Up-regulation of mTOR signaling pathway in forebrain neurons leads to improvement of cognitive functions in pten knock-out mice

• Autorzy: Chwin N. , Kiryk A. , Zglinicki B. , Konopka W.
• Języki publikacji: EN

Abstrakty

EN

INTRODUCTION: PI3K-Akt-mTOR pathway plays important role in long-term synaptic plasticity and memory formation. In our studies describing the Dicer1 gene knock-out model we have shown that improved learning and memory phenotype in these mice was related to up-regulation of the PI3K-Akt-mTOR pathway. In order to prove that the PI3K-Akt-mTOR pathway is crucial for observed phenotype we have generated Pten gene knock-out model in which this up-regulation is achieved by elevation of intracellular levels of phosphatidylinositide 3 in neurons. To examine cognitive functions in Pten model, we have used the IntelliCage system. AIM(S): The puropse of our research was to define the cognitive functions in Pten/CaMKCreERT2 mouse model. METHOD(S): Mouse model: We used Pten/CaMKCreERT2 mouse model in which up-regulation of mTOR activity was generated by mutation of Pten gene restricted to forebrain neurons induced by tamoxifen. Behavioral tests: Following induction of the mutation, Pten mutant mice and controls were tested in learning and memory test in the IntelliCage: a fully automated system for the behavioral assessment of mice that live in social groups. We measured spatial learning with appetitive reinforcement in place preference learning task. RESULTS: Life span: Long-term of PI3K-Akt-mTOR pathway activity in the brain led to increased mutant mice mortality. Pten mutants were able to survive no longer than 13 weeks after the induction of mutation. Place learning in IntelliCage: In the IntelliCage, housing and testing occur in the same cage that is a familiar environment, thus creating a unique opportunity to test behavior for a long-term period in relatively low-stress conditions without handling or social isolation. Using the system, we were able to discover the better performance of Pten mutants in place learning task. Moreover, improved memory was detectable even 24 hours before the death. CONCLUSIONS: Pten/CaMKCreERT2 mice show enhanced memory of rewarded place compare to control littermates. In mutants show decreased life span.

• Wydawca: -
• Czasopismo: Acta Neurobiologiae Experimentalis
• Rocznik: 2017
• Tom: 77
• Numer: Suppl.1
• Opis fizyczny: p.129-130

Twórcy

autor

Chwin N.

• Nencki Institute of Experimental Biology Polish Academy of Science, Neurobiology Centre, Warsaw, Poland

autor

Kiryk A.

• Nencki Institute of Experimental Biology Polish Academy of Science, Neurobiology Centre, Warsaw, Poland

autor

Zglinicki B.

• Nencki Institute of Experimental Biology Polish Academy of Science, Neurobiology Centre, Warsaw, Poland

autor

Konopka W.

• Nencki Institute of Experimental Biology Polish Academy of Science, Neurobiology Centre, Warsaw, Poland