Intracranial self-stimulation reverses impaired spatial learning and regulates serum microRNA levels in a streptozotocin-induced rat model of Alzheimer disease
Riberas-Sánchez, Andrea (Universitat de Girona)
Puig-Parnau, Irene (Universitat de Girona)
Vila-Solés, Laia (Universitat Autònoma de Barcelona. Departament de Psicobiologia i de Metodologia de les Ciències de la Salut)
García-Brito, Soleil (Universitat Autònoma de Barcelona. Departament de Psicobiologia i de Metodologia de les Ciències de la Salut)
Aldavert Vera, Laura (Universitat Autònoma de Barcelona. Departament de Psicobiologia i de Metodologia de les Ciències de la Salut)
Segura Torres, Pilar (Universitat Autònoma de Barcelona. Departament de Psicobiologia i de Metodologia de les Ciències de la Salut)
Huguet, Gemma (Universitat de Girona)
Kádár, Elisabet (Universitat de Girona)
Universitat Autònoma de Barcelona. Institut de Neurociències

Data:	2024
Descripció:	13 pàg.
Resum:	Background: The assessment of deep brain stimulation (DBS) as a therapeutic alternative for treating Alzheimer disease (AD) is on-going. 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 with-out 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.
Ajuts:	Agencia Estatal de Investigación PID2020-117101RB-C21 Agencia Estatal de Investigación PID2020-117101RB-C22
Nota:	Altres ajuts: Universitat de Girona (IFUdG2022/63)
Drets:	Aquest document està subjecte a una llicència d'ús Creative Commons. Es permet la reproducció total o parcial, la distribució, i la comunicació pública de l'obra, sempre que no sigui amb finalitats comercials, i sempre que es reconegui l'autoria de l'obra original. No es permet la creació d'obres derivades.
Llengua:	Anglès
Document:	Article ; recerca ; Versió publicada
Publicat a:	Journal of psychiatry & neuroscience, Vol. 49 Núm. 2 (march 2024) , p. E96-E108, ISSN 1488-2434

DOI: 10.1503/jpn.230066
PMID: 38490646

13 p, 3.0 MB

El registre apareix a les col·leccions:
Documents de recerca > Documents dels grups de recerca de la UAB > Centres i grups de recerca (producció científica) > Ciències de la salut i biociències > Institut de Neurociències (INc)
Articles > Articles de recerca
Articles > Articles publicats