Cerebellar ataxia is a neurodegenerative disorder with no definitive treatment. Although previous study demonstrated the neuroprotective effects of Hericium erinaceus (H.E.), the mechanisms of H.E. treatment on the neuroinflammatory response, neurotransmission, and related metabolites remain largely unknown. We demonstrated that 3-AP rats treated with 25 mg/kg H.E. extracts had improved motor coordination and balance in the accelerated rotarod and rod tests. We showed that the H.E. treatment upregulated the expression of Tgfb1, Tgfb2, and Smad3 genes to levels comparable to those in the non-3-AP control group. Interestingly, we also observed a significant correlation between Tgfb2 gene expression and rod test performance in the 3-AP saline group, but not in the non-3-AP control or H.E.+3-AP groups, indicating a relationship between Tgfb2 gene expression and motor balance in the 3-AP rat model. Additionally, we also found that the H.E. treatment increased mitochondrial COX-IV protein expression and normalized dopamine-serotonin neurotransmission and metabolite levels in the cerebellum of the H.E.+3-AP group compared to the 3-AP saline group. In conclusion, our findings suggest that the H.E. treatment improved motor function in the 3-AP rat model, which was potentially mediated through neuroprotective mechanisms involving TGFB2-Smad3 signaling via normalization of neurotransmission and metabolic pathways.

Mice rely heavily on their sense of smell to provide crucial environmental information. The intricate organization of neural circuits within the olfactory bulb (OB) and the communication across the OB-hippocampus network in mice underpin their ability to discriminate and adapt to odors and perform odor-guided behaviors. Wnt/β-catenin signaling has been shown to regulate neural stem cell proliferation and migration during embryogenesis and adult neurogenesis. However, the potential role of β-catenin in adult OB and hippocampus in olfaction, odor-guided behavior and working memory is not known. Here, we report the unexpected expression of collagen, type X, alpha 1 (Col10a1), in the postnatal mouse OB and the hippocampus starting at approximately postnatal day 14. We exploited this finding to generate OB and hippocampus conditional Ctnnb1 knockout (Ctnnb1^cKO) mice. We found Ctnnb1^cKO mice displayed impaired odor habituation and discrimination abilities, whereas food foraging ability was unaffected. Surprisingly, Ctnnb1^cKO mice displayed modestly improved working memory in the Radial Arm Maze test. Together, these findings identify behavioral phenotypes associated with Col10a1-Cre-driven Ctnnb1 deletion and establish this mouse line as a useful tool for studying β-catenin function in adult OB–hippocampal circuits.