In vivo expression of the intermediate filament peripherin in rat motoneurons: Modulation by inhibitory and stimulatory signals

Peripherin is a type III intermediate filament which, in contrast to the ne urofilaments, is strongly up-regulated after nerve injury. Although periphe rin expression is stimulated irt vitro by neurotrophins and cytokines, litt le is known about its in vivo regulation. In this report, we show that the in vivo down-regulation of peripherin expression to normal levels during re generation closely correlates with target reconnection in rat facial motone urons. Prevention of reconnection, by transection and suture, results in th e persistence of strong peripherin expression for prolonged periods of up t o 11 months. This contrasts with the modulation of the p75 low-affinity neu rotrophin receptor, whose expression returns to normal even in the absence of reconnection. We further demonstrate that blockade of the axonal transpo rt in non-injured motoneurons increases the expression of peripherin. Block ade of the axonal transport simultaneously to, or after injury of, facial m otoneurons does not abolish the axotomy-induced peripherin up-regulation. These data demonstrate that the in vivo expression of peripherin is normall y restrained by a distal retrogradely transported inhibitory signal. Thus, peripherin up-regulation results primarily from a lack of supply in this fa ctor. Our results show that stimulatory factors released at the injury site are not required for the initial up-regulation and maintenance of high per ipherin expression. However, they appear to enhance this increase during th e acute post-lesion phase. Peripherin expression is thus finely tuned by bo th glial cell-derived stimulatory and distal inhibitory signals that reflec t neuron-target interactions. (C) 2000 IBRO. Published by Elsevier Science Ltd. All rights reserved.