R. Griffith et J. Sutin, REACTIVE ASTROCYTE FORMATION IN-VIVO IS REGULATED BY NORADRENERGIC AXONS, Journal of comparative neurology, 371(3), 1996, pp. 362-375
Beta adrenergic receptor antagonists greatly reduce reactive astrocyte
formation induced by neuronal degeneration. To test the hypothesis th
at the density of noradrenergic innervation is a factor in the regulat
ion of astrocytosis, we measured glial fibrillary acidic protein (GFAP
) optical density after neuronal injury in central nervous system (CNS
) regions with permanent noradrenergic sprouting or norepinephrine (NE
) depletion. The injury model employs the injection of Ricinus communi
s lectin into a cranial or peripheral nerve to destroy CNS neurons wit
hout the blood-brain barrier disruption and lymphocyte infiltration as
sociated with contusive or surgical lesions. We took advantage of the
lack of an NE transporter in the terminals of certain classes of norad
renergic axons to produce noradrenergic sprouting in the trigeminal mo
tor nucleus (MoV) with neonatal 6-hydroxydopamine (6-OHDA) treatment a
nd to produce depletion of NE in the spinal cord dorsal horn with N-(2
-chloroethyl)-N-ethyl-2-bromobenzylamine hydrochloride (DSP-4) adminis
tration. In each of these regions, GFAP optical density in the region
of reactive astrocytes on the Ricin lectin-treated side was compared w
ith the untreated contralateral (control) side in animals with NE hype
rinnervation or NE depletion. GFAP density was increased about 55% in
the injured NE-hyperinnervated MoV and was decreased about 35% in the
injured NE-depleted dorsal horn. The degree of reactive astrocyte form
ation to injury is known to vary in different regions of the CNS, and
our results suggest that differences in noradrenergic innervation may
contribute to this variation. Along with earlier findings that beta-ad
renergic receptor blockade reduces reactive astrocyte formation, these
data indicate that the noradrenergic innervation is a factor in the d
egree of astrocyte reactivity following injury. (C) 1996 Wiley-Liss, I
nc.