Implication of JAK1/STAT3/SOCS3 Pathway in Aging of Cerebellum of Male Rat: Histological and Molecular study

Enas Ahmed Mohamed,Walaa Mohamed Sayed

doi:10.1038/s41598-020-64050-z

Enas Ahmed Mohamed, Walaa Mohamed Sayed

Open Access

https://doi.org/10.1038/s41598-020-64050-z

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Journal: Scientific Reports	Publication Date: Jun 1, 2020
Citations: 5	License type: open-access

Affiliation: Cairo University, Qassim University

Abstract

Aging causes morphological and functional changes in the cerebellum. This work aimed to demonstrate the implication of JAK1/STAT3/SOCS3 on aging–induced changes of rat cerebellum. Thirty male rats were divided into: adult (12 months), early senile (24 months) and late senile (32 months) groups. Immunohistochemical reaction of the cerebellum to GFAP and caspase-3 was assessed and the expression of JAK1, STAT3, SOCS3 proteins was also evaluated. TNFα as well as the activities of malondialdehyde (MDA) and reduced glutathione (GSH) in cerebellar tissue were also measured. The cerebellum of late senile rats revealed more degenerative changes than early senile rats in the form of increase in GFAP and caspase-3 immunoreaction. Additionally, there was decrease in JAK1and STAT3 expression in early and late senile rats and increase in SOCS3 when compare early and late senile groups with adult one. Enhancement of TNFα was noticed with aging as well as significant decrease in GSH and increase in MDA in early senile group. Moreover, late senile group revealed significant decrease in GSH and increase in MDA. It could be concluded that aging resulting in variable changes of the cerebellum as detected by morphological changes, immunohistochemical reactions of caspase-3 and GFAP and expression of JAK1/STAT3/SOCS3 proteins. Additionally, inflammatory marker TNFα and the activity of oxidative/antioxidative stress markers; malondialdehyde (MDA) and reduced glutathione (GSH) were also affected with aging.

Highlights

The cerebellum is a fundamental part of the brain that is responsible for movement and awareness activities, such as training of motor activity, recognition of time and fine movements[1]
The present study aimed to demonstrate the impact of JAK1/STAT3/SOCS3 signaling link on the age-related histological and ultrastructural changes of the cerebellar cortex of male rat
Microscopic examination of H&E-stained cerebellar tissue showed that early senile rats exhibited degenerative changes including damaged purkinjie cells which were surrounded with vacuolated neuropil, areas of complete disappearance of purkinjie cells, and vacuolated areas in the molecular layer

Summary

Introduction

The cerebellum is a fundamental part of the brain that is responsible for movement and awareness activities, such as training of motor activity, recognition of time and fine movements[1]. The cerebellar cortex acts for designing motor functions, storing memories and adapting some behaviors, so it is the focus of the different research aspects including structural morphology, components of nerve cell and connections of fibers[2]. Astrogliosis or gliosis is an astroglial proliferation that is accompanied by several brain injuries including aging and the regulation of gliosis is related to changes in GFAP expression[4]. Caspase-3 is mediated by death receptor on the cell surface and mitochondrial apoptosis pathways[5,6]. Signal transducers-Janus kinase (JAK) and transcription activators (STAT) are newly discovered proteins that their intracellular signaling pathway affects the replication of DNA and presentation of genetic material that are included in cellular stimulation, multiplication, immunological reactions and programmed cell death. The different types of JAK and STAT www.nature.com/scientificreports are presented in many regions of the central nervous system, like cerebrum, hippocampal tissue and cerebellar cortex[8]

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