Evidence for receptors for hyaluronan in discrete nerve cell populations of the brain

Evidence is presented, based on immunoblotting, immunohistochemistry and double immunolabelling procedures, for the existence of hyaluronan receptor immunoreactivity in discrete nerve cell populations of the rat brain, present within the zona compacta and the zona reticulata of the substantia nigra, the ventral tegmental area, the locus coeruleus, the mesencephalic trigeminal nucleus, the nucleus of the trapezoid body, the motor trigeminal nucleus and the lateral cerebellar nucleus. With preimmune serum control, this hyaluronan receptor immunoreactivity could not be demonstrated. Double immunofluorescence immunocytochemistry, using a well-characterized hyaluronan receptor antiserum, together with the tyrosine hydroxylase antiserum, in the presence or absence of detergent, demonstrated the existence of hyaluronan receptor immunoreactivity in dopamine nerve cells of the substantia nigra and the ventral tegmental area and in noradrenaline nerve cells of the locus coeruleus, previously shown not to stain for hyaluronan. In all the nerve cells, the immunoreactivity had the appearance of punctate bodies mainly located in the cytoplasm of the perikarya of the above nerve cell populations as also shown by confocal laser microscopy in the mesencephalic trigeminal nucleus. Based on these observations, it is concluded that hyaluronan receptors exist in discrete nerve cell populations of the brain, including many noradrenaline and dopamine neurones. In all nerve cells, it is located intracellularly in bodies possibly representing clustered hyaluronan receptors undergoing endocytosis. The results open up the possibility that hyaluronan receptors may reduce high concentrations of hyaluronic acid in the surrounding matrix, thereby facilitating communication between adjacent neurones. Intracytoplasmatic hyaluronic acid may also be of special importance for neuronal plasticity, in view of the ability of hyaluronic acid to activate protein kinase activity and/or by influencing the architecture of the cytoskeleton.