成瘾过程中海马神经元星形胶质细胞相互作用的数学模型

M. Borjkhani, A. Mahdavi, F. Bahrami
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引用次数: 3

摘要

成瘾是一种慢性疾病,成瘾者不顾其负面后果而强迫性地寻求药物。由于海马在学习和记忆中的重要性,它在成瘾中具有不可避免的作用。海马细胞的任何修饰都会改变NAc中的多巴胺水平和VTA多巴胺能细胞的放电率。为了更好地理解细胞水平上的成瘾,我们提出了海马三方突触的数学模型。该模型可以显示成瘾下突触的一些功能,这些功能可能有助于药物寻求和复发行为。该模型基于药物滥用期间突触间隙中谷氨酸的改变。实验研究表明,在药物滥用期间,NMD依赖性AR突触传递增加。根据我们的模拟结果,星形胶质细胞的功能障碍在成瘾的启动中起着重要作用。由于健康的星形胶质细胞具有对突触相互作用的全面控制,它可能用于治疗成瘾相关行为。此外,我们可以得出结论,成瘾导致突触后信号异常,如NMDA电流。此外,我们可能认为药物诱导d -丝氨酸增强突触裂电位、突触后钙内流和LTP。
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A mathematical model for neuron astrocytes interactions in hippocampus during addiction
Addiction is a chronic disorder whereby addicted individuals compulsively engage in drug seeking despite its negative consequences. Hippocampus has unavoidable role in addiction because of its importance in learning and memory. Any modification of hippocampal cells alters dopamine levels in NAc and firing rates of VTA dopaminergic cells. In order to have a better understanding of the addiction in cellular level, we present a mathematical model of a tripartite synapse in hippocampus. The proposed model can show some functions of synapses under addiction that may contribute to drug seeking and relapse behaviors. The model is based on glutamate alterations in synaptic cleft during drug abuse. Experimental studies suggest that during drug abuse, NMD AR dependent synaptic transmission is increased. According to our simulation results, dysfunction of astrocyte has a significant role in initiating addiction. Since healthy astrocytes has a comprehensive control over synaptic interactions it may use to treat addicted related behaviors. Also, we may conclude that addiction causes abnormalities on postsynaptic signaling such as NMDA currents. Furthermore, we may suggest that drug induced D-serine enhancement in synaptic cleft potentiate post synaptic calcium influx and LTP.
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