Neonatal transection of the infraorbital nerve increases the expression of proteins related to neuronal death in the principal sensory nucleus of the trigeminal nerve

Neonatal lesion of the primary afferents in the infraorbital nerve causes the death of one-third of the neurons in the second-order target, the principal sensory nucleus of the trigeminal nerve (PSN). We examined the expression of two candidate 'death' proteins, p53 and the antigen recognized by the antibody ALZ-50, in the normal and deafferented PSN. In addition, the effect of neonatal transection of the infraorbital nerve (a major component of the trigeminal nerve) on protein expression was examined. The expression of c-fos in the developing PSN was also studied as an index of metabolic activity. Protein expression was measured using quantitative analyses of immunoblots and immunohistochemical preparations. The expression of p53- and ALZ-50-immunoreactivity in the normal PSN peaked during the first postnatal week. Transection of the infraorbital nerve directly affected the expression of p53 and the ALZ50-positive antigen. The immunoblots showed that whereas p53 amounts were unaffected by the lesion, ALZ-50 expression was significantly upregulated in the ipsilateral PSN 2 h and 2 days postlesion. The density of p53- and ALZ-50-immunoreactive neurons was significantly higher in the ventral ipsilateral PSN (i.e., the target of the transected infraorbital nerve) than in the contralateral PSN. c-fos expression selectively and transiently rose in the ventral ipsilateral PSN within 2 h of the lesion. Thus, both p53 and the ALZ-50-positive antigen are involved in neuronal death. In light of data suggesting that ALZ-50 recognizes a phosphorylated form of p53, we conclude that neuronal death in the developing nervous system involves the post-translational modification of an existing protein, p53. The increase in ALZ-50 expression apparently occurs during a catabolic phase of neuronal death, as indicated by the increase in c-fos expression. (C) 1997 Elsevier Science B.V.