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Involvement of glucose related energy crisis and endoplasmic reticulum stress: Insinuation of streptozotocin induced Alzheimer's like pathology.

Authors: Biswas, Joyshree  Gupta, Sonam  Verma, Dinesh Kumar  Gupta, Parul  Singh, Abhishek  Tiwari, Shubhangini  Goswami, Poonam  Sharma, Sharad  Singh, Sarika 
Citation: Biswas J, etal., Cell Signal. 2018 Jan;42:211-226. doi: 10.1016/j.cellsig.2017.10.018. Epub 2017 Nov 7.
Pubmed: (View Article at PubMed) PMID:29126976
DOI: Full-text: DOI:10.1016/j.cellsig.2017.10.018

The present study was conducted to correlate the cellular and molecular alterations in Alzheimer's pathology employing streptozotocin (STZ) induced experimental rat model. The STZ was administered in rat brain bilaterally by intracerebroventricular route using stereotaxic surgery followed by donepezil dosing. The Alzheimer's related pathological marker like acetylcholinesterase (AChE) activity, tau phosphorylation and amyloid aggregation were observed after STZ administration. STZ treatment showed decreased glucose and glucose transporters (GLUT) level along with augmented level of calcium in both cortical and hippocampal regions of rat brain. Increased calcium level may correlate with endoplasmic reticulum (ER) stress and significantly increased expression of ER stress markers like GRP78, GADD and caspase-12 were observed in STZ treated rat brain. Cellular communication was also affected by STZ administration as observed by increased expression connexin 43. With this view the activation of astrocytes and microglia was also assessed and observed by augmented GFAP and cd11b expression which were partially inhibited with donepezil treatment. The significantly increased level of degenerating neurons, caspase-3 and DNA fragmentation was also observed in rat brain regions which were not inhibited with donepezil treatment and validating the clinical observations. In conclusion, study indicated the STZ induced occurrence of Alzheimer's pathology. Further, STZ administration also caused depleted glucose level, inhibited mitochondrial activity, augmented calcium levels, ER stress, altered cellular communication and neuronal death which were partially attenuated with donepezil treatment.


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RGD Object Information
RGD ID: 13782165
Created: 2018-08-24
Species: All species
Last Modified: 2018-08-24
Status: ACTIVE


RGD is funded by grant HL64541 from the National Heart, Lung, and Blood Institute on behalf of the NIH.