Grand-paternal age and the development of autism-like symptoms in mice progeny.
Advanced paternal age (APA) contributes to the risk of autism spectrum disorders (ASDs) in children. In this study, we used a mouse model to investigate the effects of APA on behavioral features related to autistic syndromes (that is, social deficits, communication impairments and stereotypic/repetitive behaviors). We also examined whether such effects are transmitted across generations. To do this, males aged 15 months (APA) and 4 months (control) were bred with 4-month-old females, and the resulting offspring (F1) and their progeny (F2; conceived by 4-month-old parents) were tested for the presence and severity of ASD-like behaviors. Our results indicate that APA resulted in offspring that displayed distinctive symptoms of ASD. We found that both F1 conceived from old fathers and F2 derived from old grandfathers displayed increased ultrasound vocalization (USV) activity, decreased sociability, increased grooming activity and increased anxiety-like responses. Moreover, such abnormalities were partially transmitted to the second generation of mice, having APA grandfathers. In conclusion, our study suggests that the risk of ASD could develop over generations, consistent with heritable mutations and/or epigenetic alterations associated with APA.
1] Faculty of Veterinary Medicine, University of Teramo, Teramo, Italy [2] Institute of Genetics and Animal Breeding, Polish Academy of Sciences, Jastrzebiec, Poland.
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Sampino
Institute of Genetics and Animal Breeding, Polish Academy of Sciences, Jastrzebiec, Poland.
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Juszczak
Faculty of Veterinary Medicine, University of Teramo, Teramo, Italy.
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F
Zacchini
1] Faculty of Biology, University of Gdansk, Gdansk, Poland [2] Department of Pharmacology, Toxicology and Neuroscience, Louisiana State University Health Sciences Center (LSUHSC), Shreveport, LA, USA.
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Swiergiel
Institute of Genetics and Animal Breeding, Polish Academy of Sciences, Jastrzebiec, Poland.
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JA
Modlinski
Faculty of Veterinary Medicine, University of Teramo, Teramo, Italy.
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Loi
1] Faculty of Veterinary Medicine, University of Teramo, Teramo, Italy [2] Institute of Genetics and Animal Breeding, Polish Academy of Sciences, Jastrzebiec, Poland.
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Ptak
D000367:Age Factors; D000818:Animals; D001522:Behavior, Animal / Q000502:physiology*; D002659:Child Development Disorders, Pervasive / Q000209:etiology* / Q000235:genetics; D004195:Disease Models, Animal; D005260:Female; D008297:Male; D051379:Mice; D010331:Paternal Age; D011897:Random Allocation