Tuberous Sclerosis

Autism’s Unexpected Link to Cancer Gene

Source: 
The New York Times
Date Published: 
August 11, 2013
Abstract: 

Researchers have recently discovered that two seemingly unrelated conditions, autism and cancer, share an unexpected connection. Some people with autism have specific mutated cancer or tumor genes that scientists believe caused their autism. While this does not apply to all people with autism, just the ones with the mutated gene, it is a very illuminating discovery in the field.

Researchers Swing Toward Monkey Models of Autism

Source: 
SFARI
Date Published: 
October 18, 2012
Abstract: 

Scientists reveal efforts to create transgenic monkey models of autism. Compared to mice and rats, these animals are more genetically similar to humans, and display more complex social and communicative behaviors.

Autism May Involve Disordered White Matter in the Brain

Source: 
Science Daily
Abstract: 

While it is still unclear what's different in the brains of people with autism spectrum disorders, more and more evidence from genetic and cell studies points to abnormalities in how neurons connect to each other.

Another Genetic Clue To Autism: Opposite Malfunctions Have Same Result

Source: 
Medical News Today
Date Published: 
November 25, 2011
Abstract: 

In most cases, autism is caused by a combination of genetic factors, but some cases, such as Fragile X syndrome, can be traced to a variation in a single gene that causes overproduction of proteins in brain synapses. Now a new study led by the same MIT neuroscientist who made that discovery, finds that tuberous sclerosis is caused by a malfunction at the opposite end of the spectrum: underproduction of the synaptic proteins.

Tuberous Sclerosis Complex Proteins Control Axon Formation

Source: 
Genes Development, Choi, DiNardo, et al
Date Published: 
2008
Year Published: 
2008

Axon formation is fundamental for brain development and function. TSC1 and TSC2 are two genes, mutations in which cause tuberous sclerosis complex (TSC), a disease characterized by tumor predisposition and neurological abnormalities including epilepsy, mental retardation, and autism. Here we show that Tsc1 and Tsc2 have critical functions in mammalian axon formation and growth. Overexpression of Tsc1/Tsc2 suppresses axon formation, whereas a lack of Tsc1 or Tsc2 function induces ectopic axons in vitro and in the mouse brain. Tsc2 is phosphorylated and inhibited in the axon but not dendrites. Inactivation of Tsc1/Tsc2 promotes axonal growth, at least in part, via up-regulation of neuronal polarity SAD kinase, which is also elevated in cortical tubers of a TSC patient. Our results reveal key roles of TSC1/TSC2 in neuronal polarity, suggest a common pathway regulating polarization/growth in neurons and cell size in other tissues, and have implications for the understanding of the pathogenesis of TSC and associated neurological disorders and for axonal regeneration.

Reversal of Learning Deficits in a Ts2+/- Mouse Model of Tuberous Sclerosis

Source: 
Nature Medicine, Ehninger, Han, et al
Date Published: 
2008
Year Published: 
2008

Tuberous sclerosis is a single-gene disorder caused by heterozygous mutations in the TSC1 (9q34) or TSC2 (16p13.3) gene and is frequently associated with mental retardation, autism and epilepsy. Even individuals with tuberous sclerosis and a normal intelligence quotient (approximately 50%) are commonly affected with specific neuropsychological problems, including long-term and working memory deficits. Here we report that mice with a heterozygous, inactivating mutation in the Tsc2 gene (Tsc2(+/-) mice) show deficits in learning and memory. Cognitive deficits in Tsc2(+/-) mice emerged in the absence of neuropathology and seizures, demonstrating that other disease mechanisms are involved. We show that hyperactive hippocampal mammalian target of rapamycin (mTOR) signaling led to abnormal long-term potentiation in the CA1 region of the hippocampus and consequently to deficits in hippocampal-dependent learning. These deficits included impairments in two spatial learning tasks and in contextual discrimination. Notably, we show that a brief treatment with the mTOR inhibitor rapamycin in adult mice rescues not only the synaptic plasticity, but also the behavioral deficits in this animal model of tuberous sclerosis. The results presented here reveal a biological basis for some of the cognitive deficits associated with tuberous sclerosis, and they show that treatment with mTOR antagonists ameliorates cognitive dysfunction in a mouse model of this disorder.