Intracranial Self-stimulation Reverses Impaired Spatial Learning and Regulates Serum MicroRNA Levels in a Streptozotocin-induced Rat Model of Alzheimer Disease

Overview

Journal J Psychiatry Neurosci

Specialty Psychiatry

Date 2024 Mar 15

PMID 38490646

Authors

Andrea Riberas-Sanchez

Irene Puig-Parnau

Laia Vila-Soles

Soleil Garcia-Brito

Laura Aldavert-Vera

Pilar Segura-Torres

Gemma Huguet

Elisabet Kadar

Affiliations

Soon will be listed here.

Abstract

Background: The assessment of deep brain stimulation (DBS) as a therapeutic alternative for treating Alzheimer disease (AD) is ongoing. We aimed to determine the effects of intracranial self-stimulation at the medial forebrain bundle (MFB-ICSS) on spatial memory, neurodegeneration, and serum expression of microRNAs (miRNAs) in a rat model of sporadic AD created by injection of streptozotocin. We hypothesized that MFB-ICSS would reverse the behavioural effects of streptozotocin and modulate hippocampal neuronal density and serum levels of the miRNAs.

Methods: We performed Morris water maze and light-dark transition tests. Levels of various proteins, specifically amyloid-β precurser protein (APP), phosphorylated tau protein (pTAU), and sirtuin 1 (SIRT1), and neurodegeneration were analyzed by Western blot and Nissl staining, respectively. Serum miRNA expression was measured by reverse transcription polymerase chain reaction.

Results: Male rats that received streptozotocin had increased hippocampal levels of pTAU S202/T205, APP, and SIRT1 proteins; increased neurodegeneration in the CA1, dentate gyrus (DG), and dorsal tenia tecta; and worse performance in the Morris water maze task. No differences were observed in miRNAs, except for miR-181c and miR-let-7b. After MFB-ICSS, neuronal density in the CA1 and DG regions and levels of miR-181c in streptozotocin-treated and control rats were similar. Rats that received streptozotocin and underwent MFB-ICSS also showed lower levels of miR-let-7b and better spatial learning than rats that received streptozotocin without MFB-ICSS.

Limitations: The reversal by MFB-ICSS of deficits induced by streptozotocin was fairly modest.

Conclusion: Spatial memory performance, hippocampal neurodegeneration, and serum levels of miR-let-7b and miR-181c were affected by MFB-ICSS under AD-like conditions. Our results validate the MFB as a potential target for DBS and lend support to the use of specific miRNAs as promising biomarkers of the effectiveness of DBS in combatting AD-associated cognitive deficits.

Citing Articles

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PMID: 39386180 PMC: 11461251. DOI: 10.3389/fncel.2024.1432359.

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