Association between SNAP-25 gene polymorphisms and cognition in autism: Functional consequences and potential therapeutic strategies

D. Braida, F. R. Guerini, L. Ponzoni, I. Corradini, S. De Astis, L. Pattini, E. Bolognesi, R. Benfante, D. Fornasari, M. Chiappedi, A. Ghezzo, M. Clerici, M. Matteoli, M. Sala

Research output: Contribution to journalArticle

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Abstract

Synaptosomal-associated protein of 25 kDa (SNAP-25) is involved in different neuropsychiatric disorders, including schizophrenia and attention-deficit/hyperactivity disorder. Consistently, SNAP-25 polymorphisms in humans are associated with hyperactivity and/or with low cognitive scores. We analysed five SNAP-25 gene polymorphisms (rs363050, rs363039, rs363043, rs3746544 and rs1051312) in 46 autistic children trying to correlate them with Childhood Autism Rating Scale and electroencephalogram (EEG) abnormalities. The functional effects of rs363050 single-nucleotide polymorphism (SNP) on the gene transcriptional activity, by means of the luciferase reporter gene, were evaluated. To investigate the functional consequences that SNAP-25 reduction may have in children, the behaviour and EEG of SNAP-25+/- adolescent mice (SNAP-25+/+) were studied. Significant association of SNAP-25 polymorphism with decreasing cognitive scores was observed. Analysis of transcriptional activity revealed that SNP rs363050 encompasses a regulatory element, leading to protein expression decrease. Reduction of SNAP-25 levels in adolescent mice was associated with hyperactivity, cognitive and social impairment and an abnormal EEG, characterized by the occurrence of frequent spikes. Both EEG abnormalities and behavioural deficits were rescued by repeated exposure for 21 days to sodium salt valproate (VLP). A partial recovery of SNAP-25 expression content in SNAP-25+/-hippocampi was also observed by means of western blotting. A reduced expression of SNAP-25 is responsible for the cognitive deficits in children affected by autism spectrum disorders, as presumably occurring in the presence of rs363050(G) allele, and for behavioural and EEG alterations in adolescent mice. VLP treatment could result in novel therapeutic strategies.

Original languageEnglish
Article numbere500
JournalTranslational Psychiatry
Volume5
Issue number1
DOIs
Publication statusPublished - Jan 1 2015

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Synaptosomal-Associated Protein 25
Autistic Disorder
Cognition
Genes
Electroencephalography
Therapeutics
Valproic Acid
Single Nucleotide Polymorphism
Child Behavior
Attention Deficit Disorder with Hyperactivity
Luciferases
Reporter Genes
Hippocampus
Schizophrenia

ASJC Scopus subject areas

  • Psychiatry and Mental health
  • Biological Psychiatry
  • Cellular and Molecular Neuroscience

Cite this

Association between SNAP-25 gene polymorphisms and cognition in autism : Functional consequences and potential therapeutic strategies. / Braida, D.; Guerini, F. R.; Ponzoni, L.; Corradini, I.; De Astis, S.; Pattini, L.; Bolognesi, E.; Benfante, R.; Fornasari, D.; Chiappedi, M.; Ghezzo, A.; Clerici, M.; Matteoli, M.; Sala, M.

In: Translational Psychiatry, Vol. 5, No. 1, e500, 01.01.2015.

Research output: Contribution to journalArticle

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