Intracranial Self-Stimulation Modulates Levels of SIRT1 Protein and Neural Plasticity-Related microRNAs

Area of Science:

• Neuroscience
• Molecular Biology
• Biochemistry

Background:

• Deep brain stimulation (DBS) of reward pathways, like the medial forebrain bundle (MFB), enhances learning and memory in rodents via intracranial self-stimulation (ICSS).
• MFB-ICSS influences plasticity-related proteins, but its molecular mechanisms, particularly involving microRNAs (miRNAs) and SIRT1, require further investigation.
• miRNAs and SIRT1 are crucial regulatory molecules in neural plasticity and memory formation.

Purpose of the Study:

• To investigate the effects of MFB-ICSS on miRNA expression and SIRT1 protein levels in specific hippocampal subfields (dentate gyrus, CA1, CA3) and serum.
• To explore the potential role of these molecular changes in mediating the memory-enhancing effects of MFB-ICSS.

Main Methods:

• Rats underwent MFB-ICSS or sham procedures.
• OpenArray was used to identify differentially expressed miRNAs in the dentate gyrus (DG).
• Quantitative real-time PCR (qRT-PCR) analyzed selected miRNAs (including miR-132-3p, miR-181c-5p, miR-495-3p) in DG, CA1, CA3, and serum.
• Western Blot and ELISA measured SIRT1 protein levels in tissue and serum, respectively.

Main Results:

• MFB-ICSS significantly upregulated miR-132-3p, miR-181c-5p, miR-495-3p, and SIRT1 protein in the DG.
• miR-132-3p levels were also elevated in the CA1 subfield and serum of ICSS-treated rats.
• No significant changes in the analyzed molecules were observed in the CA3 subfield.

Conclusions:

• MFB-ICSS modulates specific plasticity-related miRNAs and SIRT1 protein levels within distinct hippocampal subfields.
• These molecular changes are proposed as key mechanisms underlying MFB-ICSS-induced memory improvement.
• Serum miR-132 emerges as a potential biomarker for monitoring DBS treatment efficacy, given its clinical applicability.