Effects of Purkinje cell degeneration on the noradrenergic projection to mouse cerebellar cortex.
We have examined the effects of a genetically programmed target cell death on the noradrenergic afferent projection to mouse cerebellar cortex. We have observed that the noradrenergic axon terminals originating in in locus coeruleus are maintained in the cerebellar cortex of the Purkinje cell degeneration (pcd) mutant mouse in spite of the absence of Purkinje cells, the targets for the noradrenergic projection. The number of noradrenergic terminals in the atrophic mutant cerebellar cortex is approximately normal as assessed by counts of fibers exhibiting catecholamine fluorescence and by measurement of high affinity uptake of tritium-labeled norepinephrine (NE) by synaptosomes prepared from cerebellar cortex. An increased density of NE fibers is observed which appears to be a consequence of reduced cerebellar mass in the mutant. Although the number of noradrenergic terminals is unaffected, morphological and biochemical alterations are observed in this system. The fibers are more brightly fluorescent in mutant than in normal mice and their pattern is less orderly. The content of the endogenous transmitter, NE, is increased from 150 to 170% whereas the activity of the rate-limiting enzyme tyrosine hydroxylase (TH) is reduced to about 60% of normal values. These changes appear to be permanent as they are still present in 6 month-old mutant animals, the oldest studied. No alterations in either NE content or TH activity are found in pcd/pcd hippocampus, another target for the locus coeruleus axons.
D000344:Afferent Pathways / Q000033:anatomy & histology; D000818:Animals; D001369:Axons / Q000648:ultrastructure; D002470:Cell Survival; D002525:Cerebellar Cortex / Q000033:anatomy & histology*; D005455:Fluorescent Antibody Technique; D006624:Hippocampus / Q000033:anatomy & histology; D008125:Locus Coeruleus / Q000033:anatomy & histology*; D051379:Mice; D008807:Mice, Inbred BALB C; D008810:Mice, Inbred C57BL; D008818:Mice, Neurologic Mutants; D009410:Nerve Degeneration; D009412:Nerve Fibers / Q000648:ultrastructure; D009638:Norepinephrine / Q000378:metabolism*; D011689:Purkinje Cells / Q000648:ultrastructure*; D013574:Synaptosomes / Q000648:ultrastructure; D014446:Tyrosine 3-Monooxygenase / Q000378:metabolism
D014446:Tyrosine 3-Monooxygenase; D009638:Norepinephrine