Dendritic spine dysgenesis in autism related disorders. (5th August 2015)

• Record Type: Journal Article
• Authors: Phillips, Mary; Pozzo-Miller, Lucas
• Is Part Of: Neuroscience letters. Volume 601(2015)
• Page Start: 30
• Page End: 40
• Publication Date: 2015-08-05
• Subjects: Glu glutamate -- Ras rat sarcoma proto-oncogenic G-protein -- MEK MAPK kinase -- ERK extracellular signal-related kinase -- Rheb RAS homolog enriched in brain -- Mnk MAP kinases phosphorylate -- elF4E eukaryotic initiation factor 4E -- 4E-BP eukaryotic translation initiation factor 4E binding protein -- S6 ribosomal protein S6 -- S6K S6 kinase -- 40S eukaryotic small ribosomal subunit -- PI3K phosphoinositide 3-kinase -- PDK phosphoinositide-dependent kinase -- P phosphate; mTOR -- mGluR -- TrkB -- Fragile X -- Rett syndrome -- MeCP2 -- Intellectual disability; Neurology -- Periodicals; Neurology -- Periodicals; Research -- Periodicals; Neurologie -- Périodiques; Neuroanatomie -- Périodiques; Neuropharmacologie -- Périodiques; Neurophysiologie -- Périodiques; Neurology; Periodicals; Electronic journals; 617.48
• DOI: 10.1016/j.neulet.2015.01.011
• Languages: English
• ISSNs: 0304-3940

Abstract

Abstract: The activity-dependent structural and functional plasticity of dendritic spines has led to the long-standing belief that these neuronal compartments are the subcellular sites of learning and memory. Of relevance to human health, central neurons in several neuropsychiatric illnesses, including autism related disorders, have atypical numbers and morphologies of dendritic spines. These so-called dendritic spine dysgeneses found in individuals with autism related disorders are consistently replicated in experimental mouse models. Dendritic spine dysgenesis reflects the underlying synaptopathology that drives clinically relevant behavioral deficits in experimental mouse models, providing a platform for testing new therapeutic approaches. By examining molecular signaling pathways, synaptic deficits, and spine dysgenesis in experimental mouse models of autism related disorders we find strong evidence for mTOR to be a critical point of convergence and promising therapeutic target.