Dedeurwaerdere Stefanie, Boets Stephanie, Janssens Pieter, Lavreysen Hilde, Steckler Thomas
Experimental Laboratory of Translational Neuroscience and Otolaryngology, Department of Translational Neurosciences, University of Antwerp, Wilrijk, Belgium,
Acta Neurol Belg. 2015 Sep;115(3):221-32. doi: 10.1007/s13760-014-0407-7. Epub 2014 Dec 25.
Glutamate is the major excitatory neurotransmitter in the brain. The glutamate system plays an important role in the formation of synapses during brain development and synaptic plasticity. Dysfunctions in glutamate regulation may lead to hyperexcitatory neuronal networks and neurotoxicity. Glutamate excess is possibly of great importance in the pathophysiology of several neurological and psychiatric disorders such as epilepsy and schizophrenia. Interestingly, cross talk between these disorders has been well documented: psychiatric comorbidities are frequent in epilepsy and temporal lobe epilepsy is one of the highest risk factors for developing psychosis. Therefore, dysfunctions in glutamatergic neurotransmission might constitute a common pathological mechanism. A major negative feedback system is regulated by the presynaptic group II metabotropic glutamate (mGlu) receptors including mGlu2/3 receptors. These receptors are predominantly localised extrasynaptically in basal ganglia and limbic structures. Hence, mGlu2/3 receptors are an interesting target for the treatment of disorders like epilepsy and schizophrenia. A dysfunction in the glutamate system may be associated with alterations in mGlu2/3 receptor expression. In this review, we describe the localization of mGlu2/3 receptors in the healthy brain of mice, rats and humans. Secondly, changes in mGlu2/3 receptor density of the brain regions affected in epilepsy and schizophrenia are summarised. Increased mGlu2/3 receptor density might represent a compensatory mechanism of the brain to regulate elevated glutamate levels, while reduced mGlu2/3 receptor density in some brain regions may further contribute to the aberrant hyperexcitability. Further research considering the mGlu2/3 receptor can contribute significantly to the understanding of the etiological and therapeutic role of group II mGlu receptor in epilepsy, epilepsy with psychosis and schizophrenia.
谷氨酸是大脑中主要的兴奋性神经递质。谷氨酸系统在大脑发育过程中突触的形成以及突触可塑性方面发挥着重要作用。谷氨酸调节功能障碍可能导致神经元网络过度兴奋和神经毒性。谷氨酸过量在癫痫和精神分裂症等多种神经和精神疾病的病理生理学中可能具有重要意义。有趣的是，这些疾病之间的相互影响已有充分记录：癫痫患者中精神疾病共病很常见，而颞叶癫痫是患精神病的最高风险因素之一。因此，谷氨酸能神经传递功能障碍可能构成一种共同的病理机制。一个主要的负反馈系统由突触前II组代谢型谷氨酸（mGlu）受体调节，包括mGlu2/3受体。这些受体主要位于基底神经节和边缘结构的突触外。因此，mGlu2/3受体是治疗癫痫和精神分裂症等疾病的一个有吸引力的靶点。谷氨酸系统功能障碍可能与mGlu2/3受体表达的改变有关。在这篇综述中，我们描述了mGlu2/3受体在小鼠、大鼠和人类健康大脑中的定位。其次，总结了癫痫和精神分裂症所影响的脑区中mGlu2/3受体密度的变化。mGlu2/3受体密度增加可能代表大脑调节升高的谷氨酸水平的一种代偿机制，而某些脑区中mGlu2/3受体密度降低可能进一步导致异常的过度兴奋。考虑mGlu2/3受体的进一步研究可显著有助于理解II组mGlu受体在癫痫、伴有精神病的癫痫和精神分裂症中的病因学和治疗作用。
