N-methyl-d-aspartate receptor is involved in the progression of anxiety disorders with thyroid tumors

Anxiety disorders (ADs) and thyroid tumors (TTs) are prevalent and frequently co-occur. Previous studies suggest that the N-methyl-d-aspartate receptor (NMDAR) may play a role in their co-occurrence, but the understanding of their relationship is not comprehensive. The aim of this study was to investigate the role of NMDAR in the progression of animal models of AD with TT.

We developed an animal model of AD with TT in Balb/c mice using chronic unpredictable mild stress (CUMS) combined with subcutaneous IHH4 cell xenotransplantation. Mice were treated with d-serine and MK-801 to assess behavioral changes and tumor growth. The expression of NMDAR subunits in the thyroid and transplanted TT tissues was also analyzed.

The combination of CUMS and IHH4 cell xenotransplantation helped successfully create an AD with TT model, which exhibited stable anxiety-like behavior, a high tumor formation rate, and ease of implementation. d-Serine alleviated anxiety behaviors but increased NR2A subunit activity in both thyroid and TT tissues, disrupted the normal structure of the thyroid, and accelerated TT growth. In contrast, MK-801 had the opposite effect.

NMDAR, particularly the NR2A subunit, plays a crucial role in TT progression associated with AD. In the clinical drug selection for the patients with ADs with concomitant TT, special attention should be paid to the two-sidedness of drugs. The CUMS and IHH4 xenotransplantation model is an effective tool for studying AD with TT.