Reactive astrocyte formation in vivo is regulated by noradrenergic axons.

Beta adrenergic receptor antagonists greatly reduce reactive astrocyte formation induced by neuronal degeneration. To test the hypothesis that the density of noradrenergic innervation is a factor in the regulation 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 communis lectin into a cranial or peripheral nerve to destroy CNS neurons without the blood-brain barrier disruption and lymphocyte infiltration associated with contusive or surgical lesions. We took advantage of the lack of an NE transporter in the terminals of certain classes of noradrenergic axons to produce noradrenergic sprouting in the trigeminal motor nucleus (MoV) with neonatal 6-hydroxydopamine (6-OHDA) treatment and to produce depletion of NE in the spinal cord dorsal horn with N-(2-chloroethyl)-N-ethyl-2-bromobenzylamine hydrochloride (DSP-4) administration. In each of these regions, GFAP optical density in the region of reactive astrocytes on the Ricin lectin-treated side was compared with the untreated contralateral (control) side in animals with NE hyperinnervation 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 formation 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-adrenergic receptor blockade reduces reactive astrocyte formation, these data indicate that the noradrenergic innervation is a factor in the degree of astrocyte reactivity following injury.