Neuronal subset-specific deletion of Pten results in aberrant Wnt signaling and memory impairments.

The canonical Wnt and PI3K/Akt/mTOR pathways both play critical roles in brain development early in life. There is extensive evidence of how each pathway is involved in neuronal and synaptic maturation, however, how these molecular networks interact requires further investigation. The present study examines the effect of neuronal subset-specific deletion of phosphatase and tensin homolog (Pten) in mice on Wnt signaling protein levels and associated cognitive impairments.

Superimposing Status Epilepticus on Neuron Subset-Specific PTEN Haploinsufficient and Wild Type Mice Results in Long-term Changes in Behavior.

We evaluated the effects of superimposing seizures on a genetic mutation with known involvement in both Autism Spectrum Disorder and in epilepsy. Neuron-subset specific (NS)-Pten heterozygous (HT) and wildtype (WT) adult mice received either intraperitoneal injections of kainic acid (20 mg/kg) to induce status epilepticus or the vehicle (saline). Animals then received a battery of behavioral tasks in order to evaluate activity levels, anxiety, repetitive-stereotyped behavior, social behavior, learning and memory.

Deletion of PTEN produces autism-like behavioral deficits and alterations in synaptic proteins.

Many genes have been implicated in the underlying cause of autism but each gene accounts for only a small fraction of those diagnosed with autism. There is increasing evidence that activity-dependent changes in neuronal signaling could act as a convergent mechanism for many of the changes in synaptic proteins. One candidate signaling pathway that may have a critical role in autism is the PI3K/AKT/mTOR pathway.

Deletion of PTEN produces deficits in conditioned fear and increases fragile X mental retardation protein.

The phosphatase and tensin homolog detected on chromosome 10 (PTEN) gene product modulates activation of the phosphatidylinositol 3-kinase (PI3K)/AKT pathway. The PI3K pathway has been found to be involved in the regulation of the fragile X mental retardation protein, which is important for long-term depression and in the formation of new memories. We used delayed fear conditioning and trace fear conditioning to determine learning and memory deficits in neuron subset-specific Pten (NS-Pten) conditional knockout (KO) mice.