Up-regulation of PI3K‑Akt‑mTOR signaling pathway in neurons affects cognitive functions and social interactions in a mouse model

• Autorzy: Chwin N. , Kiryk A. , Bijoch L. , Hamed A. , Konopka W.
• Języki publikacji: EN

Abstrakty

EN

INTRODUCTION: The PI3K-Akt-mTOR pathway plays an important role in neuronal plasticity. In normal conditions, activity of this pathway is controlled by Pten phosphatase. AIM(S): We showed that loss of Pten gene in neurons evoked long-term up-regulation of PI3K-Akt-mTOR and temporarily improved learning and memory in mouse models. Moreover, we observed changes in mice vocalization during social interaction and in cellular physiology during electrophysiological recordings. METHOD(S): Mice model: Inactivation of Pten gene was investigated in 2 models: Pten/CaMKCreERT2, and Pten‑flox injected by AAV vectors. The mutation was restricted to forebrain and hippocampal neurons, respectively. Behavioral testing: Both models and respective controls were tested in a learning and memory test in IntelliCage. We measured spatial learning with appetitive behaviors. We also measured the ability to associate an aversive stimulus in the Contextual Fear Conditioning and social interaction in the Three Chamber Sociability and Social Novelty. Life span: Long‑term activity of the PI3K-Akt-mTOR pathway led to increased mortality of Pten/CaMKCreERT2 mutants. RESULTS: IntelliCage: We discovered better performance of Pten/CaMKCreERT2 mutants in the PL task. The memory improvement lasted to even 24 hours before the death. FC task: Mice developed stronger aversive memory than controls, manifested as increased freezing behavior. Both mutant models showed improved cognitive functions, and Pten/CaMKCreERT2 mice showed a decrease life span. CONCLUSIONS: Pten-flox-AAV mice developed enhanced contextual fear memory before neurodegeneration in hippocampus occurred and Pten-flox-AAV mice had intensified vocalizations with disturbed sound architecture in social interactions.

• Wydawca: -
• Czasopismo: Acta Neurobiologiae Experimentalis
• Rocznik: 2019
• Tom: 79
• Numer: Suppl.1
• Opis fizyczny: p.LXXII-LXXIII

Twórcy

autor

Chwin N.

• Laboratory of Animal Models, Nencki Institute of Experimental Biology, Polish Academy of Sciences, Warsaw, Poland

autor

Kiryk A.

• Laboratory of Animal Models, Nencki Institute of Experimental Biology, Polish Academy of Sciences, Warsaw, Poland

autor

Bijoch L.

• Laboratory of Neurobiology, Nencki Institute of Experimental Biology, Polish Academy of Sciences, Warsaw, Poland

autor

Hamed A.

• Laboratory of Spatial Memory, Nencki Institute of Experimental Biology, Polish Academy of Sciences, Warsaw, Poland

autor

Konopka W.

• Laboratory of Animal Models, Nencki Institute of Experimental Biology, Polish Academy of Sciences, Warsaw, Poland