过来由成熟的脑源性神经营养因子介导。
