Chronic Inhibition of FAAH Reduces Depressive-Like Behavior and Improves Dentate Gyrus Proliferation after Chronic Unpredictable Stress Exposure
Symptoms of depressive disorders such as anhedonia and despair can be a product of an aberrant adaptation to stress conditions. Chronic unpredictable stress model (CUS) can generate an increase in the activity of the hypothalamic-pituitary-adrenal axis (HPA) and induce a reduction of neurotrophin si...
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| Format: | Article |
| Language: | English |
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Wiley
2021-01-01
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| Series: | Behavioural Neurology |
| Online Access: | http://dx.doi.org/10.1155/2021/6651492 |
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| author | A. R. Tejeda-Martínez J. M. Viveros-Paredes G. V. Hidalgo-Franco E. Pardo-González V. Chaparro-Huerta R. E. González-Castañeda M. E. Flores-Soto |
| author_facet | A. R. Tejeda-Martínez J. M. Viveros-Paredes G. V. Hidalgo-Franco E. Pardo-González V. Chaparro-Huerta R. E. González-Castañeda M. E. Flores-Soto |
| author_sort | A. R. Tejeda-Martínez |
| collection | DOAJ |
| description | Symptoms of depressive disorders such as anhedonia and despair can be a product of an aberrant adaptation to stress conditions. Chronic unpredictable stress model (CUS) can generate an increase in the activity of the hypothalamic-pituitary-adrenal axis (HPA) and induce a reduction of neurotrophin signaling and the proliferation of neural progenitors in the adult dentate gyrus, together with increased oxidative stress. Levels of the endocannabinoid anandamide (AEA) seem to affect these depression-by-stress-related features and could be modulated by fatty acid amide hydrolase (FAAH). We aimed to evaluate the effects of FAAH inhibitor, URB597, on depressive-like behavior and neural proliferation of mice subjected to a model of CUS. URB597 was administered intraperitoneally at a dose of 0.2 mg/kg for 14 days after CUS. Depressive-like behaviors, anhedonia, and despair were evaluated in the splash and forced swimming tests, respectively. Alterations at the HPA axis level were analyzed using the relative weight of adrenal glands and serum corticosterone levels. Oxidative stress and brain-derived neurotrophic factor (BDNF) were also evaluated. Fluorescence immunohistochemistry tests were performed for the immunoreactivity of BrdU and Sox2 colabeling for comparison of neural precursors. The administration of URB597 was able to reverse the depressive-like behavior generated in mice after the model. Likewise, other physiological responses associated with CUS were reduced in the treated group, among them, increase in the relative weight of the adrenal glands, increased oxidative stress, and decreased BDNF and number of neural precursors. Most of these auspicious responses to enzyme inhibitor administration were blocked by employing a cannabinoid receptor antagonist. In conclusion, the chronic inhibition of FAAH generated an antidepressant effect, promoting neural progenitor proliferation and BDNF expression, while reducing adrenal gland weight and oxidative stress in mice under the CUS model. |
| format | Article |
| id | doaj-art-658b4d4cddc04a44b3380c9fe33d3817 |
| institution | Kabale University |
| issn | 0953-4180 1875-8584 |
| language | English |
| publishDate | 2021-01-01 |
| publisher | Wiley |
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| series | Behavioural Neurology |
| spelling | doaj-art-658b4d4cddc04a44b3380c9fe33d38172025-02-03T05:58:30ZengWileyBehavioural Neurology0953-41801875-85842021-01-01202110.1155/2021/66514926651492Chronic Inhibition of FAAH Reduces Depressive-Like Behavior and Improves Dentate Gyrus Proliferation after Chronic Unpredictable Stress ExposureA. R. Tejeda-Martínez0J. M. Viveros-Paredes1G. V. Hidalgo-Franco2E. Pardo-González3V. Chaparro-Huerta4R. E. González-Castañeda5M. E. Flores-Soto6Laboratorio de Neurobiología Celular y Molecular, División de Neurociencias, Centro de Investigación Biomédica de Occidente (CIBO), Instituto Mexicano del Seguro Social, 44340, MexicoLaboratorio de Investigación y Desarrollo Farmacéutico, Departamento de Farmacología, Centro Universitario de Ciencias Exactas e Ingenierías, Universidad de Guadalajara, 44430, MexicoLaboratorio