Prosaposin is the precursor for saposins A, B, C, and D, which are sma
ll lysosomal proteins required for the hydrolysis of sphingolipids by
specific lysosomal hydrolases. With a monospecific anti-saposin C anti
body, which cross-reacts with prosaposin but not with saposin A, B, or
D, the present immunoblot experiments showed that the rat brain expre
sses an unprocessed approximately 72 kDa protein (possibly prosaposin)
and little saposin C. Regional analysis demonstrated that prosaposin
is abundant in the brainstem, hypothalamus, cerebellum, striatum, and
hippocampus, and less abundant in the cerebral cortex. Consistent with
this finding, prosaposin-like immunoreactive neurons and fibers as re
vealed by immunohistochemistry were observed frequently in subcortical
regions. The medial septum, diagonal bands, basal nucleus of Meynert,
ventral striatum, medial habenular nucleus, and motor nuclei of crani
al nerve had significant numbers of immunoreactive neurons. There were
also nerve fibers with prosaposin-like immunoreactivity in several pr
ojection fields of the above nuclei. Other brain areas that contained
prosaposin-like immunoreactive neurons and/or processes were: several
brain nuclei (nucleus caudate putamen, globus pallidus, substantia nig
ra, red nucleus) constituting the so-called extrapyramidal system, ret
icular thalamic nucleus, entopeduncular nucleus, mammillary nuclei, au
ditory relay nuclei, cerebellum, sensory cranial nerve nuclei, and the
reticular formation. The distribution pattern of prosaposin is appare
ntly different from that of other neuroactive substances so far examin
ed, and thus prosaposin may be involved in novel central events. (C) 1
993 Wiley-Liss, Inc.