Role Of Astrocytes On Neuronal Health In Models Of Alzheimer’s Disease
IR@IICB: CSIR-Indian Institute of Chemical Biology, Kolkata
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| Title |
Role Of Astrocytes On Neuronal Health In Models Of
Alzheimer’s Disease
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| Creator |
GUHA, SUBHALAKSHMI
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| Subject |
Cell Biology & Physiology
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| Description |
Alzheimer’s disease (AD), one of the major forms of dementia in elderly population, is characterized by amyloid beta (Aβ) plaque along with commonly procured tau hyperphosphorylation. Here, we set to recognize the molecules which are secreted by Aβ1-42 treated astrocytes at very early stage and their probable role in conferring neuroprotection along with improvement in cognitive behavior and pathogenesis of AD. Astrocyte activation has been marked by various specific marker proteins like GFAP, Vimentin, S100β. The conditioned medium obtained from the astrocytes cultured from neonatal pups has been used to check the differential expression of various cytokines in Aβ42 treated astrocytes as compared to control cells. From there soluble intercellular adhesion molecule-1 (sICAM-1) has been noted as a potential candidate. We observed that sICAM-1 protects the cortical neurons from death influenced by Aβ42 oligomers. It attenuates the PARP cleavage caused by Aβ42 and increases the amount of anti-apoptotic proteins such as Bcl-2 and Bcl-xL, along with decrease in the amount of pro-apoptotic protein Bim. TUNEL assay performed both in cortex and hippocampus of Aβ42 infused rat brain and 5xFAD mice brain showed that rrICAM-1 treatment reduced the number of TUNEL positive cells in vivo. Several behavioral experiments namely open field test, contextual and cue dependent fear conditioning, passive avoidance tests, novel object recognition and elevated plus maze that can be related to multiple kinds of memory and learning have displayed that rat recombinant ICAM-1 on being injected within the system intraperitoneally, restored the malfunctioning in the rat behavior caused due to bilateral Aβ42 infusion. We took further interest in checking the underlying disease modifying mechanism rendered by ICAM-1 both in vitro and in vivo systems which might be considered being a therapeutic target for neuroprotection. Mechanistically we observed that ICAM-1 administration decreases NF-κB protein level in AD pathology suggesting that ICAM-1 might play a crucial role in manipulating the stability of NF-κB through multiple degradation process. Also PDTC mediated inhibition of NF-κB protein in 5xFAD transgenic mice brain showed an improvement in cognitive behaviors including learning and memory in mice. Therapeutic approach towards prevalent neurodegenerative diseases like AD is one of the major concerns in the scientific world. Our work suggests that ICAM-1 protein could be said as a potential therapeutic agent that promotes neuronal protection along with recovery in cognitive functioning complemented with clearance of Aβ in Aβ42 infused rats and 5xFAD mice model of AD.
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| Date |
2021
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| Type |
Thesis
NonPeerReviewed |
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| Format |
application/pdf
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| Identifier |
http://www.eprints.iicb.res.in/2830/1/Thesis_for_evaluation_Subhalakshmi_Guha.pdf
GUHA, SUBHALAKSHMI (2021) Role Of Astrocytes On Neuronal Health In Models Of Alzheimer’s Disease. PhD thesis, UNIVERSITY OF CALCUTTA. |
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| Relation |
http://www.eprints.iicb.res.in/2830/
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