Learn More
Overactivation of the mammalian target of rapamycin (mTOR) has been implicated in the pathogenesis of syndromic forms of autism spectrum disorders (ASDs), such as tuberous sclerosis complex, neurofibromatosis 1, and fragile X syndrome. Administration of mTORC1 (mTOR complex 1) inhibitors (e.g. rapamycin) in syndromic mouse models of ASDs improved behavior,(More)
The genetically inbred BTBR T+ Itpr3tf/J (BTBR) mouse is a proposed model of autism spectrum disorders (ASDs). Similar to several syndromic forms of ASDs, mTOR activity may be enhanced in this mouse strain as a result of increased Ras signaling. Recently, D-cycloserine, a partial glycineB site agonist that targets the NMDA receptor, was shown to improve the(More)
Currently, there are no medications that target core deficits of social communication and restrictive, repetitive patterns of behavior in persons with autism spectrum disorders (ASDs). Adults with Down syndrome (DS) display a progressive worsening of adaptive functioning, which is associated with Alzheimer's disease (AD)-like histopathological changes in(More)
Array comparative genomic hybridization (array CGH) has led to the identification of microdeletions of the proximal region of chromosome 15q between breakpoints (BP) 3 or BP4 and BP5 encompassing CHRNA7, the gene encoding the α7-nicotinic acetylcholine receptor (α7nAChR) subunit. Phenotypic manifestations of persons with these microdeletions are variable(More)
Balb/c mice are a model of impaired sociability and social motivation relevant to autism spectrum disorders (ASDs). Impaired sociability of 8-week old Balb/c mice is attenuated by agonists of the glycine(B) site on the NMDA receptor, such as d-cycloserine. Although ASDs are often recognized in toddlerhood, there is interest in earlier identification (e.g.,(More)
The NMDA receptor is a highly regulated glutamate-gated cationic channel receptor that has an important role in the regulation of sociability and cognition. The genetically-inbred Balb/c mouse has altered endogenous tone of NMDA receptor-mediated neurotransmission and is a model of impaired sociability, relevant to Autism Spectrum Disorders (ASDs). Because(More)
The genetically inbred Balb/cJ (Balb/c) mouse with functional alteration of its endogenous tone of NMDA receptor-mediated neurotransmission displays impaired sociability in a standard paradigm; this mouse strain has been proposed as a model of autism spectrum disorders (ASDs). Prior work showed that treatment of the Balb/c mouse with a centrally effective(More)
As persons with Down's syndrome (DS) age into the third decade and beyond, they develop Alzheimer's disease (AD)-like histopathological changes in brain and may manifest progressive worsening of adaptive functions. Increasingly, persons with DS have near-normal to normal life spans; thus, it has become a therapeutic imperative to preserve adaptive functions(More)
Tuberous Sclerosis Complex is one example of a syndromic form of autism spectrum disorder associated with disinhibited activity of mTORC1 in neurons (e.g., cerebellar Purkinje cells). mTORC1 is a complex protein possessing serine/threonine kinase activity and a key downstream molecule in a signaling cascade beginning at the cell surface with the(More)
The mammalian target of rapamycin (mTOR), a serine/threonine kinase, is a therapeutic target for many types of cancers. NMDA receptors regulate mTOR signalling activity; their inappropriate expression on several human cancer cell lines represents a potential therapeutic avenue to control dysregulated growth, division and invasiveness. Targeting these(More)