Journal of Molecular Neuroscience

, Volume 61, Issue 4, pp 468–478 | Cite as

Early Neurobehavioral Development of Mice Lacking Endogenous PACAP

  • Jozsef Farkas
  • Balazs Sandor
  • Andrea Tamas
  • Peter Kiss
  • Hitoshi Hashimoto
  • Andras D. Nagy
  • Balazs D. Fulop
  • Tamas Juhasz
  • Sridharan Manavalan
  • Dora ReglodiEmail author


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.


Neurodevelopment Reflex Knockout Neuropeptide Trophic factor 



OTKA K104984, PD109644, National Research, Development and Innovation Fund K119759, GINOP-2.3.2-15-2016-00050 “PEPSYS”, PTE AOK Research Grant, Hungarian Brain Research Program—KTIA_13_NAP-A-III/5, Centre for Neuroscience of the University of Pecs. The UNKP-16-4-IV New National Excellence Program of the Ministry of Human Capacities, and Centre for Neuroscience, University of Pecs, TAMOP 4.2.4.A/2-11-1-2012-0001 “National Excellence Program. Bolyai János Scholarship , Szodoray Lajos and Magyary Zoltán Funds by the European Union and the State of Hungary, University of Debrecen (RH/751/2015). The present scientific contribution is dedicated to the 650th anniversary of the foundation of the University of Pecs, Hungary.

Compliance with Ethical Standards

Ethics Statement

The study was carried out in accordance with ethical guidelines of the University of Pecs, Hungary (BA02/2000-15024/2011).


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Copyright information

© Springer Science+Business Media New York 2017

Authors and Affiliations

  • Jozsef Farkas
    • 1
  • Balazs Sandor
    • 1
    • 2
  • Andrea Tamas
    • 1
  • Peter Kiss
    • 1
  • Hitoshi Hashimoto
    • 3
  • Andras D. Nagy
    • 1
  • Balazs D. Fulop
    • 1
  • Tamas Juhasz
    • 4
  • Sridharan Manavalan
    • 1
    • 5
  • Dora Reglodi
    • 1
    Email author
  1. 1.Department of Anatomy, Medical SchoolUniversity of PecsPecsHungary
  2. 2.Department of Dentistry, Oral and Maxillofacial SurgeryUniversity of PecsPecsHungary
  3. 3.Laboratory of Molecular Neuropharmacology, Graduate School of Pharmaceutical Sciences and Molecular Research Center for Children’s Mental Development, United Graduate School of Child DevelopmentOsaka UniversityOsakaJapan
  4. 4.Department of Anatomy, Histology and EmbryologyUniversity of DebrecenDebrecenHungary
  5. 5.Department of Basic SciencesNational University of Health SciencesFloridaUSA

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