Increase in fiber density for immunoreactive serotonin, substance P, enkephalin and thyrotropin-releasing hormone occurs during the early presymptomatic period of motoneuron disease in Wobbler mouse spinal cord ventral horn

The Wobbler mouse is a useful small animal model for the study of human mot oneuron diseases. Besides showing the loss of motoneurons when the symptoms are expressed around the age of 3 weeks, we have also demonstrated the pre sumed 'sprouting' of neuronal processes in the cervical spinal ventral horn which contain immunoreactive (IR) serotonin (5-HT), substance P (SP) and m ethionine and leucine enkephalins (ME, LE), as well as thyrotropin-releasin g hormone (TRH). This occurs during the symptomatic period when IR-5-HT, ME and LE sprout at Stage 1, around the age of 3 weeks, whereas IR-SP sprouts only at a late stage (stage 4) of the disease (at age 3 months). The prese nt investigation shows that the presumed sprouting occurs even before the a ppearance of symptoms and prior to significant motoneuron losses. IR-5-HT c ontaining neuronal processes sprout by postnatal day 7, whereas IR-SP, -ME, -LE, and -TRH processes sprout by day 14. Hypothetically the early sprouts may contribute to the loss of motoneurons. They also respond to ciliary an d brain derives neurotrophic factors cotreatment. IR-SP neuronal processes, although they sprout by day 14, show normal fiber density by the time symp toms appear (stage 1, age 21 days). However the SP sprouting is biphasic an d a significant increase in number also occurs at an advanced stage of the disease (stage 4, age 3 months). (C) 1999 Elsevier Science Ireland Ltd. All rights reserved.