Early Neurobehavioral Development of Mice Lacking Endogenous PACAP.
Pituitary adenylate cyclase activating polypeptide (PACAP) is a multifunctional neuropeptide. In addition to its diverse physiological roles, PACAP has important functions in the embryonic development of various tissues, and it is also considered as a trophic factor during development and in the case of neuronal injuries. Data suggest that the development of the nervous system is severely affected by the lack of endogenous PACAP. Short-term neurofunctional outcome correlates with long-term functional deficits; however, the early neurobehavioral development of PACAP-deficient mice has not yet been evaluated. Therefore, the aim of the present study was to describe the postnatal development of physical signs and neurological reflexes in mice partially or completely lacking PACAP. We examined developmental hallmarks during the first 3 weeks of the postnatal period, during which period most neurological reflexes and motor coordination show most intensive development, and we describe the neurobehavioral development using a complex battery of tests. In the present study, we found that PACAP-deficient mice had slower weight gain throughout the observation period. Interestingly, mice partially lacking PACAP weighed significantly less than homozygous mice. There was no difference between male and female mice during the first 3 weeks. Some other signs were also more severely affected in the heterozygous mice than in the homozygous mice, such as air righting, grasp, and gait initiation reflexes. Interestingly, incisor teeth erupted earlier in mice lacking PACAP. Motor coordination, shown by the number of foot-faults on an elevated grid, was also less developed in PACAP-deficient mice. In summary, our results show that mice lacking endogenous PACAP have slower weight gain during the first weeks of development and slower neurobehavioral development regarding a few developmental hallmarks.
Department of Anatomy, Medical School, University of Pecs, Szigeti u 12, 7624, Pecs, Hungary.
Jozsef
J
Farkas
Department of Anatomy, Medical School, University of Pecs, Szigeti u 12, 7624, Pecs, Hungary.|Department of Dentistry, Oral and Maxillofacial Surgery, University of Pecs, Pecs, Hungary.
Balazs
B
Sandor
Department of Anatomy, Medical School, University of Pecs, Szigeti u 12, 7624, Pecs, Hungary.
Andrea
A
Tamas
Department of Anatomy, Medical School, University of Pecs, Szigeti u 12, 7624, Pecs, Hungary.
Peter
P
Kiss
Laboratory of Molecular Neuropharmacology, Graduate School of Pharmaceutical Sciences and Molecular Research Center for Children's Mental Development, United Graduate School of Child Development, Osaka University, Osaka, Japan.
Hitoshi
H
Hashimoto
Department of Anatomy, Medical School, University of Pecs, Szigeti u 12, 7624, Pecs, Hungary.
Andras D
AD
Nagy
Department of Anatomy, Medical School, University of Pecs, Szigeti u 12, 7624, Pecs, Hungary.
Balazs D
BD
Fulop
Department of Anatomy, Histology and Embryology, University of Debrecen, Debrecen, Hungary.
Tamas
T
Juhasz
Department of Anatomy, Medical School, University of Pecs, Szigeti u 12, 7624, Pecs, Hungary.|Department of Basic Sciences, National University of Health Sciences, Florida, USA.
Sridharan
S
Manavalan
Department of Anatomy, Medical School, University of Pecs, Szigeti u 12, 7624, Pecs, Hungary. dora.reglodi@aok.pte.hu.
Dora
D
Reglodi
D000818:Animals; D001835:Body Weight; D005260:Female; D006579:Heterozygote; D006720:Homozygote; D007180:Incisor / Q000254:growth & development / Q000378:metabolism / Q000648:ultrastructure; D008297:Male; D051379:Mice; D009043:Motor Activity; D009420:Nervous System / Q000254:growth & development* / Q000378:metabolism; D051219:Pituitary Adenylate Cyclase-Activating Polypeptide / Q000172:deficiency / Q000235:genetics*; D012018:Reflex
C495402:Adcyap1 protein, mouse; D051219:Pituitary Adenylate Cyclase-Activating Polypeptide
Knockout; Neurodevelopment; Neuropeptide; Reflex; Trophic factor