Paternal cocaine taking elicits epigenetic remodeling and memory deficits in male progeny

M. E. Wimmer, L. A. Briand, B. Fant, L. A. Guercio, A. C. Arreola, H. D. Schmidt, S. Sidoli, Y. Han, B. A. Garcia, R. C. Pierce

Research output: Contribution to journalArticle

16 Citations (Scopus)

Abstract

Paternal environmental perturbations including exposure to drugs of abuse can produce profound effects on the physiology and behavior of offspring via epigenetic modifications. Here we show that adult drug-naive male offspring of cocaine-exposed sires have memory formation deficits and associated reductions in NMDA receptor-mediated hippocampal synaptic plasticity. Reduced levels of the endogenous NMDA receptor co-agonist d-serine were accompanied by increased expression of the d-serine degrading enzyme d-amino acid oxidase (Dao1) in the hippocampus of cocaine-sired male progeny. Increased Dao1 transcription was associated with enrichment of permissive epigenetic marks on histone proteins in the hippocampus of male cocaine-sired progeny, some of which were enhanced near the Dao1 locus. Finally, hippocampal administration of d-serine reversed both the memory formation and synaptic plasticity deficits. Collectively, these results demonstrate that paternal cocaine exposure produces epigenetic remodeling in the hippocampus leading to NMDA receptor-dependent memory formation and synaptic plasticity impairments only in male progeny, which has significant implications for the male descendants of chronic cocaine users.

Original languageEnglish (US)
Pages (from-to)1641-1650
Number of pages10
JournalMolecular Psychiatry
Volume22
Issue number11
DOIs
StatePublished - Nov 1 2017
Externally publishedYes

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Memory Disorders
Cocaine
Epigenomics
Neuronal Plasticity
N-Methyl-D-Aspartate Receptors
Serine
Hippocampus
Paternal Exposure
Histone Code
Street Drugs
Oxidoreductases
Amino Acids
Enzymes
Pharmaceutical Preparations
Proteins

ASJC Scopus subject areas

  • Molecular Biology
  • Psychiatry and Mental health
  • Cellular and Molecular Neuroscience

Cite this

Wimmer, M. E., Briand, L. A., Fant, B., Guercio, L. A., Arreola, A. C., Schmidt, H. D., ... Pierce, R. C. (2017). Paternal cocaine taking elicits epigenetic remodeling and memory deficits in male progeny. Molecular Psychiatry, 22(11), 1641-1650. https://doi.org/10.1038/mp.2017.8

Paternal cocaine taking elicits epigenetic remodeling and memory deficits in male progeny. / Wimmer, M. E.; Briand, L. A.; Fant, B.; Guercio, L. A.; Arreola, A. C.; Schmidt, H. D.; Sidoli, S.; Han, Y.; Garcia, B. A.; Pierce, R. C.

In: Molecular Psychiatry, Vol. 22, No. 11, 01.11.2017, p. 1641-1650.

Research output: Contribution to journalArticle

Wimmer, ME, Briand, LA, Fant, B, Guercio, LA, Arreola, AC, Schmidt, HD, Sidoli, S, Han, Y, Garcia, BA & Pierce, RC 2017, 'Paternal cocaine taking elicits epigenetic remodeling and memory deficits in male progeny', Molecular Psychiatry, vol. 22, no. 11, pp. 1641-1650. https://doi.org/10.1038/mp.2017.8
Wimmer ME, Briand LA, Fant B, Guercio LA, Arreola AC, Schmidt HD et al. Paternal cocaine taking elicits epigenetic remodeling and memory deficits in male progeny. Molecular Psychiatry. 2017 Nov 1;22(11):1641-1650. https://doi.org/10.1038/mp.2017.8
Wimmer, M. E. ; Briand, L. A. ; Fant, B. ; Guercio, L. A. ; Arreola, A. C. ; Schmidt, H. D. ; Sidoli, S. ; Han, Y. ; Garcia, B. A. ; Pierce, R. C. / Paternal cocaine taking elicits epigenetic remodeling and memory deficits in male progeny. In: Molecular Psychiatry. 2017 ; Vol. 22, No. 11. pp. 1641-1650.
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