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...
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Elsevier
2020-11-01
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Series: | Comprehensive Psychoneuroendocrinology |
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Online Access: | http://www.sciencedirect.com/science/article/pii/S2666497620300199 |
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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. |
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issn | 2666-4976 |
language | English |
last_indexed | 2024-12-19T06:19:21Z |
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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 |
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