| Description |
The study of neurogenesis is important for understanding the causes of many developmental defects, and crucial for the prevention and treatment of neuronal degeneration and injury. The olfactory system is an excellent model for the study of neurogenesis due to its unique ability to continuously regenerate olfactory sensory neurons (OSNs), even in adults. Pituitary adenylate cyclaseactivating polypeptide (PACAP) functions in many aspects of neurogenesis and is present in the olfactory epithelium (OE). We examined the role of PACAP, in vivo, in the development and regeneration of the OE by comparing PACAP knock-out (KO) and wild-type (WT) mice. In early postnatal development, proliferation levels are reduced in PACAP KO mice but the number of OSNs is not different from WT mice. By 1 week of age, no differences between PACAP KO and WT mice were observed. Given that other growth factors may be present during development and could compensate for the absence of PACAP, we also examined adult OE. Although adult PACAP KO mice have normal food odorant detection, the OE exhibits decreased epithelial thickness due to loss of cells. However, immunostaining revealed no differences in OSN numbers between PACAP KO and WT mice, although expression levels for markers of OSNs were increased. Surprisingly, PACAP KO mice show increased proliferation compared to WT mice. Injury-induced degradation, resulting in iv regeneration of the OE, was also examined in adult PACAP KO and WT mice. Immediately after chemical insult, PACAP KO mice exhibited more inflammation than WT mice. A faster decline in OSNs, leading to quicker onset of anosmia, was seen in PACAP KO mice. In addition, PACAP KO mice recovered from anosmia more quickly, likely due to increased proliferation levels before insult. However, 1 week following insult there were no differences between PACAP KO and WT mice, and both groups were recovered functionally after 2 weeks. We conclude that PACAP has a minor influence promoting proliferation during OE development. PACAP is not required for adult proliferation, but is required for the survival and maintenance of adult OE. This study suggests PACAP may be important for future therapies aimed at promoting neuronal survival. |
