Inhibition of Adult Neurogenesis in Male Mice after Repeated Exposure to Paracetamol Overdose
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Published:2024-02-06
Issue:4
Volume:25
Page:1964
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ISSN:1422-0067
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Container-title:International Journal of Molecular Sciences
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language:en
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Short-container-title:IJMS
Author:
Suárez Juan12ORCID, de Ceglia Marialuisa2ORCID, Rodríguez-Pozo Miguel12ORCID, Vargas Antonio2, Santos Ignacio1, Melgar-Locatelli Sonia23, Castro-Zavala Adriana23ORCID, Castilla-Ortega Estela23ORCID, Rodríguez de Fonseca Fernando24ORCID, Decara Juan2ORCID, Rivera Patricia2
Affiliation:
1. Departamento de Anatomía Humana, Medicina Legal e Historia de la Ciencia, Facultad de Medicina, Universidad de Málaga, 29071 Málaga, Spain 2. Grupo de Neuropsicofarmacología, Instituto IBIMA-Plataforma BIONAND, Unidad de Gestión Clínica de Salud Mental, Hospital Regional Universitario de Málaga, Av. de Carlos Haya, 29010 Málaga, Spain 3. Departamento de Psicobiología y Metodología de las Ciencias del Comportamiento, Facultad de Psicología, Universidad de Málaga, 29010 Málaga, Spain 4. Unidad Clínica de Neurología, Hospital Regional Universitario de Málaga, Instituto IBMA-Plataforma BIONAND, 29010 Málaga, Spain
Abstract
Paracetamol, or acetaminophen (N-acetyl-para-aminophenol, APAP), is an analgesic and antipyretic drug that is commonly used worldwide, implicated in numerous intoxications due to overdose, and causes serious liver damage. APAP can cross the blood–brain barrier and affects brain function in numerous ways, including pain signals, temperature regulation, neuroimmune response, and emotional behavior; however, its effect on adult neurogenesis has not been thoroughly investigated. We analyze, in a mouse model of hepatotoxicity, the effect of APAP overdose (750 mg/kg/day) for 3 and 4 consecutive days and after the cessation of APAP administration for 6 and 15 days on cell proliferation and survival in two relevant neurogenic zones: the subgranular zone of the dentate gyrus and the hypothalamus. The involvement of liver damage (plasma transaminases), neuronal activity (c-Fos), and astroglia (glial fibrillar acidic protein, GFAP) were also evaluated. Our results indicated that repeated APAP overdoses are associated with the inhibition of adult neurogenesis in the context of elevated liver transaminase levels, neuronal hyperactivity, and astrogliosis. These effects were partially reversed after the cessation of APAP administration for 6 and 15 days. In conclusion, these results suggest that APAP overdose impairs adult neurogenesis in the hippocampus and hypothalamus, a fact that may contribute to the effects of APAP on brain function.
Funder
Consejería de Salud, Junta de Andalucía, ERDF-EU Consejería de Universidad, Investigación e Innovación “Miguel Servet” European Social Fund, “Investing in your future”, Gobierno de España
Subject
Inorganic Chemistry,Organic Chemistry,Physical and Theoretical Chemistry,Computer Science Applications,Spectroscopy,Molecular Biology,General Medicine,Catalysis
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