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Brainstem expression of SLC6A4, HTR2C, NGF, BDNF, TRKANGF, TRKBBDNF and P75NTR following paternal alcohol exposure in the male mouse

Giampiero Ferraguti, Claudia Codazzo, Carla Petrella, Roberto Coccurello, Mauro Ceccanti, Marco Fiore


We previously showed in the mouse that paternal preconception alcohol exposure (PPAE) affects alcohol sensitivity by analyzing postnatal alcohol preference in the offspring. In this mouse study by using the same animals of the previous investigation we aimed at examining whether or not PPAE may disrupt the epigenetic regulation of postnatal alcohol sensitivity in the offspring by investigating pathways regulating mood, emotion, serotonergic tone and neurotrophins such as nerve growth factor (NGF) and brain-derived neurotrophic factor (BDNF). We analyzed the brainstem gene expression of  serotonin transporter Solute Carrier Family 6 Member4 (SLC6A4), 5-Hydroxytryptamine Receptor 2C (HTR2C) binding the neurotransmitter serotonin, and NGF, BDNF and their tropomyosin receptor kinase A (TrkANGF) and B (TrKBBDNF) (high-affinity NGF and BDNF receptors) and p75NTR (low-affinity, pan-neurotrophins receptor) in adult offspring that underwent or not postnatal alcohol exposure. We found SLC6A4 elevation and decreased HTR2C in the offspring of chronic alcohol-exposed sires. We also disclosed p75NTR elevation in the offspring of chronically exposed sires as well as postnatal sensitization to low alcohol doses in the offspring of chronically exposed sires for both TrKBBDNF and BDNF. In our PPAE mouse model, where genotype effects can be carefully measured, we observed that the sires’ exposure to alcohol before mating might disrupt the sensitivity to the serotonergic/neurotrophic-associated effects of alcohol influencing the postnatal alcohol preference in the offspring.


SLC6A4; BDNF; NGF; TrkANGF; TrKBBDNF; HTR2C; p75NTR; Brainstem; Epigenetic; Pre-conceptual Paternal Alcohol Drinking

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About The Authors

Giampiero Ferraguti
Department of Experimental Medicine, Sapienza University Hospital of Rome

Claudia Codazzo
Department of Experimental Medicine, Sapienza University Hospital of Rome

Carla Petrella
Institute of Biochemistry and Cell Biology, IBBC-CNR, Rome

Roberto Coccurello
Institute for Complex System, ISC-CNR, Rome

IRCCS - S. Lucia Foundation (FSL), Rome

Mauro Ceccanti
Centro Riferimento Alcologico Regione Lazio, ASL Roma 1, Rome

Marco Fiore
Institute of Biochemistry and Cell Biology, IBBC-CNR, Rome

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