1. Baronio D, Castro K, Gonchoroski T, de Melo GM, Nunes GD, Bambini-Junior V, Gottfried C, Riesgo R. {{Effects of an H3R Antagonist on the Animal Model of Autism Induced by Prenatal Exposure to Valproic Acid}}. {PloS one}. 2015;10(1):e0116363.
Autism spectrum disorders (ASD) are a group of neurodevelopmental disorders primarily characterized by impaired social interaction and communication, and by restricted repetitive behaviors and interests. Ligands of histamine receptor 3 (H3R) are considered potential therapeutic agents for the treatment of different brain disorders and cognitive impairments. Considering this, the aim of the present study is to evaluate the actions of ciproxifan (CPX), an H3R antagonist, on the animal model of autism induced by prenatal exposure to valproic acid (VPA). Swiss mice were prenatally exposed to VPA on embryonic day 11 and assessed for social behavior, nociceptive threshold and repetitive behavior at 50 days of life. The treatment with CPX (3 mg/kg) or saline was administered 30 minutes before each behavioral test. The VPA group presented lower sociability index compared to VPA animals that were treated with CPX. Compared to the Control group, VPA animals presented a significantly higher nociceptive threshold, and treatment with CPX was not able to modify this parameter. In the marble burying test, the number of marbles buried by VPA animals was consistent with markedly repetitive behavior. VPA animals that received CPX buried a reduced amount of marbles. In summary, we report that an acute dose of CPX is able to attenuate sociability deficits and stereotypies present in the VPA model of autism. Our findings have the potential to help the investigations of both the molecular underpinnings of ASD and of possible treatments to ameliorate the ASD symptomatology, although more research is still necessary to corroborate and expand this initial data.
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2. Visser EM, Berger HJ, Van Schrojenstein Lantman-De Valk HM, Prins JB, Teunisse JP. {{Cognitive shifting and externalising problem behaviour in intellectual disability and autism spectrum disorder}}. {Journal of intellectual disability research : JIDR}. 2015 Jan 5.
BACKGROUND: Behavioural problems are frequently reported in residential care for people with an intellectual disability (ID) in particular when they are additionally diagnosed with autism spectrum disorder (ASD). There are indications that impairment in cognitive shifting may be associated with problem behaviour. The objectives of this study were (1) to examine the relationship of cognitive shifting and severity of ASD symptoms with externalising problem behaviour in individuals with ID, with and without ASD, and (2) to examine whether a diagnosis based on shifting impairment is more predictive of externalising problem behaviour than an ASD diagnosis. METHOD: Participants consisted of adolescents and young adults with mild ID, with and without ASD (n = 41). Pearson intercorrelations were computed to explore the relationship between shifting impairment and severity of ASD symptoms on the one hand and ratings of externalising problem behaviour on the other hand. t-Tests were performed to analyse differences in externalising problem behaviour. RESULTS: Unlike ASD symptom severity, shifting scores were found to be associated with externalising problem behaviour, but only if shifting was measured using rating scales and not when using neuropsychological tasks. Externalising problem behaviour scores significantly differed when groups were classified according to shifting impairment (impaired vs. non-impaired) but not when they were classified according to ID and ASD diagnoses. CONCLUSIONS: It is proposed to use a cognition-based approach when analysing problem behaviour, thus concentrating not so much on ID and ASD diagnosis and their corresponding symptoms, but rather placing the focus on cognitive symptoms.
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3. Yang H, Huh SO, Hong JS. {{Enhancement of Short-Term Memory by Methyl-6-(Phenylethynyl)-Pyridine in the BTBR T+tf/J Mouse Model of Autism Spectrum Disorder}}. {Endocrinology and metabolism (Seoul, Korea)}. 2015 Jan 5.
BACKGROUND: Autism spectrum disorder (ASD) encompasses a range of disorders that are characterized by social and communication deficits and repetitive behaviors. This study evaluated the effect of methyl-6-(phenylethynyl)-pyridine (MPEP), an antagonist of the mGluR5 metabotropic glutamate receptor, on memory enhancement in the BTBR T+tf/J (BTBR) mouse strain, which has been recognized as a model of ASD. METHODS: The pharmacological effects of MPEP on memory and motor coordination were assessed using the Morris water maze and rotarod tests in BTBR and C57BL/6J (B6) mice. Furthermore, we performed morphological analyses of cerebellar foliation in BTBR and B6 mice using hematoxylin and eosin staining. RESULTS: MPEP-treated BTBR mice exhibited improved learning and memory in the Morris water maze test. MPEP administration also improved motor coordination in the rotarod test. However, no significant difference was observed regarding the numbers of Purkinje cells in the cerebella of BTBR versus normal B6 mice. CONCLUSION: This study suggests that the mGluR5 antagonist MPEP has the potential to ameliorate learning and memory dysfunction and impaired motor coordination in BTBR mice. These results further suggest that the BTBR mouse model may be useful in pharmacological studies investigating drugs that could potentially alleviate cognitive dysfunction in ASD.
