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mTOR Knockdown in the Infralimbic Cortex Evokes A Depressive-like State in Mouse

Centro de Investigación Biomédica en Red de Salud Mental (CIBERSAM), Instituto de Salud Carlos III, 28029 Madrid, Spain
Instituto de Biomedicina y Biotecnología de Cantabria (IBBTEC), Universidad de Cantabria-CSIC-SODERCAN, 39011 Santander, Spain
Departamento de Fisiología y Farmacología, Universidad de Cantabria, 39011 Santander, Spain
Department of Neuroscience and Experimental Therapeutics, Instituto de Investigaciones Biomédicas de Barcelona (IIBB-CSIC), 08036 Barcelona, Spain
Systems Neuropharmacology Group, Instituto de Investigaciones Biomédicas August Pi i Sunyer (IDIBAPS), 08036 Barcelona, Spain
Author to whom correspondence should be addressed.
Present address: Emilio Garro-Martínez, Department of Integrative Medical Biology (IMB), Umeå Universitet, 901 87 Umeå, Sweden.
Academic Editor: Masaru Tanaka
Int. J. Mol. Sci. 2021, 22(16), 8671;
Received: 14 July 2021 / Revised: 8 August 2021 / Accepted: 9 August 2021 / Published: 12 August 2021
Fast and sustained antidepressant effects of ketamine identified the mammalian target of rapamycin (mTOR) signaling pathway as the main modulator of its antidepressive effects. Thus, mTOR signaling has become integral for the preclinical evaluation of novel compounds to treat depression. However, causality between mTOR and depression has yet to be determined. To address this, we knocked down mTOR expression in mice using an acute intracerebral infusion of small interfering RNAs (siRNA) in the infralimbic (IL) or prelimbic (PrL) cortices of the medial prefrontal cortex (mPFC), and evaluated depressive- and anxious-like behaviors. mTOR knockdown in IL, but not PrL, cortex produced a robust depressive-like phenotype in mice, as assessed in the forced swimming test (FST) and the tail suspension test (TST). This phenotype was associated with significant reductions of mTOR mRNA and protein levels 48 h post-infusion. In parallel, decreased brain-derived neurotrophic factor (BDNF) expression was found bilaterally in both IL and PrL cortices along with a dysregulation of serotonin (5-HT) and glutamate (Glu) release in the dorsal raphe nucleus (DRN). Overall, our results demonstrate causality between mTOR expression in the IL cortex and depressive-like behaviors, but not in anxiety. View Full-Text
Keywords: mTOR; infralimbic cortex; behavioral despair; BDNF; neurotransmitter mTOR; infralimbic cortex; behavioral despair; BDNF; neurotransmitter
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MDPI and ACS Style

Garro-Martínez, E.; Fullana, M.N.; Florensa-Zanuy, E.; Senserrich, J.; Paz, V.; Ruiz-Bronchal, E.; Adell, A.; Castro, E.; Díaz, Á.; Pazos, Á.; Bortolozzi, A.; Pilar-Cuéllar, F. mTOR Knockdown in the Infralimbic Cortex Evokes A Depressive-like State in Mouse. Int. J. Mol. Sci. 2021, 22, 8671.

AMA Style

Garro-Martínez E, Fullana MN, Florensa-Zanuy E, Senserrich J, Paz V, Ruiz-Bronchal E, Adell A, Castro E, Díaz Á, Pazos Á, Bortolozzi A, Pilar-Cuéllar F. mTOR Knockdown in the Infralimbic Cortex Evokes A Depressive-like State in Mouse. International Journal of Molecular Sciences. 2021; 22(16):8671.

Chicago/Turabian Style

Garro-Martínez, Emilio, Maria Neus Fullana, Eva Florensa-Zanuy, Julia Senserrich, Verónica Paz, Esther Ruiz-Bronchal, Albert Adell, Elena Castro, Álvaro Díaz, Ángel Pazos, Analía Bortolozzi, and Fuencisla Pilar-Cuéllar. 2021. "mTOR Knockdown in the Infralimbic Cortex Evokes A Depressive-like State in Mouse" International Journal of Molecular Sciences 22, no. 16: 8671.

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