Mar 25, 2020

Inhibition of mTOR signaling by genetic removal of p70 S6 Kinase 1 leads to anxiety-like disorders

BioRxiv : the Preprint Server for Biology
Muriel KoehlN. Abrous

Abstract

The mechanistic target or rapamycin (mTOR) is a ubiquitously expressed kinase that acts through two complexes, mTORC1 and mTORC2, to regulate protein homeostasis as well as long lasting forms of synaptic and behavioral plasticity. Alteration of the mTOR pathway is classically involved in neurodegenerative disorders, and it has been linked to dysregulation of cognitive functions and affective states. However, information concerning the specific involvement of the p70 S6 kinase 1 (S6K1), a downstream target of the mTORC1 pathway, in learning and memory processes and in the regulation of affective states remains scant. To fill this gap, we exposed adult male mice lacking S6K1 to a battery of behavioral tests aimed at measuring their learning and memory capabilities by evaluating reference memory and flexibility with the Morris water maze, and associative memory using the contextual fear conditioning task. We also studied their anxiety- and depression-like behaviors by respectively performing elevated plus maze, open field, light-dark emergence tests, and sucrose preference and forced swim tests. We found that deleting S6K1 leads to a robust anxious phenotype concomitant with associative learning deficits; these symptoms are associ...Continue Reading

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Mentioned in this Paper

Small Nuclear RNA
Size
Repetitive Region
PIWIL1 gene
Genome
RNA, Small Interfering
Sequence Determinations, RNA
Complex (molecular entity)
Parallel Study
Genome Assembly Sequence

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