Sensory nociceptive axons invade the cerebellum of transgenic mice overexpressing nerve growth factor

Transgenic mice possessing elevated levels of mRNA expression and synthesis for the neurotrophin nerve growth factor among astrocytes display a robust ingrowth of new sympathetic fibers to the cerebellum. In this investigation, we report that the cerebellum of these mice also possesses a dense plexus of aberrant axons of sensory origin. Axons stained immunohistochemically for calcitonin gene-related peptide were seen in the transgenic cerebellum as early as one week after birth. The density of these axons dramatically increased with age. Immunopositive axons were confined predominantly to the deep white matter of the cerebellum in the adult transgenic mice, with a smaller number of axons seen coursing along blood vessels in the gray matter. Axons stained immunohistochemically for the neurotrophin receptor, p75NTR, displayed a similar pattern of distribution and density as those immunostained for calcitonin gene-related peptide. Wild-type post-natal and adult animals lacked such calcitonin gene-related peptide- and p75NTR-immunoreactive 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). This investigation demonstrates that overexpression of nerve growth factor is capable of inducing the directional growth of collateral axons of sensory neurons into the undamaged mammalian central nervous system.