Perinatal exposure of rats to the HIV drug efavirenz affects medial prefrontal cortex cytoarchitecture
Open accessAbstract
Efavirenz (EFV) is used for antiretroviral treatment of HIV infection, and successfully inhibits viral replication and mother-to-child transmission of HIV during pregnancy and childbirth. Unfortunately, the drug induces neuropsychiatric symptoms such as anxiety and depressed mood and potentially affects cognitive performance. EFV acts on, among others, the serotonin transporter and serotonin receptors that are expressed in the developing brain. Yet, how perinatal EFV exposure affects brain cytoarchitecture remains unclear. Here, we exposed pregnant and lactating rats to EFV, and examined in the medial prefrontal cortex (mPFC) of their adult offspring the effects of the maternal EFV exposure on cortical architecture. We observed a significant decrease in the number of cells, mainly mature neurons, in the infra/prelimbic and cingulate cortices of adult offspring. Next, we found an altered cortical cytoarchitecture characterized by a significant reduction in deep- and superficial-layer cells. This was accompanied by a sharp increase in programmed cell death, as we identified a significantly higher number of cleaved Caspase-3-positive cells. Finally, the serotonergic and dopaminergic innervation of the mPFC subdomains was increased. Thus, the perinatal exposure to EFV provoked in the mPFC of adult offspring cell death, significant changes in cytoarchitecture, and disturbances in serotonergic and dopaminergic innervation. Our results are important in the light of EFV treatment of HIV-positive pregnant women, and its effect on brain development and cognitive behavior.
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Perinatal exposure to antiretroviral drugs such as Efavirenz (EFV) to treat HIV leads to an altered prefrontal cytoarchitecture.
“Perinatal HIV infections can alter the course of brain development (see below), on the other hand perinatal exposure to antiretroviral drugs such as Efavirenz (EFV) to treat HIV leads to an altered prefrontal cytoarchitecture [335, 336].”
From Development of prefrontal cortex (2022) · cites this paper as [336]
The Abstract reports altered medial prefrontal cortex cytoarchitecture in adult offspring of rats exposed perinatally to efavirenz. The study does not establish that other antiretroviral drugs have this effect or that it occurs in humans receiving HIV treatment. (LLM, conf=0.88)
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References 73 · Cited by 6
- Authors
- Garcia, L. P., Van de Wijer, L., Hanswijk, S. I., Rando, J., Witteveen, J. S., Middelman, A., ter Heine, R., de Mast, Q., Martens, G. J. M., van der Ven, A. J. A. M., Schellekens, A. F. A., Homberg, J. R., & Kolk, S. M.
- Affiliations
- Radboud University Nijmegen (NL)
- Radboud University Medical Center (NL)
- Corresponding author
- Homberg, J.R.
- Kolk, S.M.
- Venue
- Biochemical Pharmacology
- Publisher
- Elsevier BV
- Published
- 2020-08
- Volume
- 178
- Pages
- 114050
- ISSN
- 0006-2952 (ISSN-L)
- OpenAlex
- W3027690745
- Cited by
- 6
- References
- 73
- Citations by year
- 2023: 4 · 2022: 1 · 2021: 1
- FWCI
- 1.44
- Type
- journal article
- Language
- en
- Open access
- hybrid
- doi.org
- Licence
- Locations
- Biochemical Pharmacology (publishedVersion, cc-by)
- PubMed (publishedVersion)
- Radboud Repository (Radboud University) (submittedVersion)
- Radboud Repository (Radboud University) (submittedVersion, other-oa)
- Funders
- Radboud Universitair Medisch Centrum
- Radboud Universiteit
- Coordenação de Aperfeiçoamento de Pessoal de Nível Superior
- Topics
- Health Sciences › Medicine › Pediatrics, Perinatology and Child Health › Prenatal Substance Exposure Effects
- Health Sciences › Medicine › Infectious Diseases › HIV/AIDS drug development and treatment
- Health Sciences › Medicine › Pediatrics, Perinatology and Child Health › Pharmacological Effects and Toxicity Studies
- Keywords
- efavirenz, perinatal drug exposure, prenatal drug exposure, medial prefrontal cortex, cortical cytoarchitecture, programmed cell death, caspase-3, serotonergic innervation, dopaminergic innervation, HIV antiretroviral drugs, brain development, anxiety, depression, cognitive impairment
- MeSH terms
- Alkynes, Animals, Animals, Newborn, Cyclopropanes, Female, Male, Pregnancy, Prenatal Exposure Delayed Effects, Rats, Wistar, Prefrontal Cortex, Reverse Transcriptase Inhibitors, Anti-HIV Agents, Benzoxazines, Rats
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