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Obesity-dependent cannabinoid modulation of proliferation in adult neurogenic regions

Authors

  • Patricia Rivera,

    1. Laboratorio de Medicina Regenerativa, Hospital Carlos Haya, Fundación IMABIS, Avda. Carlos Haya 82, Pabellón de Gobierno, 29010, Málaga, Spain
    2. CIBER OBN, Instituto de Salud Carlos III, Ministerio de Ciencia e Innovación, Madrid, Spain
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  • Yanina Romero-Zerbo,

    1. Laboratorio de Medicina Regenerativa, Hospital Carlos Haya, Fundación IMABIS, Avda. Carlos Haya 82, Pabellón de Gobierno, 29010, Málaga, Spain
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  • Francisco J. Pavón,

    1. Laboratorio de Medicina Regenerativa, Hospital Carlos Haya, Fundación IMABIS, Avda. Carlos Haya 82, Pabellón de Gobierno, 29010, Málaga, Spain
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  • Antonia Serrano,

    1. Laboratorio de Medicina Regenerativa, Hospital Carlos Haya, Fundación IMABIS, Avda. Carlos Haya 82, Pabellón de Gobierno, 29010, Málaga, Spain
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  • María-Dolores López-Ávalos,

    1. Departamento de Biología Celular, Genética y Fisiología, Facultad de Ciencias, Universidad de Málaga, 29071, Málaga, Spain
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  • Manuel Cifuentes,

    1. Departamento de Biología Celular, Genética y Fisiología, Facultad de Ciencias, Universidad de Málaga, 29071, Málaga, Spain
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  • Jesús-Mateos Grondona,

    1. Departamento de Biología Celular, Genética y Fisiología, Facultad de Ciencias, Universidad de Málaga, 29071, Málaga, Spain
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  • Francisco-Javier Bermúdez-Silva,

    1. Laboratorio de Medicina Regenerativa, Hospital Carlos Haya, Fundación IMABIS, Avda. Carlos Haya 82, Pabellón de Gobierno, 29010, Málaga, Spain
    2. CIBER OBN, Instituto de Salud Carlos III, Ministerio de Ciencia e Innovación, Madrid, Spain
    3. Neurocentre Magendie, Inserm U862, Bordeaux, France
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  • Pedro Fernández-Llebrez,

    1. Departamento de Biología Celular, Genética y Fisiología, Facultad de Ciencias, Universidad de Málaga, 29071, Málaga, Spain
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  • Fernando R. de Fonseca,

    1. Laboratorio de Medicina Regenerativa, Hospital Carlos Haya, Fundación IMABIS, Avda. Carlos Haya 82, Pabellón de Gobierno, 29010, Málaga, Spain
    2. CIBER OBN, Instituto de Salud Carlos III, Ministerio de Ciencia e Innovación, Madrid, Spain
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  • Juan Suárez,

    1. Laboratorio de Medicina Regenerativa, Hospital Carlos Haya, Fundación IMABIS, Avda. Carlos Haya 82, Pabellón de Gobierno, 29010, Málaga, Spain
    2. CIBER OBN, Instituto de Salud Carlos III, Ministerio de Ciencia e Innovación, Madrid, Spain
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  • Margarita Pérez-Martín

    1. Departamento de Biología Celular, Genética y Fisiología, Facultad de Ciencias, Universidad de Málaga, 29071, Málaga, Spain
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Dr J. Suárez, 1Fundación IMABIS, as above.
E-mail: juan.suarez@fundacionimabis.orgDr. M. Pérez-Martín, 3Departamento de Biología Celular, as above.
E-mail: marper@uma.es

Abstract

Endocannabinoid signalling participates in the control of neurogenesis, especially after brain insults. Obesity may explain alterations in physiology affecting neurogenesis, although it is unclear whether cannabinoid signalling may modulate neural proliferation in obese animals. Here we analyse the impact of obesity by using two approaches, a high-fat diet (HFD, 60% fat) and a standard/low-fat diet (STD, 10% fat), and the response to a subchronic treatment with the cannabinoid receptor type 1 (CB1) inverse agonist AM251 (3 mg/kg) on cell proliferation of two relevant neurogenic regions, namely the subventricular zone in the striatal wall of the lateral ventricle (SVZ) and the subgranular zone of the dentate gyrus (SGZ), and also in the hypothalamus given its role in energy metabolism. We found evidence of an interaction between diet-induced obesity and CB1 signalling in the regulation of cell proliferation. AM251 reduced caloric intake and body weight in obese rats, as well as corrected plasma levels of cholesterol and triglycerides. AM251 is shown, for the first time, to modulate cell proliferation in HFD-obese rats only. We observed an increase in the number of 5-bromo-2-deoxyuridine-labelled (BrdU+) cells in the SGZ, but a decrease in the number of BrdU+ cells in the SVZ and the hypothalamus of AM251-treated HFD rats. These BrdU+ cells expressed the neuron-specific βIII-tubulin. These results suggest that obesity may impact cell proliferation in the brain selectively, and provide support for a role of CB1 signalling regulation of neurogenesis in response to obesity.

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