Anxiety and Cognition in Cre- Collagen Type II Sirt1 K/O Male Mice.

Biana Shtaif,Michal Yackobovitch-Gavan,Galia Gat-Yablonski,Moshe Phillip,Shay Henry Hornfeld

doi:10.3389/fendo.2021.756909

Biana Shtaif, Michal Yackobovitch-Gavan + Show 3 more

Open Access

https://doi.org/10.3389/fendo.2021.756909

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Abstract

IntroductionUsing transgenic collagen type II-specific Sirt1 knockout (CKO) mice we studied the role of Sirt1 in nutritional induced catch up growth (CUG) and we found that these mice have a less organized growth plate and reduced efficiency of CUG. In addition, we noted that they weigh more than control (CTL) mice. Studying the reason for the increased weigh, we found differences in activity and brain function.MethodsSeveral tests for behavior and activity were used: open field; elevated plus maze, Morris water maze, and home cage running wheels. The level of Glu- osteocalcin, known to connect bone and brain function, was measured by Elisa; brain Sirt1 was analyzed by western blot.ResultsWe found that CKO mice had increased anxiety, with less spatial memory, learning capabilities and reduced activity in their home cages. No significant differences were found between CKO and CTL mice in Glu- osteocalcin levels; nor in the level of brain SIRT1.Discussion/ConclusionUsing transgenic collagen type II-specific Sirt1 knockout (CKO) mice we found a close connection between linear growth and brain function. Using a collagen type II derived system we affected a central regulatory mechanism leading to hypo activity, increased anxiety, and slower learning, without affecting circadian period. As children with idiopathic short stature are more likely to have lower IQ, with substantial deficits in working memory than healthy controls, the results of the current study suggest that SIRT1 may be the underlying factor connecting growth and brain function.

Highlights

Using transgenic collagen type II-specific sirtuin 1 (Sirt1) knockout (CKO) mice we studied the role of Sirt1 in nutritional induced catch up growth (CUG) and we found that these mice have a less organized growth plate and reduced efficiency of CUG
We found that Sirt1 knockout (CKO) mice have reduced activity, increased anxiety and decreased spatial learning and memory, compared to CTL mice
In a previous study [8], we found that the transgenic collagen type II-specific Sirt1 knockout (CKO) mice had shorter bones with less organized epiphyseal growth plate (EGP), had increased weight, reduced bone mineralization and were less responsive to the nutritional manipulation, with less efficient CUG

Summary

Introduction

Using transgenic collagen type II-specific Sirt knockout (CKO) mice we studied the role of Sirt in nutritional induced catch up growth (CUG) and we found that these mice have a less organized growth plate and reduced efficiency of CUG. Studying the reason for the increased weigh, we found differences in activity and brain function. In order to identify novel regulatory mechanisms in children’s growth, we have been focusing on the epiphyseal growth plate (EGP) and the important role of SIRT1 in regulating the nutrition-growth connection was unraveled [1, 2]. The expression and activity of SIRT1 are tightly regulated. SIRT1 is usually localized to the nucleus but may translocate to the cytosol [3]. It interacts and deacetylates histones and non-histone proteins such as p53, E2F1, NF-kB, and FOXO [4, 5] and through them affects cell proliferation, senescence, autophagy, stress responses, and apoptosis. SIRT1 has been shown to have a substantial role in longevity [6], response to food restriction [1, 7], and linear growth [1, 2]

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