Journal of Neuroscience, Vol 4, 1535-1548, Copyright © 1984 by Society for Neuroscience
Neonatal 6-hydroxydopamine treatment eliminates cholinergic sympathetic innervation and induces sensory sprouting in rat sweat glands
ML Yodlowski, JR Fredieu and SC Landis
Previous studies of the development of cholinergic sympathetic innervation
of sweat glands in rat footpads suggested that these terminals initially
exhibit noradrenergic properties which are lost as the glands and their
innervation mature. We have treated neonatal and adult rats with
6-hydroxydopamine (6-OHDA), a toxic congener of norepinephrine, and
compared its effects on the cholinergic sympathetic innervation of sweat
glands and the noradrenergic sympathetic innervation of the iris, salivary
gland, and blood vessels. As reported by others, 6-OHDA treatment of
neonates caused the destruction of noradrenergic fibers in the iris and
salivary gland but did not affect other fibers projecting to these targets
that stain for acetylcholinesterase (AChE). We found that 6-OHDA treatment
of neonatal animals also caused the destruction of the sympathetic axons in
immature sweat glands that possess catecholamine histofluorescence and
tyrosine-hydroxylase-like immunoreactivity. Furthermore, when such animals
were examined as adults, we found no AChE staining, vasoactive intestinal
peptide (VIP)-like immunoreactivity, or characteristic sympathetic axonal
varicosities. However, the denervated glands were invested by a plexus of
sensory axons, some of which exhibited substance P-like immunoreactivity
(SP-IR). An increase in the number of SP-IR fibers also occurred in the
sympathetically denervated irides of these animals. Chronic treatment of
neonates with guanethidine, another adrenergic sympathetic neurotoxin,
resulted in similar loss of cholinergic sweat gland innervation. Treatment
of adults rats with doses of 6-OHDA identical to those used to treat
neonates caused the loss of noradrenergic fibers from the iris, salivary
gland, and many blood vessels but did not noticeably affect AChE and VIP
staining or axonal ultrastructure in the sweat glands. However, treatment
with higher doses of 6-OHDA did cause significant axonal degeneration. The
response of the sympathetic innervation of developing but not mature sweat
glands to 6-OHDA provides evidence for a transition from noradrenergic to
cholinergic phenotype during the development of sympathetic neurons in vivo
similar to the transition observed in cell culture. The sprouting of
sensory axons may be caused by NGF-like trophic influences present in some
sympathetically denervated tissues.
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