de Neurobiología Celular y Molecular, División de Neurociencias, Centro de Investigación Biomédica de Occidente (CIBO), Instituto Mexicano del Seguro Social, 44340, MexicoLaboratorio de Neurobiología Celular y Molecular, División de Neurociencias, Centro de Investigación Biomédica de Occidente (CIBO), Instituto Mexicano del Seguro Social, 44340, MexicoLaboratorio de Neurobiología Celular y Molecular, División de Neurociencias, Centro de Investigación Biomédica de Occidente (CIBO), Instituto Mexicano del Seguro Social, 44340, MexicoLaboratorio de Microscopia de alta resolución, Departamento de Neurociencias, Centro Universitario de Ciencias de la Salud, Universidad de Guadalajara, 44340, MexicoLaboratorio de Neurobiología Celular y Molecular, División de Neurociencias, Centro de Investigación Biomédica de Occidente (CIBO), Instituto Mexicano del Seguro Social, 44340, MexicoSymptoms of depressive disorders such as anhedonia and despair can be a product of an aberrant adaptation to stress conditions. Chronic unpredictable stress model (CUS) can generate an increase in the activity of the hypothalamic-pituitary-adrenal axis (HPA) and induce a reduction of neurotrophin signaling and the proliferation of neural progenitors in the adult dentate gyrus, together with increased oxidative stress. Levels of the endocannabinoid anandamide (AEA) seem to affect these depression-by-stress-related features and could be modulated by fatty acid amide hydrolase (FAAH). We aimed to evaluate the effects of FAAH inhibitor, URB597, on depressive-like behavior and neural proliferation of mice subjected to a model of CUS. URB597 was administered intraperitoneally at a dose of 0.2 mg/kg for 14 days after CUS. Depressive-like behaviors, anhedonia, and despair were evaluated in the splash and forced swimming tests, respectively. Alterations at the HPA axis level were analyzed using the relative weight of adrenal glands and serum corticosterone levels. Oxidative stress and brain-derived neurotrophic factor (BDNF) were also evaluated. Fluorescence immunohistochemistry tests were performed for the immunoreactivity of BrdU and Sox2 colabeling for comparison of neural precursors. The administration of URB597 was able to reverse the depressive-like behavior generated in mice after the model. Likewise, other physiological responses associated with CUS were reduced in the treated group, among them, increase in the relative weight of the adrenal glands, increased oxidative stress, and decreased BDNF and number of neural precursors. Most of these auspicious responses to enzyme inhibitor administration were blocked by employing a cannabinoid receptor antagonist. In conclusion, the chronic inhibition of FAAH generated an antidepressant effect, promoting neural progenitor proliferation and BDNF expression, while reducing adrenal gland weight and oxidative stress in mice under the CUS model.http://dx.doi.org/10.1155/2021/6651492 |
| spellingShingle | A. R. Tejeda-Martínez J. M. Viveros-Paredes G. V. Hidalgo-Franco E. Pardo-González V. Chaparro-Huerta R. E. González-Castañeda M. E. Flores-Soto Chronic Inhibition of FAAH Reduces Depressive-Like Behavior and Improves Dentate Gyrus Proliferation after Chronic Unpredictable Stress Exposure Behavioural Neurology |
| title | Chronic Inhibition of FAAH Reduces Depressive-Like Behavior and Improves Dentate Gyrus Proliferation after Chronic Unpredictable Stress Exposure |
| title_full | Chronic Inhibition of FAAH Reduces Depressive-Like Behavior and Improves Dentate Gyrus Proliferation after Chronic Unpredictable Stress Exposure |
| title_fullStr | Chronic Inhibition of FAAH Reduces Depressive-Like Behavior and Improves Dentate Gyrus Proliferation after Chronic Unpredictable Stress Exposure |
| title_full_unstemmed | Chronic Inhibition of FAAH Reduces Depressive-Like Behavior and Improves Dentate Gyrus Proliferation after Chronic Unpredictable Stress Exposure |
| title_short | Chronic Inhibition of FAAH Reduces Depressive-Like Behavior and Improves Dentate Gyrus Proliferation after Chronic Unpredictable Stress Exposure |
| title_sort | chronic inhibition of faah reduces depressive like behavior and improves dentate gyrus proliferation after chronic unpredictable stress exposure |
| url | http://dx.doi.org/10.1155/2021/6651492 |
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