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.