Chaisuksunt, Vipavadee; (1999) Differential expression of regeneration relevant molecules in neurons of adult rat brain after injury and the implantation of peripheral nerve grafts. Doctoral thesis (Ph.D), UCL (University College London).

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Abstract

This study was concerned with the pattern of expression of several regeneration relevant molecules in the striatum, thalamus and cerebellum of adult rats and correlating this with differences in the regenerative potential of the neurons. The molecules investigated were neurotrophin receptors (Trk A and p75), the growth associated protein GAP-43, the immediate early gene c-jun and, in particular, the cell recognition molecules L1 and close homologue of L1 (CHL1). Segments of peripheral nerve were autografted into the striatum, thalamus or cerebellum and expression of these molecules was investigated by non-radioactive in situ hybridization with cRNA probes to detect mRNAs, and by immunocytochemistry to detect the proteins. In some cases these techniques were combined with retrograde labelling from the distal end of the graft to identify regenerating neurons. In all 3 sites CHL1 mRNA was upregulated in neurons which regenerated axons into the grafts. In the striatum, the neurons which displayed CHL1 mRNA upregulation included aspiny cholinergic interneurons and these neurons also upregulated c-jun mRNA, trk A as well as p75 expression. After graft implantation into the thalamus, CHL1 mRNA was upregulated almost exclusively in neurons of the thalamic reticular nucleus which were also identified as regenerating neurons by retrograde labelling. In the cerebellum, CHL1 mRNA was upregulated by regenerating neurons of the deep cerebellar nuclei, some of which also expressed LI, c-jun, and GAP-43 mRNAs, but not by non-regenerating neurons of the cerebellar cortex. However, some of Purkinje cells close to the graft expressed c-jun mRNA. These findings suggest that regenerating CNS neurons increase their expression of a group of molecules, including CHL1, which may play an important role in the regrowth of their axons.

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