Influence of Chronic Electroconvulsive Seizures on Plasticity-Associated Gene Expression and Perineuronal Nets Within the Hippocampi of Young Adult and Middle-Aged Sprague-Dawley Rats.
Influence of Chronic Electroconvulsive Seizures on Plasticity-Associated Gene Expression and Perineuronal Nets Within the Hippocampi of Young Adult and Middle-Aged Sprague-Dawley Rats.
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DOI：
10.1093/ijnp/pyad008
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发表时间：
2023-04-17
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电惊厥发作疗法常用于治疗难治性和老年抑郁症。然而，确定慢性电惊厥发作（ECS）靶点的临床前研究主要集中在年轻成年的动物模型上。鉴于慢性ECS行为效应中涉及的转录、神经源性和神经可塑性机制本身表现出年龄依赖性调节，慢性ECS的分子和细胞靶点是否随年龄而变化仍不清楚。我们让年轻成年大鼠（2-3个月）和中年雄性大鼠（12-13个月）进行假或慢性ECS，并评估绝望样行为、海马基因表达、海马神经发生以及细胞外基质、鞘膜和神经元周围净数的神经可塑性变化。慢性ECS减少了两个年龄段的绝望样行为，并伴有活动依赖性和营养因子基因表达的重叠和独特变化。尽管慢性ECS对两个年龄的静态神经祖细胞数量有相似的影响，但海马祖细胞增殖的最终增加在青年成年期明显更高。我们注意到，仅在青年成年期慢性ECS后，reelin⁺的细胞数下降。相比之下，慢性ECS后，在海马中观察到包裹parvalbumin +神经元的周围神经元网数的年龄不变、强大的溶解。我们的研究结果表明，年龄是决定慢性ecs诱发的海马分子和细胞变化性质的关键变量。这提出了一种有趣的可能性，即慢性ECS可能需要不同的，以及重叠的机制，以年龄依赖的方式驱动抗抑郁样的行为改变。
Electroconvulsive seizure therapy is often used in both treatment-resistant and geriatric depression. However, preclinical studies identifying targets of chronic electroconvulsive seizure (ECS) are predominantly focused on animal models in young adulthood. Given that putative transcriptional, neurogenic, and neuroplastic mechanisms implicated in the behavioral effects of chronic ECS themselves exhibit age-dependent modulation, it remains unknown whether the molecular and cellular targets of chronic ECS vary with age. We subjected young adult (2–3 months) and middle-aged (12–13 months), male Sprague Dawley rats to sham or chronic ECS and assessed for despair-like behavior, hippocampal gene expression, hippocampal neurogenesis, and neuroplastic changes in the extracellular matrix, reelin, and perineuronal net numbers. Chronic ECS reduced despair-like behavior at both ages, accompanied by overlapping and unique changes in activity-dependent and trophic factor gene expression. Although chronic ECS had a similar impact on quiescent neural progenitor numbers at both ages, the eventual increase in hippocampal progenitor proliferation was substantially higher in young adulthood. We noted a decline in reelin⁺ cell numbers following chronic ECS only in young adulthood. In contrast, an age-invariant, robust dissolution of perineuronal net numbers that encapsulate parvalbumin⁺ neurons in the hippocampus were observed following chronic ECS. Our findings indicate that age is a key variable in determining the nature of chronic ECS-evoked molecular and cellular changes in the hippocampus. This raises the intriguing possibility that chronic ECS may recruit distinct, as well as overlapping, mechanisms to drive antidepressant-like behavioral changes in an age-dependent manner.
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