Vasoactive intestinal peptide antagonist treatment during mouse embryogenesis impairs social behavior and cognitive function of adult male offspring

• Published in: Experimental neurology Vol. 206; no. 1; pp. 101 - 113
• Main Authors: Hill, Joanna M., Cuasay, Katrina, Abebe, Daniel T.
• Format: Journal Article
• Language: English
• Published: Amsterdam Elsevier Inc 01.07.2007; Elsevier
• Subjects: Aging - physiology; Animals; Animals, Newborn; Autism; Autistic Disorder - etiology; Autistic Disorder - metabolism; Autistic Disorder - physiopathology; Avoidance Learning - drug effects; Avoidance Learning - physiology; Biological and medical sciences; Brain - drug effects; Brain - embryology; Brain - physiopathology; Cognition - drug effects; Cognition - physiology; Cognition Disorders - chemically induced; Cognition Disorders - metabolism; Cognition Disorders - physiopathology; Cued and contextual fear conditioning; Degenerative and inherited degenerative diseases of the nervous system. Leukodystrophies. Prion diseases; Disease Models, Animal; Female; Habituation, Psychophysiologic - drug effects; Habituation, Psychophysiologic - physiology; Immunomodulators; Male; Medical sciences; Mental Disorders - chemically induced; Mental Disorders - metabolism; Mental Disorders - physiopathology; Mice; Neurodevelopmental disorder; Neurology; Neuropeptide; Peptides - pharmacology; Pharmacology. Drug treatments; Pregnancy; Prenatal Exposure Delayed Effects - chemically induced; Prenatal Exposure Delayed Effects - metabolism; Prenatal Exposure Delayed Effects - physiopathology; Sex Characteristics; Sex differences; Smell - drug effects; Smell - physiology; Sociability; Social approach; Social Behavior; Vasoactive Intestinal Peptide - antagonists & inhibitors; Vasoactive Intestinal Peptide - metabolism; Autism; Cued and contextual fear conditioning; Social approach; Sex differences; Sociability; Neurodevelopmental disorder; Neuropeptide; Cell culture; Animal model; Embryo; Cognitive disorder; Growth; Central nervous system; Sex; Developmental disorder; Mental retardation; Encephalon; Behavioral disorder; Social behavior; Neural tube; Conditioning; Social aspect; Deficiency; Rodentia; Interference; Pregnancy; Fear; Vertebrata; Mammalia; Treatment; Mouse; Social interaction; Animal; Vasoactive intestinal peptide; Intellectual deficiency; Surgical approach
• ISSN: 0014-4886; 1090-2430
• DOI: 10.1016/j.expneurol.2007.04.004

Vasoactive intestinal peptide (VIP) is a regulator of rodent embryogenesis during the period of neural tube closure. VIP enhanced growth in whole cultured mouse embryos; treatment with a VIP antagonist during embryogenesis inhibited growth and development. VIP antagonist treatment during embryogenesis also had permanent effects on adult brain chemistry and impaired social recognition behavior in adult male mice. The neurological deficits of autism appear to be initiated during neural tube closure and social behavior deficits are among the key characteristics of this disorder that is more common in males and is frequently accompanied by mental retardation. The current study examined the blockage of VIP during embryogenesis as a model for the behavioral deficits of autism. Treatment of pregnant mice with a VIP antagonist during embryonic days 8 through 10 had no apparent effect on the general health or sensory or motor capabilities of adult offspring. However, male offspring exhibited reduced sociability in the social approach task and deficits in cognitive function, as assessed through cued and contextual fear conditioning. Female offspring did not show these deficiencies. These results suggest that this paradigm has usefulness as a mouse model for aspects of autism as it selectively impairs male offspring who exhibit the reduced social behavior and cognitive dysfunction seen in autism. Furthermore, the study indicates that the foundations of some aspects of social behavior are laid down early in mouse embryogenesis, are regulated in a sex specific manner and that interference with embryonic regulators such as VIP can have permanent effects on adult social behavior.