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 motoneuron diseases. Besides showing the loss of motoneurons when the symptoms are expressed around the age of 3 weeks, we have also demonstrated the presumed ‘sprouting' of neuronal processes in the cervical spinal ventral horn which contain immunoreactive (IR) serotonin (5-HT), substance P (SP) and methionine and leucine enkephalins (ME, LE), as well as thyrotropin-releasing 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 present investigation shows that the presumed sprouting occurs even before the appearance of symptoms and prior to significant motoneuron losses. IR-5-HT containing 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 and brain derives neurotrophic factors cotreatment. IR-SP neuronal processes, although they sprout by day 14, show normal fiber density by the time symptoms appear (stage 1, age 21 days). However the SP sprouting is biphasic and a significant increase in number also occurs at an advanced stage of the disease (stage 4, age 3 months).