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Maturation of the Endocannabinoid System in the Medial Prefrontal Cortex and the Effect of Perinatal Cananbinoid Exposure- [electronic resource]

자료유형: 학위논문파일 국외

최종처리일시: 20240214101925

ISBN: 9798380851473

DDC: 616

저자명: Murphy Green, Michelle.

서명/저자: Maturation of the Endocannabinoid System in the Medial Prefrontal Cortex and the Effect of Perinatal Cananbinoid Exposure - [electronic resource]

발행사항: [S.l.]: : Indiana University., 2023

발행사항: Ann Arbor : : ProQuest Dissertations & Theses,, 2023

형태사항: 1 online resource(81 p.)

주기사항: Source: Dissertations Abstracts International, Volume: 85-05, Section: B.

주기사항: Advisor: Mackie, Kenneth.

학위논문주기: Thesis (Ph.D.)--Indiana University, 2023.

사용제한주기: This item must not be sold to any third party vendors.

초록/해제: 요약The endocannabinoid system (ECS) is a widespread neuromodulatory system that is present from early stages of prenatal development and plays a critical role in central nervous system development. Additionally, the ECS also mediates the effects of exogenous cannabinoids, like delta-9-tetrahydrocannabinol (THC), the primary psychoactive/intoxicating component of cannabis. Therefore, early life cannabinoid exposure, through inappropriate activation of the ECS, could have severe effects on the immature brain and the development of neural circuitry. Furthermore, cannabis is the most widely used illicit drug in the United States with usage increasing in correlation with increasing legalization of medical and recreational cannabis use. Therefore, understanding the effects of cannabis use across all age ranges is of increasing relevance and importance. As cannabis use is widely perceived as less harmful in comparison to other drugs of abuse, there is a growing population of women who continue to use cannabis throughout their pregnancies and during lactation. However, the impact of this drug exposure on the offspring's neurodevelopment is still unknown, but adverse effects are strongly suggested due to findings that exogenous cannabinoids, like THC, can cross the placenta and are found in breast milk. Early studies have found an association between cannabis use during pregnancy and increased rates of stillbirth and preterm birth as well as impairments in fetal growth and cognitive function. Furthermore, the perinatal period of development, the time immediately before and after birth, is a critical period of neurological development and is especially vulnerable to adverse effects due to early life cannabis exposure. During this time GABA transitions from its immature excitatory state to its mature inhibitory state due to an increased expression of the KCC2 K+/Cl- co-transporter. Alterations in the timing of the GABA switch could have far-reaching effects on the functioning of the central nervous system and may lead to neurological disorders. The research conducted within this dissertation can be divided into three main projects: 1) the effect of in-utero cannabinoid exposure on cortical function in the mPFC, 2) the effect of perinatal cannabinoid exposure on KCC2 and the GABA switch, and 3) sex-specific developmental changes to the mPFC and key molecules of the endocannabinoid system.