Abstract：
The endocannabinoid system (ECS) regulates neurotransmission linked to synaptic plasticity, cognition, and emotion. While it has been demonstrated that dysregulation of the ECS in adulthood is relevant not only to central nervous system (CNS) disorders such as autism spectrum disorder, cognitive dysfunction, and depression but also to brain function, there are few studies on how dysregulation of the ECS in the neonatal period affects the manifestation and pathophysiology of CNS disorders later in life. In this study, DO34, a diacylglycerol lipase alpha (DAGLα) inhibitor affecting endocannabinoid 2-AG production, was injected into C57BL/6N male mice from postnatal day (PND) 7 to PND 10, inducing dysregulation of the ECS in the neonatal period. Subsequently, we examined whether it affects neuronal function in adulthood through electrophysiological and behavioral evaluation. DO34-injected mice showed significantly decreased cognitive functions, attributed to impairment of hippocampal synaptic plasticity. The findings suggest that regulation of ECS activity in the neonatal period may induce enduring effects on adult brain function.
摘要：
内源性大麻素系统（ECS）调节与突触可塑性相关的神经传递，认知，和情感。虽然已经证明，在成年期ECS的失调不仅与中枢神经系统（CNS）疾病有关，如自闭症谱系障碍，认知功能障碍，和抑郁症，还有大脑功能，关于新生儿期ECS失调如何影响后期中枢神经系统疾病的表现和病理生理学的研究很少。在这项研究中,DO34，一种影响内源性大麻素2-AG生产的二酰甘油脂肪酶α（DAGLα）抑制剂，从出生后（PND）7天到PND10天将其注射到C57BL/6N雄性小鼠中，从而在新生儿期诱导ECS的失调。随后，我们通过电生理和行为评估来研究它是否会影响成年期的神经元功能。注射DO34的小鼠表现出明显的认知功能下降，归因于海马突触可塑性受损。研究结果表明，新生儿期ECS活性的调节可能会对成人的大脑功能产生持久的影响。
