Mouse Model Replicates Some Aspects of Learning Disorders

Defects in learning and memory may be reversed with drug, mouse study suggests

WEDNESDAY, June 25 (HealthDay News) -- A mouse model of tuberous sclerosis, a disorder associated with mental retardation, autism and epilepsy, replicates some aspects of the disorder such as the defects in learning and memory, which can be reversed with a drug, according to study findings published online June 22 in Nature Medicine.

Dan Ehninger, from the University of California Los Angeles, and colleagues generated mice with only one functional copy of the Tsc2 gene, one of two genes responsible for tuberous sclerosis.

The researchers found that the mice had deficits in hippocampal-dependent learning and memory, but did not have neuropathology or seizures. Hyperactive signaling through mTOR, a component of the Tsc2 signaling pathway, in the hippocampus led to abnormal long-term potentiation. This led to defects in hippocampal-dependent learning, including spatial learning and contextual discrimination. Treating mice with rapamycin, which inhibits mTOR, reversed both the behavioral deficits and synaptic plasticity, the authors report.

"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 ameliorated cognitive dysfunction in a mouse model of this disorder," Ehninger and colleagues conclude.

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