Qufeng Zhidong Recipe attenuates dendritic impairments via GDNF modulation in tourette syndrome: Evidence from clinical and animal studies.

Abstract

ETHNOPHARMACOLOGICAL RELEVANCE: Tourette Syndrome (TS) is a neurodevelopmental disorder marked by motor and vocal tics. Recent evidence highlights the role of neurotrophic factors like glial cell line-derived neurotrophic factor (GDNF), which may play a key role in the pathogenesis and exacerbation of TS. Qufeng Zhidong Recipe (QFZDR), a traditional Chinese herbal formulation, has demonstrated clinical efficacy in the treatment of TS. However, its potential to enhance neurotrophic support and the underlying molecular mechanisms remain unclear. AIM OF THE STUDY: This study aimed to investigate whether the GDNF signaling pathway is involved in the protective effects of QFZDR against dendritic impairments, proposing a new potential therapeutic mechanism for TS. MATERIALS AND METHODS: Clinical and animal studies were conducted to investigate the underlying mechanisms of QFZDR in TS. In the clinical study, serum levels of GDNF and scores on the Yale Global Tic Severity Scale (YGTSS) were assessed before and after QFZDR treatment. In the animal study, the effects of QFZDR on dendritic architecture were evaluated and the expression levels of GDNF, GFRα1, and NCAM1 in the dorsolateral striatum (DLS) were further examined. RESULTS: In patients with TS, serum GDNF levels were significantly lower than those of healthy controls and negatively correlated with tic severity, QFZDR treatment reversed these abnormalities. In animal models, QFZDR attenuates dendritic impairments, and upregulated the expression of GDNF, GFRα1, and NCAM1 in the dorsolateral striatum, suggesting a possible involvement of neurotrophic modulation in its underlying therapeutic mechanism. CONCLUSIONS: QFZDR attenuates tic severity in TS by ameliorating dendritic deficits, which is driven by restoration of the GDNF/GFRα1/NCAM1 pathway, thereby supporting neurotrophic modulation as a potential therapeutic mechanism.