Publication Date:
2012-09-18
Description:
The genetic heterogeneity of autism poses a major challenge for identifying mechanism-based treatments. A number of rare mutations are associated with autism, and it is unclear whether these result in common neuronal alterations. Monogenic syndromes, such as fragile X, include autism as one of their multifaceted symptoms and have revealed specific defects in synaptic plasticity. We discovered an unexpected convergence of synaptic pathophysiology in a nonsyndromic form of autism with those in fragile X syndrome. Neuroligin-3 knockout mice (a model for nonsyndromic autism) exhibited disrupted heterosynaptic competition and perturbed metabotropic glutamate receptor-dependent synaptic plasticity, a hallmark of fragile X. These phenotypes could be rescued by reexpression of neuroligin-3 in juvenile mice, highlighting the possibility of reverting neuronal circuit alterations in autism after the completion of development.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Baudouin, Stephane J -- Gaudias, Julien -- Gerharz, Stefan -- Hatstatt, Laetitia -- Zhou, Kuikui -- Punnakkal, Pradeep -- Tanaka, Kenji F -- Spooren, Will -- Hen, Rene -- De Zeeuw, Chris I -- Vogt, Kaspar -- Scheiffele, Peter -- New York, N.Y. -- Science. 2012 Oct 5;338(6103):128-32. doi: 10.1126/science.1224159. Epub 2012 Sep 13.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Biozentrum of the University of Basel, Basel, Switzerland.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/22983708" target="_blank"〉PubMed〈/a〉
Keywords:
Animals
;
Autistic Disorder/*physiopathology
;
Cell Adhesion Molecules, Neuronal/genetics/metabolism
;
Disease Models, Animal
;
Fragile X Syndrome/genetics/*physiopathology
;
Male
;
Membrane Proteins/genetics/metabolism
;
Mice
;
Mice, Inbred C57BL
;
Mice, Knockout
;
Nerve Net/metabolism/physiopathology/ultrastructure
;
Nerve Tissue Proteins/genetics/metabolism
;
*Neuronal Plasticity
;
Synapses/metabolism/*physiology/ultrastructure
Print ISSN:
0036-8075
Electronic ISSN:
1095-9203
Topics:
Biology
,
Chemistry and Pharmacology
,
Computer Science
,
Medicine
,
Natural Sciences in General
,
Physics
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