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Paternal exposure to methylphenidate causes behavioral abnormalities in grandchildren.

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Paternal exposure to methylphenidate (MPH) in ADHD treatment may cause anxiety-like behaviors in offspring across generations. This suggests MPH-induced epigenetic changes in germ cells influence subsequent generations.

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Area of Science:

  • Neurodevelopmental disorders
  • Epigenetics
  • Generational health

Background:

  • Attention-deficit/hyperactivity disorder (ADHD) is a common neurodevelopmental disorder treated with methylphenidate (MPH).
  • Paternal environmental factors can impact offspring health, potentially leading to transgenerational effects.
  • Previous studies showed MPH administration to sires affected F1 generation behavior and memory.

Purpose of the Study:

  • To investigate the transgenerational effects of paternal methylphenidate (MPH) exposure on the F2 generation.
  • To examine the impact on development, behavior, and brain gene expression.
  • To explore the extent of MPH-induced epigenetic modifications across generations.

Main Methods:

  • Paternal administration of MPH to mice.
  • Assessment of F2 generation development, including birth rates, survival, body weight, and motor development.
  • Behavioral analyses (anxiety, learning, memory) in F2 offspring.
  • Transcriptome analysis of the female F2 cortex.

Main Results:

  • MPH exposure did not affect birth rates or survival but reduced F2 body weight.
  • Transient delays in motor development were observed, normalizing by weaning.
  • Reduced anxiety-like behaviors were noted in the MPH group, especially in females; learning and memory remained unaffected.
  • Transcriptome analysis indicated activation of neuroplasticity pathways in female F2 offspring.

Conclusions:

  • Paternal MPH exposure can induce behavioral abnormalities in the F2 generation, suggesting transgenerational epigenetic inheritance.
  • Observed effects, particularly reduced anxiety, may be mediated by epigenetic changes in germ cells.
  • This study highlights the potential for environmental factors, including medication, to influence offspring health beyond direct exposure.