Monoamine oxidase A and A/B knockout mice display autistic-like features
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Issue Date
2013-05Author
Bortolato, Marco
Godar, Sean C.
Alzghoul, Loai
Zhang, Junlin
Darling, Ryan D.
Simpson, Kimberly L.
Bini, Valentina
Chen, Kevin
Wellman, Cara L.
Lin, Rick C. S.
Shih, Jean C.
Publisher
Cambridge University Press
Type
Article
Article Version
Scholarly/refereed, publisher version
Metadata
Show full item recordAbstract
Converging lines of evidence show that a sizable subset of autism-spectrum disorders (ASDs) is characterized by increased blood levels of serotonin (5-hydroxytryptamine, 5-HT), yet the mechanistic link between these two phenomena remains unclear. The enzymatic degradation of brain 5-HT is mainly mediated by monoamine oxidase (MAO)A and, in the absence of this enzyme, by its cognate isoenzyme MAOB. MAOA and A/B knockout (KO) mice display high 5-HT levels, particularly during early developmental stages. Here we show that both mutant lines exhibit numerous behavioural hallmarks of ASDs, such as social and communication impairments, perseverative and stereotypical responses, behavioural inflexibility, as well as subtle tactile and motor deficits. Furthermore, both MAOA and A/B KO mice displayed neuropathological alterations reminiscent of typical ASD features, including reduced thickness of the corpus callosum, increased dendritic arborization of pyramidal neurons in the prefrontal cortex and disrupted microarchitecture of the cerebellum. The severity of repetitive responses and neuropathological aberrances was generally greater in MAOA/B KO animals. These findings suggest that the neurochemical imbalances induced by MAOA deficiency (either by itself or in conjunction with lack of MAOB) may result in an array of abnormalities similar to those observed in ASDs. Thus, MAOA and A/B KO mice may afford valuable models to help elucidate the neurobiological bases of these disorders and related neurodevelopmental problems
Description
This is the published version, also available electronically from http://journals.cambridge.org/action/displayAbstract?fromPage=online&aid=8876069&fileId=S1461145712000715
ISSN
1461-1457Collections
- Pharmacy Scholarly Works [293]
Citation
Bortolato, Marco et al. (2013). Monoamine oxidase A and A/B knockout mice display autistic-like features. The International Journal of Neuropsychopharmacology 16(4):869-888. http://dx.doi.org/10.1017/S1461145712000715
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