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Prenatal Methamphetamine Hydrochloride Exposure Leads to Signal Transduction Alteration and Cell Death in the Prefrontal Cortex and Amygdala of Male and Female Rats’ Offspring

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Abstract

In the last decade, there has been a great increase in methamphetamine hydrochloride (METH) abuse by pregnant women that exposes fetus and human offspring to a wide variety of developmental impairments that may be the underlying causes of future psychosocial issues. Herein, we investigated whether prenatal METH exposure with different doses (2 and 5 mg/kg) could influence neuronal cell death and antioxidant level in the different brain regions of adult male and female offspring. Adult male and female Wistar rats prenatally exposed to METH (2 or 5 mg/kg) and/or saline was used in this study. At week 12, adult rats’ offspring were decapitated to collect different brain region tissues including amygdala (AMY) and prefrontal cortices (PFC). Western blot analysis was performed to evaluate the apoptosis- and autophagy-related markers, and enzymatic assay was used to measure the level of catalase and also reduced glutathione (GSH). Our results showed that METH exposure during pregnancy increased the level of apoptosis (BAX/Bcl-2 and Caspase-3) and autophagy (Beclin-1 and LC3II/LC3I) in the PFC and AMY areas of both male and female offspring’s brain. Also, we found an elevation in the GSH content of all both mentioned brain areas and catalase activity of PFC in the offspring’s brain. These changes were more significant in female offspring. Being prenatally exposed to METH increased cell death at least partly via apoptosis and autophagy in AMY and PFC of male and female offspring’s brain, while the antioxidant system tried to protect cells in these regions.

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Funding

This work was supported by the research grant of Shahid Beheshti University of Medical Sciences (No. 13422–8-2).

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  1. Nayereh Zare and Nader Maghsoudi contributed equally to this work.

Authors and Affiliations

  1. Department of Anatomical Sciences and Cognitive Neuroscience, Faculty of Medicine, Tehran Medical Sciences, Islamic Azad University, Tehran, Iran

    Nayereh Zare

  2. Neurobiology Research Center, Shahid Beheshti University of Medical Sciences, Tehran, Iran

    Nader Maghsoudi, Seyed Hamidreza Mirbehbahani & Zahra Mansouri

  3. Neuroscience Research Center, Shahid Beheshti University of Medical Sciences, Tehran, Iran

    Seyed Hamidreza Mirbehbahani, Zahra Mansouri & Fariba Khodagholi

  4. Department of Physiology, Faculty of Medical Sciences, Tarbiat Modares University, Tehran, Iran

    Forough Foolad

  5. Department of Physiology, Faculty of Medicine, Tehran Medical Sciences, Islamic Azad University, Tehran, Iran

    Shahrzad Khakpour & Batool Ghorbani Yekta

  6. Herbal Pharmacology Research Center, Tehran Medical Sciences, Islamic Azad University, Tehran, Iran

    Batool Ghorbani Yekta

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  1. Nayereh Zare
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Contributions

NZ designed and performed the molecular experiments, analyzed the data, and wrote the manuscript. NM performed the conception, experimental design, supervision, and reviewed the manuscript. SHM performed the molecular experiments, analyzed the data, and wrote the manuscript. FF analyzed the data and reviewed the manuscript. SK contributed to design and reviewed the manuscript. ZM performed the molecular experiment and analyzed the data. FK performed the conception, experimental design, and reviewed the manuscript. BGY performed the conception, experimental design, supervision, analysis, interpretation, and reviewed the manuscript. All authors read and approved the final manuscript.

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Correspondence to Batool Ghorbani Yekta.

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Zare, N., Maghsoudi, N., Mirbehbahani, S.H. et al. Prenatal Methamphetamine Hydrochloride Exposure Leads to Signal Transduction Alteration and Cell Death in the Prefrontal Cortex and Amygdala of Male and Female Rats’ Offspring. J Mol Neurosci 72, 2233–2241 (2022). https://doi.org/10.1007/s12031-022-02062-2

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