Details

Autor(en) / Beteiligte

• Puig-Parnau, Irene
• Garcia-Brito, Soleil
• Faghihi, Nastaran
• Gubern, Carme
• Aldavert-Vera, Laura
• Segura-Torres, Pilar
• Huguet, Gemma
• Kádár, Elisabet

Titel

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

Ist Teil von

• Molecular neurobiology, 2020-06, Vol.57 (6), p.2551-2562

Ort / Verlag

New York: Springer US

Erscheinungsjahr

2020

Quelle

MEDLINE

Beschreibungen/Notizen

• Deep brain stimulation (DBS) of reward system brain areas, such as the medial forebrain bundle (MFB), by means of intracranial self-stimulation (ICSS), facilitates learning and memory in rodents. MFB-ICSS has been found capable of modifying different plasticity-related proteins, but its underlying molecular mechanisms require further elucidation. MicroRNAs (miRNAs) and the longevity-associated SIRT1 protein have emerged as important regulatory molecules implicated in neural plasticity. Thus, we aimed to analyze the effects of MFB-ICSS on miRNAs expression and SIRT1 protein levels in hippocampal subfields and serum. We used OpenArray to select miRNA candidates differentially expressed in the dentate gyrus (DG) of ICSS-treated (3 sessions, 45′ session/day) and sham rats. We further analyzed the expression of these miRNAs, together with candidates selected after bibliographic screening (miR-132-3p, miR-134-5p, miR-146a-5p, miR-181c-5p) in DG, CA1, and CA3, as well as in serum, by qRT-PCR. We also assessed tissue and serum SIRT1 protein levels by Western Blot and ELISA, respectively. Expression of miR-132-3p, miR-181c-5p, miR-495-3p, and SIRT1 protein was upregulated in DG of ICSS rats ( P  < 0.05). None of the analyzed molecules was regulated in CA3, while miR-132-3p was also increased in CA1 ( P  = 0.011) and serum ( P  = 0.048). This work shows for the first time that a DBS procedure, specifically MFB-ICSS, modulates the levels of plasticity-related miRNAs and SIRT1 in specific hippocampal subfields. The mechanistic role of these molecules could be key to the improvement of memory by MFB-ICSS. Moreover, regarding the proposed clinical applicability of DBS, serum miR-132 is suggested as a potential treatment biomarker.