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RETRACTED ARTICLE: Intracerebroventricular streptozotocin administration impairs mitochondrial calcium homeostasis and bioenergetics in memory-sensitive rat brain regions

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This article was retracted on 05 September 2023

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Abstract

Alzheimer's disease (AD) is a progressive neurodegenerative disorder with cardinal manifestation of cognitive dysfunction. The limitation to avail a successful drug candidate encourages researchers to establish an appropriate animal model in the novel anti-AD drug discovery process. In this context, the mechanism of mitochondrial dysfunction in cognitive deficit animals is yet to be established for intracerebroventricular injection of streptozotocin (ICV-STZ). Experimental dementia was induced in male rats by ICV-STZ on day-1 (D-1) of the experimental protocol at a sub-diabetogenic dose (3 mg/kg) twice at an interval of 48 h into both rat lateral ventricles. ICV-STZ caused cognitive decline in terms of increase in the escape latency on D-14 to D-17 and, decrease in the time spent and percentage of distance travelled in the target quadrant during Morris water maze and decrease in the spontaneous alteration behavior during Y-maze tests in rats. Further, ICV-STZ decreased the level of acetylcholine and activity of choline acetyltransferase and increased the activity of acetylcholinesterase in rat hippocampus, pre-frontal cortex and amygdala. Interestingly, ICV-STZ increased the mitochondrial calcium in addition to decrease in the mitochondrial function, integrity and bioenergetics in all rat brain regions. Further, ICV-STZ enhanced the levels of expression of NR1 subunit of N-methyl-d-aspartate receptor, mitochondrial calcium uniporter and sodium-calcium exchanger in these rat brain regions. Thus, NR1-dependent mitochondrial calcium accumulation could be considered as a major attribute to the animal model of ICV-STZ-induced AD-like manifestations. Further, drugs targeting to manage mitochondrial calcium homeostasis could best be studied in this animal model.

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Acknowledgements

YS is thankful to GLA University, Mathura, Uttar Pradesh, India for the financial assistantship.

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  1. Division of Pharmacology, Institute of Pharmaceutical Research, GLA University, Mathura, 281 406, India

    Yati Sharma & Debapriya Garabadu

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  1. Yati Sharma
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Sharma, Y., Garabadu, D. RETRACTED ARTICLE: Intracerebroventricular streptozotocin administration impairs mitochondrial calcium homeostasis and bioenergetics in memory-sensitive rat brain regions. Exp Brain Res 238, 2293–2306 (2020). https://doi.org/10.1007/s00221-020-05896-7

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