Naskar Saptarnab, Datta Siddhartha, Chattarji Sumantra
National Centre for Biological Sciences, Bangalore, 560065, India.
Department of Psychiatry and Behavioral Sciences, Northwestern University, Feinberg School of Medicine, 303 E Chicago Ave, Chicago, IL, 60610, USA.
Neurobiol Stress. 2022 Mar 18;18:100442. doi: 10.1016/j.ynstr.2022.100442. eCollection 2022 May.
Stress elicits divergent patterns of structural plasticity in the amygdala and hippocampus. Despite these contrasting effects, at least one of the immediate consequences of stress - elevated levels of extracellular glutamate - is similar in both brain areas. This raises the possibility that the contrasting effects of stress on neuronal plasticity is shaped by differences in astrocytic glutamate clearance in these two brain areas. Although astrocytes play a key role in glutamate reuptake, past analyses of, and interventions against, stress-induced plasticity have focused largely on neurons. Hence, we tested the impact of riluzole, which potentiates glutamate clearance by astrocytic glutamate transporters, on principal neurons and astrocytes in the basal amygdala (BA) and hippocampal area CA1. Chronic immobilization stress reduced spine-density on CA1 pyramidal neurons of male rats. Riluzole, administered in the drinking water during chronic stress, prevented this decrease; but, the drug by itself had no effect. In contrast, the same chronic stress enhanced spine-density on BA principal neurons, and this effect, unlike area CA1, was not reversed by riluzole. Strikingly, riluzole treatment alone also caused spinogenesis in the BA. Thus, the same riluzole treatment that prevented the effect of stress on spines in the hippocampus, mimicked its effect in the amygdala. Further, chronic stress and riluzole alone decreased the neuropil volume occupied by astrocytes in both the BA and CA1 area. Riluzole treatment in stressed animals, however, did not reverse or further add to this reduction in either region. Thus, while the effects on astrocytes were similar, neuronal changes were distinct between the two areas following stress, riluzole and the two together. Therefore, similar to the impact of repeated stress, pharmacological potentiation of glutamate clearance, with or without stress, also leads to differential effects on dendritic spines in principal neurons of the amygdala and hippocampus. This highlights differences in the astrocytic glutamate reuptake machinery that are likely to have important functional consequences for stress-induced dysfunction, and its reversal, in two brain areas implicated in stress-related psychiatric disorders.
应激在杏仁核和海马体中引发不同模式的结构可塑性。尽管有这些相反的影响，但应激的至少一个直接后果——细胞外谷氨酸水平升高——在这两个脑区是相似的。这就提出了一种可能性，即应激对神经元可塑性的相反影响是由这两个脑区星形胶质细胞清除谷氨酸的差异所塑造的。虽然星形胶质细胞在谷氨酸再摄取中起关键作用，但过去对应激诱导可塑性的分析和干预主要集中在神经元上。因此，我们测试了利鲁唑（riluzole）对基底杏仁核（BA）和海马体CA1区的主要神经元和星形胶质细胞的影响，利鲁唑可通过星形胶质细胞谷氨酸转运体增强谷氨酸清除。慢性束缚应激降低了雄性大鼠CA1锥体神经元的棘密度。在慢性应激期间通过饮水给予利鲁唑可防止这种降低；但是，该药物本身没有效果。相反，相同的慢性应激增加了BA主要神经元的棘密度，并且与CA1区不同，这种作用并未被利鲁唑逆转。令人惊讶的是，单独使用利鲁唑治疗也会在BA中引起棘生成。因此，相同的利鲁唑治疗在防止应激对海马体棘的影响的同时，在杏仁核中模拟了其作用。此外，慢性应激和单独使用利鲁唑都会减少BA和CA1区中星形胶质细胞占据的神经毡体积。然而，在应激动物中进行利鲁唑治疗并没有逆转或进一步加剧这两个区域的这种减少。因此，虽然对应激对星形胶质细胞的影响是相似的，但在应激、利鲁唑以及两者共同作用后，两个脑区的神经元变化是不同的。因此，与重复应激的影响类似，无论有无应激，谷氨酸清除的药理学增强也会对杏仁核和海马体主要神经元的树突棘产生不同的影响。这突出了星形胶质细胞谷氨酸再摄取机制的差异，这可能对应激相关精神障碍所涉及的两个脑区中应激诱导的功能障碍及其逆转具有重要的功能后果。
