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Updated: Feb 28, 2026
Generating Acute and Chronic Experimental Models of Motor Tic Expression in Rats
Published on: May 27, 2021
LY294002, a PI3K inhibitor, attenuates Tourette syndrome in rats
Long Hongyan1, Wang Chunyan2, Yang Yue'e3
1Central Laboratory, Nanjing Municipal Hospital of T.C.M., The Third Affiliated Hospital of Nanjing University of T.C.M., Nanjing, 210001, China. longhongyantcm@163.com.
Abstract:
The present study was designed to investigate the effects of LY294002 on Tourette syndrome (TS) in rats. TS model was induced in rats by DOI (the selective 5-HT2A/2C agonist 1- (2, 5- dimethoxy -4 - iodophenyl) -2- aminopropane). Behavior was assessed by stereotypic score and autonomic activity. Inflammatory cytokines such as interleukin-6 (IL-6), interleukin-1β (IL-1β) and tumor necrosis factor-α (TNF-α) in serum and striatum were detected. The protein levels of PI3K/Akt/NF-B in striatum were detected by Western Blot. LY294002 treatment significantly reduced IL-6, IL-1β and TNF-α in serum and striatum of TS rats, Also, highly expressed P-PI3K, P-Akt, P-NF-κBp65, P-IκBα in TS rats were restored respectively by LY294002 treatment as indicted in western blot analysis and immunohistochemistry analysis. Thus, it was supposed that the protective effect of LY294002 against TS in rat might be associated with the regulation of PI3K/Akt/NF-B pathway.
Insights
LY294002 treatment reduced inflammation and normalized key protein levels in a rat model of Tourette syndrome (TS). This suggests LY294002 may offer a protective effect against TS by regulating the PI3K/Akt/NF-κB pathway.
Area of Science:
- Neuroscience
- Pharmacology
- Molecular Biology
Background:
- Tourette syndrome (TS) is a neurological disorder characterized by motor and vocal tics.
- The precise mechanisms underlying TS pathogenesis remain incompletely understood.
- The PI3K/Akt/NF-κB signaling pathway is implicated in neuroinflammation and neuronal function.
Purpose of the Study:
- To investigate the therapeutic potential of LY294002, a PI3K inhibitor, in a rat model of Tourette syndrome.
- To elucidate the effects of LY294002 on behavioral symptoms, inflammatory markers, and the PI3K/Akt/NF-κB pathway in TS rats.
Main Methods:
- A Tourette syndrome rat model was established using DOI, a selective 5-HT2A/2C agonist.
- Behavioral assessments included stereotypic scores and autonomic activity monitoring.
- Serum and striatal levels of inflammatory cytokines (IL-6, IL-1β, TNF-α) were measured.
- Protein expression of PI3K/Akt/NF-κB pathway components in the striatum was analyzed using Western Blot and immunohistochemistry.
Main Results:
- LY294002 administration significantly attenuated stereotypic behaviors and autonomic hyperactivity in TS rats.
- Treatment with LY294002 markedly reduced elevated serum and striatal levels of IL-6, IL-1β, and TNF-α.
- LY294002 treatment restored the aberrant phosphorylation of PI3K, Akt, and NF-κB pathway proteins (p-PI3K, p-Akt, p-NF-κBp65, p-IκBα) in the striatum of TS rats.
Conclusions:
- LY294002 demonstrates significant therapeutic effects in a rat model of Tourette syndrome.
- The neuroprotective effects of LY294002 are associated with the modulation of the PI3K/Akt/NF-κB signaling pathway and reduction of neuroinflammation.
- These findings suggest that targeting the PI3K/Akt/NF-κB pathway may be a viable therapeutic strategy for Tourette syndrome.
