Loss of Slc39a12 in hippocampal neurons is responsible for anxiety-like behavior caused by temporomandibular joint osteoarthritis

Abstract

Background

An evident association between mood disorders and TMJ dysfunction has been demonstrated in previous studies. This study observed both the behavioral changes and the pathological changes in hippocampal tissue of rats in an animal model of TMJ-OA by injecting MIA into TMJ.

Methods

Eighteen SD rats were randomly assigned to the NC group and the MIA groups. A TMJ-OA model was established to assess the HWT in the TMJ region, and the rats were subjected to the OFT and EPM. HE, O-fast green staining, qRT-PCR and immunofluorescence were used to detect condylar damage. Serum and hippocampal oxidative stress levels were detected. Functions of genes obtained by RNA-Seq were investigated using H ₂O ₂, ZnCl ₂ and transfection of siRNA on HT22 cells.

Results

Injection of MIA resulted in disorganization of the chondrocyte layer on the condylar surface of rats, with reduced synthesis and increased degradation of the condylar cartilage matrix and reduced HWT. The results of the OFT and EPM showed that the rats in the MIA group developed anxiety-like behavior during the sixth week of MIA injection. Increased Nox4 expression, decreased SOD2 expression, elevated MDA level, and reduced GSH level were detected in serum and hippocampal neurons in the MIA group, with nuclear pyknosis and reduced Nissl bodies observed in neurons. The expression of Slc39a12 in hippocampal neurons of rats in the MIA group decreased. Slc39a12 knockdown in HT22 cells induced increased Nox4 expression, decreased SOD2 expression, increased MDA level, and reduced GSH and intracellular Zn ²⁺. Oxidative stress in HT22 cells after transfection and H ₂O ₂ stimulation was reversed when ZnCl ₂ was added.

Conclusion

Loss of Slc39a12 in hippocampal neurons results in cellular oxidative stress, further leading to neuronal damage. This may potentially explain how TMJ-OA triggers anxiety-like behavior in rats.

Graphical abstract

Highlights

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  TMJ-OA causes anxiety-like behavior in rats.

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  TMJ-OA leads to neuronal damage in hippocampus of rats.

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  Elevated oxidative stress due to reduced Slc39a12 expression is responsible for neuronal damage.

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  This study presents pathophysiological evidence of anxiety induced by TMJ-OA.