Differential activation of Gsk-3β in the cortex and the hippocampus induces cognitive and behavioural impairments in middle-aged ovariectomized rat

Glycogen synthase kinase-3 (Gsk-3β) aberration act as a crucial pathogenic factor in several neurological conditions. However its role in menopause associated behavioural impairments is still not unclear. The present study was designed to understand the role of Gsk-3β in the progression of neurobeha...

Full description

Bibliographic Details
Main Authors: Anil Kumar Rana, Supriya Sharma, Damanpreet Singh
Format: Article
Language:English
Published: Elsevier 2020-11-01
Series:Comprehensive Psychoneuroendocrinology
Subjects:
Online Access:http://www.sciencedirect.com/science/article/pii/S2666497620300199
_version_ 1818848564877459456
author Anil Kumar Rana
Supriya Sharma
Damanpreet Singh
author_facet Anil Kumar Rana
Supriya Sharma
Damanpreet Singh
author_sort Anil Kumar Rana
collection DOAJ
description Glycogen synthase kinase-3 (Gsk-3β) aberration act as a crucial pathogenic factor in several neurological conditions. However its role in menopause associated behavioural impairments is still not unclear. The present study was designed to understand the role of Gsk-3β in the progression of neurobehavioural impairments in middle-aged ovariectomized (ovx) rats. The animals showed a significant impairment in spatial and recognition memory, along with anxiety and depression-like behaviour following 22 weeks of ovx. The genomic expression of ERα, ERβ, Nrf2, HO-1, TNFα, and IL-6 was altered in both the cortex and the hippocampus of ovx rats. Protein expression of p-Gsk-3β(Ser9) was significantly downregulated in the cortex after ovx. However, the hippocampus showed a surprisingly opposite trend in the levels of p-Gsk-3β(Ser9) as that of the cortex. Differential activation of Gsk-3β and its downstream proteins such as β-catenin and p-mTOR were also altered following ovx. The study concluded that differential activation of Gsk-3β, along with oxidative stress and neuroinflammation in the cortex and the hippocampus, leads to the induction of cognitive and behaviour impairments in ovx rats.
first_indexed 2024-12-19T06:19:21Z
format Article
id doaj.art-77964ad64c23494aa8b8b479533164a2
institution Directory Open Access Journal
issn 2666-4976
language English
last_indexed 2024-12-19T06:19:21Z
publishDate 2020-11-01
publisher Elsevier
record_format Article
series Comprehensive Psychoneuroendocrinology
spelling doaj.art-77964ad64c23494aa8b8b479533164a22022-12-21T20:32:46ZengElsevierComprehensive Psychoneuroendocrinology2666-49762020-11-014100019Differential activation of Gsk-3β in the cortex and the hippocampus induces cognitive and behavioural impairments in middle-aged ovariectomized ratAnil Kumar Rana0Supriya Sharma1Damanpreet Singh2Pharmacology and Toxicology Laboratory, CSIR-Institute of Himalayan Bioresource Technology, Palampur, 176061, Himachal Pradesh, India; Academy of Scientific and Innovative Research (AcSIR), CSIR-Institute of Himalayan Bioresource Technology, Palampur, 176061, Himachal Pradesh, IndiaPharmacology and Toxicology Laboratory, CSIR-Institute of Himalayan Bioresource Technology, Palampur, 176061, Himachal Pradesh, India; Academy of Scientific and Innovative Research (AcSIR), CSIR-Institute of Himalayan Bioresource Technology, Palampur, 176061, Himachal Pradesh, IndiaPharmacology and Toxicology Laboratory, CSIR-Institute of Himalayan Bioresource Technology, Palampur, 176061, Himachal Pradesh, India; Academy of Scientific and Innovative Research (AcSIR), CSIR-Institute of Himalayan Bioresource Technology, Palampur, 176061, Himachal Pradesh, India; Corresponding author. Pharmacology and Toxicology Laboratory, CSIR-Institute of Himalayan Bioresource Technology, Palampur, 176061, Himachal Pradesh, India.Glycogen synthase kinase-3 (Gsk-3β) aberration act as a crucial pathogenic factor in several neurological conditions. However its role in menopause associated behavioural impairments is still not unclear. The present study was designed to understand the role of Gsk-3β in the progression of neurobehavioural impairments in middle-aged ovariectomized (ovx) rats. The animals showed a significant impairment in spatial and recognition memory, along with anxiety and depression-like behaviour following 22 weeks of ovx. The genomic expression of ERα, ERβ, Nrf2, HO-1, TNFα, and IL-6 was altered in both the cortex and the hippocampus of ovx rats. Protein expression of p-Gsk-3β(Ser9) was significantly downregulated in the cortex after ovx. However, the hippocampus showed a surprisingly opposite trend in the levels of p-Gsk-3β(Ser9) as that of the cortex. Differential activation of Gsk-3β and its downstream proteins such as β-catenin and p-mTOR were also altered following ovx. The study concluded that differential activation of Gsk-3β, along with oxidative stress and neuroinflammation in the cortex and the hippocampus, leads to the induction of cognitive and behaviour impairments in ovx rats.http://www.sciencedirect.com/science/article/pii/S2666497620300199β-cateninDepressionGlycogen synthase kinase-3Mammalian target of rapamycinOxidative stressSpatial memory
spellingShingle Anil Kumar Rana
Supriya Sharma
Damanpreet Singh
Differential activation of Gsk-3β in the cortex and the hippocampus induces cognitive and behavioural impairments in middle-aged ovariectomized rat
Comprehensive Psychoneuroendocrinology
β-catenin
Depression
Glycogen synthase kinase-3
Mammalian target of rapamycin
Oxidative stress
Spatial memory
title Differential activation of Gsk-3β in the cortex and the hippocampus induces cognitive and behavioural impairments in middle-aged ovariectomized rat
title_full Differential activation of Gsk-3β in the cortex and the hippocampus induces cognitive and behavioural impairments in middle-aged ovariectomized rat
title_fullStr Differential activation of Gsk-3β in the cortex and the hippocampus induces cognitive and behavioural impairments in middle-aged ovariectomized rat
title_full_unstemmed Differential activation of Gsk-3β in the cortex and the hippocampus induces cognitive and behavioural impairments in middle-aged ovariectomized rat
title_short Differential activation of Gsk-3β in the cortex and the hippocampus induces cognitive and behavioural impairments in middle-aged ovariectomized rat
title_sort differential activation of gsk 3β in the cortex and the hippocampus induces cognitive and behavioural impairments in middle aged ovariectomized rat
topic β-catenin
Depression
Glycogen synthase kinase-3
Mammalian target of rapamycin
Oxidative stress
Spatial memory
url http://www.sciencedirect.com/science/article/pii/S2666497620300199
work_keys_str_mv AT anilkumarrana differentialactivationofgsk3binthecortexandthehippocampusinducescognitiveandbehaviouralimpairmentsinmiddleagedovariectomizedrat
AT supriyasharma differentialactivationofgsk3binthecortexandthehippocampusinducescognitiveandbehaviouralimpairmentsinmiddleagedovariectomizedrat
AT damanpreetsingh differentialactivationofgsk3binthecortexandthehippocampusinducescognitiveandbehaviouralimpairmentsinmiddleagedovariectomizedrat