Intracranial Self-stimulation of the Medial Forebrain Bundle Ameliorates Memory Disturbances and Pathological Hallmarks in an Alzheimer's Disease Model by Intracerebral Administration of Amyloid-β in Rats

curative or fully effective treatments are currently available for Alzheimer's disease (AD), the most common form of dementia. Electrical stimulation of deep brain areas has been proposed as a novel neuromodu-latory therapeutic approach. Previous research from our lab demonstrates that intracranial self-stimulation (ICSS) targeting medial forebrain bundle (MFB) facilitates explicit and implicit learning and memory in rats with age or lesion-related memory impairment. At a molecular level, MFB-ICSS modulates the expression of plasticity and neuroprotection-related genes in memory-related brain areas. On this basis, we suggest that MFB could be a promising stimulation target for AD treatment. In this study, we aimed to assess the effects of MFB-ICSS on both explicit memory as well as the levels of neuropathological markers ptau and drebrin (DBN) in memory-related areas, in an AD rat model obtained by Ab icv-injection. A total of 36 male rats were trained in the Morris water maze on days 26-30 after Ab injection and tested on day 33. Results demonstrate that this Ab model displayed spatial memory impairment in the retention test, accompanied by changes in the levels of DBN and ptau in lateral entorhi-nal cortex and hippocampus, resembling pathological alterations in early AD. Administration of MFB-ICSS treat-ment consisting of 5 post-training sessions to AD rats managed to reverse the memory deficits as well as the alteration in ptau and DBN levels. Thus, this paper reports both cognitive and molecular effects of a post -training reinforcing deep brain stimulation procedure in a sporadic AD model for the first time.(c) 2023 The Author (s). Published by Elsevier Ltd on behalf of IBRO. This is an open access article under the CC BY-NC-ND license (http://creativecom-mons.org/licenses/by-nc-nd/4.0/).

Automated summary

Curative or fully effective treatments for Alzheimer's disease (AD) are currently unavailable. Electrical stimulation of deep brain areas is proposed as a therapeutic approach. Previous research shows that intracranial self-stimulation (ICSS) targeting the medial forebrain bundle (MFB) improves learning and memory in rats with memory impairment. Based on this, MFB could be a promising target for AD treatment.