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对梅纳特基底核进行深部脑刺激:刺激模式和持续时间对痴呆大鼠模型学习能力的影响。

Deep brain stimulation of nucleus basalis of meynert: Effect of stimulation mode and duration on learning in rat model of dementia.

作者信息

Kumbhare Deepak, Rajagopal Megan, Toms Jamie, Freelin Anne, Weistroffer George, McComb Nicholas, Karnam Sindhu, Azghadi Adel, Murnane Kevin S, Baron Mark S, Holloway Kathryn L

机构信息

Department of Neurosurgery, Louisiana State University Health Science Center.

Department of Neurosurgery, Virginia Commonwealth University Health System.

出版信息

Behav Neurosci. 2025 Aug-Oct;139(4-5):202-215. doi: 10.1037/bne0000625. Epub 2025 Jun 9.

Abstract

Deep brain stimulation (DBS) of the nucleus basalis of Meynert (NBM) has been preliminarily investigated as a potential treatment for dementia. The degeneration of NBM cholinergic neurons is a pathological feature of many forms of dementia. Although NBM stimulation has been demonstrated to improve learning, the ideal parameters for NBM stimulation have not been elucidated. This study assesses the differential effects of varying stimulation patterns and duration on learning in a dementia rat model with cholinergic deficits. 192-IgG saporin (SAP) or Dulbecco's phosphate buffered saline was injected into the NBM to produce dementia in rats. Next, all rats underwent unilateral implantation of a DBS electrode in the NBM. The experimental groups consisted of (a) normal, (b) untreated SAP-injected rats with cholinergic deficits, and (c) SAP rats receiving NBM DBS. The stimulation paradigms included testing different modes (tonic and burst) and durations (1 hr, 5 hr, and 24 hr/day) over 10 daily sessions. Memory was assessed using two established learning paradigms: novel object recognition and auditory operant chamber learning. Both normal and stimulated rats demonstrated improved performance in novel object recognition and auditory learning as compared to the unstimulated SAP group. The burst stimulation groups performed better than the tonic group. Increasing the daily stimulation duration to 24 hr did not further improve cognitive performance in an auditory recognition task and degraded the results on a novel object recognition task as compared with 5 hr. The present findings suggest that naturalistic NBM burst DBS may offer potential effective therapy for treating dementia and suggests potential strategies for the reevaluation of current human NBM stimulation paradigms. (PsycInfo Database Record (c) 2025 APA, all rights reserved).

摘要

作为痴呆症的一种潜在治疗方法,已对内侧缰核(NBM)进行了深部脑刺激(DBS)的初步研究。NBM胆碱能神经元的退化是多种形式痴呆症的病理特征。尽管已证明NBM刺激可改善学习能力,但NBM刺激的理想参数尚未阐明。本研究评估了不同刺激模式和持续时间对患有胆碱能缺陷的痴呆大鼠模型学习能力的差异影响。将192-IgG皂草素(SAP)或杜氏磷酸盐缓冲盐水注入NBM以在大鼠中诱发痴呆。接下来,所有大鼠均在NBM中进行单侧DBS电极植入。实验组包括:(a)正常组,(b)未治疗的注射SAP且有胆碱能缺陷的大鼠,以及(c)接受NBM DBS的SAP大鼠。刺激范式包括在10个每日疗程中测试不同模式(强直和爆发)和持续时间(每天1小时、5小时和24小时)。使用两种既定的学习范式评估记忆:新物体识别和听觉操作性条件学习。与未刺激的SAP组相比,正常组和刺激组在新物体识别和听觉学习方面均表现出更好的成绩。爆发刺激组的表现优于强直刺激组。与5小时相比,将每日刺激持续时间增加到24小时并未在听觉识别任务中进一步改善认知表现,反而使新物体识别任务的结果变差。目前的研究结果表明,自然主义的NBM爆发性DBS可能为治疗痴呆症提供潜在的有效疗法,并为重新评估当前人类NBM刺激范式提供了潜在策略。(PsycInfo数据库记录(c)2025美国心理学会,保留所有权利)

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