الفهرس 
The Possible Neuroprotective Effect of Dapagliflozin in 3-Nitropropinic Acid-induced Huntington’s disease in Rats
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Abstract
Aims: Huntington‟s disease (HD) is a rare neurodegenerative disorder which is associated with
defected glucose metabolism with consequent behavioral disturbance including memory and
locomotion. 3-nitropropionic acid (3-NP) can cause, in high single dose, an acute striatal injury/
Huntington‟s disease. Dapagliflozin, which is one of the longest duration of action of
Sodium‐Glucose Cotransporter Inhibitors (SGLTIs) family, may be able to diminish that injury
and its resultant behavioral disturbances.
Material and methods: Forty rats were divided into four groups (n = 10 in each group): Normal
control group (CTRL), Dapagliflozin (CTRL+DAPA) group, 3-nitropropionic acid (3-NP)
group, and dapagliflozin plus 3-nitropropionic acid (DAPA+3-NP) group. Behavioral tests (beam
walking test, hanging wire test, limb withdrawal test, Y-maze spontaneous alteration, elevated
plus maze) were performed with evaluating neurological scoring. In striatum, neurotransmitters
(glutamate, aspartate, GABA, ACh and AChE activity) were measured. In addition, apoptosis
and glycolysis markers (NF-κB, Cyt-c, lactate, HK-II activity, P53, calpain, PEA15 and TIGAR)
were determined. Inflammation (IL-1β, IL-6, IL-8 and TNF-α) and autophagy (beclin-1, LC3
and DRAM) indicators were measured. Additionally, histopathological screening was conducted.
Key findings: 3-NP had the ability to perturb the neurotransmission which was reflected in
impaired behavioral outcome. All of glycolysis, apoptosis and inflammation markers were
elevated after 3-NP acute intoxication but autophagy parameters, except DRAM, were reduced.
However, DAPA markedly reversed the abovementioned parameters.
Significance: Dapagliflozin demonstrated anti-glycolytic, anti-apoptotic, anti-inflammatory and
autophagic effects on 3-NP-damaged striatal cells and promoted the behavioral outcome