Aims: 

Pituitary adenylate-cyclase activator polypeptide (PACAP) strongly influences brain development including myelination. While proliferation of oligodendroglial progenitors is stimulated by PACAP applied in vitro, their differentiation is inhibited. We hypothesize that endogenous PACAP exerts a similar inhibitory effect on myelination in vivo.

Methods: 

Myelination in PACAP-deficient mice was studied in several areas of the brain using immunohistochemistry detecting myelin basic protein (MBP), and the results obtained were compared to age-matched wild type (WT) controls.

Results: 

The sequence of myelination in the PACAP-deficient animals was similar to that observed in WT. According to this, in both PACAP-deficient and WT mice, the somatosensory cortex was myelinated before motor areas that preceded the myelination of associational cortical areas. Archicortical associational areas such as the cingulate cortex were myelinated before neocortical areas. Myelination in the corpus callosum followed the known rostro-caudal direction in both PACAP-deficient and WT animals. In contrast to the similarity in its sequence, striking difference was found in the onset of myelination that started earlier in PACAP-deficient mice than in WT in all of the examined brain regions. The first myelinated axons were observed earlier in the PACAP-deficient mice than in WT. When age-matched animals of the two groups were compared, density of myelinated fibers in the PACAP-deficient mice was higher than in controls in all of the examined areas.

Conclusion: 

Endogenous PACAP exerts an inhibitory role on myelination in vivo. Since myelin sheath of the central nervous system contains several factors blocking neurite outgrowth, inhibition of myelination by PACAP gives time for axonal development and synapse formation, and strengthens neuronal plasticity.

Support: 

OTKA K72592, CNK78480, T73044; ETT 278/2009; Bolyai Scholarship