SENSORY NOCICEPTIVE AXONS INVADE THE CEREBELLUM OF TRANSGENIC MICE OVEREXPRESSING NERVE GROWTH-FACTOR

Transgenic mice possessing elevated levels of mRNA expression and synt hesis for the neurotrophin nerve growth factor among astrocytes displa y a robust ingrowth of new sympathetic fibers to the cerebellum. In th is investigation, we report that the cerebellum of these mice also pos sesses a dense plexus of aberrant axons of sensory origin, Axons stain ed immunohistochemically for calcitonin gene-related peptide were seen in the transgenic cerebellum as early as one week after birth. The de nsity of these axons dramatically increased with age. Immunopositive a xons were confined predominantly to the deep white matter of the cereb ellum in the adult transgenic mice, with a smaller number of axons see n coursing along blood vessels in the gray matter. Axons stained immun ohistochemically for the neurotrophin receptor, p75(NTR), displayed a similar pattern of distribution and density as those immunostained for calcitonin gene-related peptide. Wild-type post-natal and adult anima ls lacked such calcitonin gene-related peptide-and p75(NTR)-immunoreac tive axons in the cerebellum. Retrograde labelling revealed that these axons within the transgenic cerebellum originated from neurons in the sensory trigeminal and dorsal root ganglia (upper cervical levels). T his investigation demonstrates that overexpression of nerve growth fac tor is capable of inducing the directional growth of collateral axons of sensory neurons into the undamaged mammalian central nervous system . (C) 1997 Elsevier Science B.V.