Immunohistochemical Localization of MD2, a Co-Receptor of TLR4, in the Adult Mouse Brain.

Myeloid differentiation factor 2 (MD2) is a co-receptor of a classical proinflammatory protein TLR4 whose activation leads to neuroinflammation. It is widely accepted that TLR4 is expressed on the cell surface of microglia and astrocytes, and MD2 is expected to be expressed by these cells as well. However, our previous study showed that neurons from certain nuclei also expressed MD2. Whether MD2 is expressed by other brain nuclei is still unknown. It is the aim of the present study to map the distribution of MD2-positive cells in the adult mouse brain. Immunohistochemical staining against MD2 was completed to localize MD2-positive cells in the mouse brain by comparing the location of positive cells with the mouse brain atlas. MD2-positive cells were found in the majority of mouse brain nuclei with clusters of cells in the olfactory bulb, cortices, the red nucleus, and cranial nuclei. Subcortical nuclei had heterogeneous staining of MD2 with more prominent cells in the basolateral and the central amygdaloid nuclei. The ventral pallidum and the diagonal bands had positive cells with similar density and shape. Prominent cells were present in thalamic nuclei which were nearly homogeneous and in reticular formation of the brainstem where cells were dispersed with similar density. The hypothalamus had fewer outstanding cells compared with the thalamus. The red nucleus, the substantia nigra, and the ventral tegmental area in the pretectum had outstanding cells. Motor cranial nuclei also had outstanding MD2-positive cells, whereas raphe, sensory cranial, and deep cerebellar nuclei had MD2-positive cells with moderate density. The presence of MD2 in these nuclei may suggest the involvement of MD2 in their corresponding physiological functions.