PMID- 8027772 OWN - NLM STAT- MEDLINE DCOM- 19940811 LR - 20191101 IS - 0270-6474 (Print) IS - 1529-2401 (Electronic) IS - 0270-6474 (Linking) VI - 14 IP - 7 DP - 1994 Jul TI - Transforming growth factor alpha (TGF alpha) expression in degenerating motoneurons of the murine mutant wobbler: a neuronal signal for astrogliosis? PG - 4206-16 AB - The enhanced expression of the trophic factor transforming growth factor alpha (TGF alpha) in reactive astrocytes following CNS injury suggests that TGF alpha has a role in the development of astrogliosis. We explored this hypothesis in the murine mutant wobbler, which presents a progressive motoneuronal degeneration associated with an astrogliosis. Evolution of astrogliosis, and expression of TGF alpha precursor (pro-TGF alpha) and of its receptor were examined over the course of the disease, using genetically diagnosed animals and immunocytochemical techniques. We report here that degenerating motoneurons of the cervical spinal cord and a subset of astrocytes express pro-TGF alpha, prior to the onset of astrogliosis, when the first clinical manifestations of the disease are observed at 4 weeks of age. TGF alpha expression appeared strongly correlated with motoneuronal degeneration. All pro-TGF alpha-immunoreactive neurons exhibited a degenerative morphology, and the number of pro-TGF alpha-immunoreactive neurons increased with the progression of the disease. At the glial level, we observed that astrogliosis was a transitory phenomenon in the wobbler mice, developing in coordination with the motoneuronal expression of pro-TGF alpha. Astrogliosis became evident in 6-week-old wobbler mice, when the number of pro-TGF alpha-immunoreactive motoneurons was maximal, and regressed in older mutant mice in correlation with the disappearance of pro-TGF alpha-immunoreactive motoneurons. Furthermore, TGF alpha/EGF receptor immunoreactivity was exclusively localized in a subset of reactive astrocytes, its expression following closely the course of the astrogliosis. These data show that TGF alpha synthesis by the affected motoneurons is an early event in the course of the wobbler disease, and suggest a role for TGF alpha as a neuronal inducer of astrocytic reactivity. FAU - Junier, M P AU - Junier MP AD - CJF INSERM 91-02, Fac Medecine, Creteil, France. FAU - Coulpier, M AU - Coulpier M FAU - Le Forestier, N AU - Le Forestier N FAU - Cadusseau, J AU - Cadusseau J FAU - Suzuki, F AU - Suzuki F FAU - Peschanski, M AU - Peschanski M FAU - Dreyfus, P A AU - Dreyfus PA LA - eng PT - Journal Article PT - Research Support, Non-U.S. Gov't PL - United States TA - J Neurosci JT - The Journal of neuroscience : the official journal of the Society for Neuroscience JID - 8102140 RN - 0 (Molecular Probes) RN - 0 (Transforming Growth Factor alpha) RN - EC 2.7.10.1 (ErbB Receptors) SB - IM MH - Animals MH - Astrocytes/*metabolism MH - Base Sequence MH - ErbB Receptors/metabolism MH - Gliosis/*metabolism MH - Mice MH - Mice, Neurologic Mutants MH - Molecular Probes/genetics MH - Molecular Sequence Data MH - Motor Neurons/*metabolism MH - Neck MH - *Nerve Degeneration MH - Polymerase Chain Reaction MH - Spinal Cord/metabolism MH - Time Factors MH - Transforming Growth Factor alpha/*metabolism PMC - PMC6577032 EDAT- 1994/07/01 00:00 MHDA- 1994/07/01 00:01 PMCR- 1995/01/01 CRDT- 1994/07/01 00:00 PHST- 1994/07/01 00:00 [pubmed] PHST- 1994/07/01 00:01 [medline] PHST- 1994/07/01 00:00 [entrez] PHST- 1995/01/01 00:00 [pmc-release] AID - 10.1523/JNEUROSCI.14-07-04206.1994 [doi] PST - ppublish SO - J Neurosci. 1994 Jul;14(7):4206-16. doi: 10.1523/JNEUROSCI.14-07-04206.1994.