Preprint Article Version 1 Preserved in Portico This version is not peer-reviewed

Inhibition of Adult Neurogenesis in Male Mice after Repeated Exposure to Paracetamol Overdose

Juan Suarez
ORCID logo ,
Marialuisa De Ceglia
ORCID logo ,
Miguel Rodríguez-Pozo
ORCID logo ,
Antonio Vargas
,
Ignacio Santos
,
Sonia Melgar-Locatelli
,
Adriana Castro-Zavala
,
Estela Castilla-Ortega
ORCID logo ,
Fernando Rodríguez de Fonseca
ORCID logo ,
Juan Decara
* ORCID logo ,
Patricia Rivera
*
Version 1 : Received: 23 December 2023 / Approved: 25 December 2023 / Online: 25 December 2023 (11:24:16 CET)

A peer-reviewed article of this Preprint also exists.

Suárez, J.; de Ceglia, M.; Rodríguez-Pozo, M.; Vargas, A.; Santos, I.; Melgar-Locatelli, S.; Castro-Zavala, A.; Castilla-Ortega, E.; Rodríguez de Fonseca, F.; Decara, J.; Rivera, P. Inhibition of Adult Neurogenesis in Male Mice after Repeated Exposure to Paracetamol Overdose. Int. J. Mol. Sci. 2024, 25, 1964. Suárez, J.; de Ceglia, M.; Rodríguez-Pozo, M.; Vargas, A.; Santos, I.; Melgar-Locatelli, S.; Castro-Zavala, A.; Castilla-Ortega, E.; Rodríguez de Fonseca, F.; Decara, J.; Rivera, P. Inhibition of Adult Neurogenesis in Male Mice after Repeated Exposure to Paracetamol Overdose. Int. J. Mol. Sci. 2024, 25, 1964.

Abstract

Paracetamol or acetaminophen (N-acetyl-para-aminophenol, APAP) is an analgesic and antipy-retic drug commonly used worldwide, implicated in numerous intoxications due to overdose, and causing 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 investi-gated. We analyze the effect of APAP overdose (750 mg/kg/day), for 3 and 4 consecutive days and after 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 (GFAP) was also evaluated. Our results indicated that repeated APAP overdoses were associated with inhibition of adult neurogenesis in a context of elevated liver transaminase levels, neuronal hyperactivity and as-trogliosis. These effects were partially reversed after cessation of APAP administration for 6 and 15 days. In conclusion, these results suggest that APAP overdose impairs adult neurogenesis in the hip-pocampus and hypothalamus, a fact that may contribute to the effects of APAP on brain function.

Keywords

adult neurogenesis; acetaminophen; paracetamol; endocannabinoid; subgranular zone; hypo-thalamus; toxicology

Subject

Medicine and Pharmacology, Neuroscience and Neurology

Copyright: This is an open access article distributed under the Creative Commons Attribution License which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

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