Evidence is presented, based on immunoblotting, immunohistochemistry a
nd double immunolabelling procedures, for the existence of hyaluronan
receptor immunoreactivity in discrete nerve cell populations of the ra
t brain, present within the zona compacta and the zona reticulata of t
he substantia nigra, the ventral tegmental area, the locus coeruleus,
the mesencephalic trigeminal nucleus, the nucleus of the trapezoid bod
y, the motor trigeminal nucleus and the lateral cerebellar nucleus. Wi
th preimmune serum control, this hyaluronan receptor immunoreactivity
could not be demonstrated. Double immunofluorescence immunocytochemist
ry, using a well-characterized hyaluronan receptor antiserum, together
with the tyrosine hydroxylase antiserum, in the presence or absence o
f detergent, demonstrated the existence of hyaluronan receptor immunor
eactivity in dopamine nerve cells of the substantia nigra and the vent
ral tegmental area and in noradrenaline nerve cells of the locus coeru
leus, previously shown not to stain for hyaluronan. In all the nerve c
ells, the immunoreactivity had the appearance of punctate bodies mainl
y located in the cytoplasm of the perikarya of the above nerve cell po
pulations as also shown by confocal laser microscopy in the mesencepha
lic trigeminal nucleus. Based on these observations, it is concluded t
hat hyaluronan receptors exist in discrete nerve cell populations of t
he brain, including many noradrenaline and dopamine neurones. In all n
erve cells, it is located intracellularly in bodies possibly represent
ing clustered hyaluronan receptors undergoing endocytosis. The results
open up the possibility that hyaluronan receptors may reduce high con
centrations of hyaluronic acid in the surrounding matrix, thereby faci
litating communication between adjacent neurones. Intracytoplasmatic h
yaluronic acid may also be of special importance for neuronal plastici
ty, in view of the ability of hyaluronic acid to activate protein kina
se activity and/or by influencing the architecture of the cytoskeleton
.