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.
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Deep brain stimulation
Medial forebrain bundle
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The authors thank Dr. Anna Mercader Carceller for her technical support. Likewise, we thank Carlos Baldellou Estrada and Cristina Gerboles Freixas for their inestimable technical contribution.
Ministerio de Economía, Indústria y Competitividad (MINECO) provided financial support for the conduct of this work (grant number PSI2017-83202-C2-2-P). I. Puig-Parnau is a recipient of a predoctoral fellowship from the University of Girona (grant number IFUdG2017/61).
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The authors declare that they have no conflict of interest.
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Puig-Parnau, I., Garcia-Brito, S., Faghihi, N. et al. Intracranial Self-Stimulation Modulates Levels of SIRT1 Protein and Neural Plasticity-Related microRNAs. Mol Neurobiol 57, 2551–2562 (2020). https://doi.org/10.1007/s12035-020-01901-w
- Intracranial self-stimulation
- Neural plasticity