Salidroside enhances hippocampal neurogenesis in a valproic acid-induced mouse model of autism by suppressing neuroinflammation.
TL;DR
Findings suggest that SLDS represents a promising therapeutic candidate for ASD by mitigating neuroinflammation and restoring hippocampal function, given that these observations are derived from preclinical models.
Abstract
Objective
Neuroinflammation plays a pivotal role in the pathogenesis of autism spectrum disorder (ASD) and represents a potential therapeutic target. Salidroside (SLDS), a bioactive compound isolated from Rhodiola rosea L., exhibits potent anti-inflammatory and neuroprotective effects in various neurological disorders; however, its therapeutic efficacy in ASD remains to be fully established. This study investigated whether SLDS ameliorates autism-like behaviors and hippocampal neuroinflammation in a valproic acid (VPA)-induced mouse model.
Methods
A total of 92 male C57BL/6 J mice were randomly assigned to four groups (n = 23 per group). Mice received a subcutaneous injection of VPA or saline on postnatal day 14 (P14), followed by intraperitoneal administration of SLDS or saline from postnatal day 28 (P28) for seven consecutive days. Behavioral assessments were conducted at 8 weeks of age. Hippocampal neuroinflammation, microglial polarization, and neurogenesis were analyzed by molecular, immunofluorescence, and histological techniques.
Results
VPA-exposed mice exhibited social interaction deficits, increased repetitive behaviors, elevated levels of pro-inflammatory cytokines, upregulated expression of inflammation-related proteins, microglial activation, and impaired hippocampal neurogenesis. SLDS treatment significantly attenuated these VPA-induced abnormalities.
Conclusion
Collectively, these findings suggest that SLDS represents a promising therapeutic candidate for ASD by mitigating neuroinflammation and restoring hippocampal function. Nevertheless, given that these observations are derived from preclinical models, further validation in translationally relevant experimental systems and clinical investigations is warranted before extrapolation to human therapeutic applications.