Neurocognitive impairments in rat offspring after maternal exposure to Vortioxetine: Involvement of BDNF, apoptosis and cholinergic mediated signaling pathways.

Depression in pregnant women raises concerns about the safety of antidepressants use, particularly its impact on offspring's neurocognition. This study investigates the effects of maternal exposure to Vortioxetine (VOX) on the neurocognitive development of rat offspring. Pregnant Wistar rats were administered clinically pertinent doses of VOX, 1mg/kg/day or 2mg/kg/day from gestational day 6 to 21. The dams delivered their offspring naturally and reared until postnatal day (PND) 70. Offspring of both sexes were assessed for postnatal growth by measuring body weight from PND 1 to 70 weekly and cognitive function using Morris Water Maze (MWM) test and Passive Avoidance Learning test from PND 49 to 70. After behavioral assessments, adult rat offspring were sacrificed, and their brains were dissected out for assessment of brain morphology as well as biochemical analysis. The results demonstrated that VOX exposure potentially impaired cognitive performance, evidenced by increased latency in MWM and Passive Avoidance Learning tests. Additionally, it led to decreased body weight, altered brain morphology, and disrupted neurobiochemical profiles. Specifically, VOX 2mg/kg exposure significantly reduced brain-derived neurotrophic factor (BDNF) expression, increased pro-apoptotic BAX expression, decreased anti-apoptotic Bcl-2 expression, and elevated acetylcholinesterase (AChE) activity in the hippocampus. Lower dose of VOX (1mg/kg) did not show significant adverse effects on neurocognition, suggesting a dose-dependent impact. No sex specific neurocognitive deficits were observed in current study. These findings indicate that while VOX may offer a safer profile compared to SSRIs, high doses during pregnancy can still result in neurocognitive impairments in offspring.

• Publication year

  2024

• Venue

  Reproductive Toxicology

• Publication date

  2024-11-01

• Fields of study

  Medicine

• Identifiers
  DOI 10.1016/j.reprotox.2024.108746PMID 39557222
• External record

  Open on Semantic Scholar

• Source metadata

  Semantic Scholar, PubMed

• No claims are published for this paper.

• No concepts are published for this paper.

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