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去除卵巢激素对胆碱能毒蕈碱受体的影响:检测前脉冲抑制和受体结合

The Impact of Removal of Ovarian Hormones on Cholinergic Muscarinic Receptors: Examining Prepulse Inhibition and Receptor Binding.

作者信息

Ch'ng Sarah S, Walker Adam J, McCarthy Madeleine, Le Thien-Kim, Thomas Natalie, Gibbons Andrew, Udawela Madhara, Kusljic Snezana, Dean Brian, Gogos Andrea

机构信息

Florey Institute of Neuroscience and Mental Health, University of Melbourne, Parkville, VIC 3010, Australia.

IMPACT, The Institute for Mental and Physical Health and Clinical Translation, School of Medicine, Deakin University and Barwon Health, Geelong, VIC 3220, Australia.

出版信息

Brain Sci. 2020 Feb 17;10(2):106. doi: 10.3390/brainsci10020106.

Abstract

Ovarian hormones, such as estrogens and progesterone, are known to exert beneficial effects on cognition and some psychiatric disorders. The basis of these effects is not fully understood, but may involve altered cholinergic neurotransmission. This study aimed to investigate how a lack of ovarian hormones would impact muscarinic receptor-induced deficits in prepulse inhibition (PPI) and muscarinic receptor density in several brain regions. Adult female rats were either ovariectomized, to remove the source of ovarian hormones, or left intact (sham-operated). PPI is a measure of sensorimotor gating that is typically impaired in schizophrenia patients, and similar deficits can be induced in rats by administering scopolamine, a muscarinic receptor antagonist. Our results revealed no significant effects of ovariectomy on PPI after saline or scopolamine treatment. Autoradiography was performed to measure cholinergic muscarinic receptor binding density using [H]-pirenzepine, [H]-AF-DX, and [H]-4-DAMP, to label M, M/M, and M receptors, respectively. We examined the amygdala, caudate putamen, dorsal hippocampus, motor cortex, retrosplenial cortex, and ventromedial hypothalamus. There were no significant group differences in any region for any muscarinic receptor type. These results suggest that removing peripheral ovarian hormones does not influence the cholinergic muscarinic receptor system in the context of PPI or receptor binding density.

摘要

已知雌激素和孕酮等卵巢激素对认知和某些精神疾病具有有益作用。这些作用的基础尚未完全了解,但可能涉及胆碱能神经传递的改变。本研究旨在探讨缺乏卵巢激素如何影响毒蕈碱受体诱导的前脉冲抑制(PPI)缺陷以及几个脑区的毒蕈碱受体密度。成年雌性大鼠要么接受卵巢切除术以去除卵巢激素的来源,要么保持完整(假手术)。PPI是一种感觉运动门控的测量指标,精神分裂症患者通常存在受损情况,通过给予毒蕈碱受体拮抗剂东莨菪碱可在大鼠中诱导出类似的缺陷。我们的结果显示,在给予生理盐水或东莨菪碱治疗后,卵巢切除术对PPI没有显著影响。使用[H]-哌仑西平、[H]-AF-DX和[H]-4-DAMP分别标记M、M/M和M受体,通过放射自显影术测量胆碱能毒蕈碱受体结合密度。我们检查了杏仁核、尾状壳核、背侧海马体、运动皮层、压后皮质和腹内侧下丘脑。对于任何毒蕈碱受体类型而言,各脑区均未观察到显著的组间差异。这些结果表明,在PPI或受体结合密度方面,去除外周卵巢激素不会影响胆碱能毒蕈碱受体系统。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/72be/7071400/0ff29b351693/brainsci-10-00106-g001.jpg

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