Role of endogenous pituitary adenylate cyclase activating polypeptide (PACAP) in myelination of the rodent brain: Lessons from PACAP-deficient mice

András Vincze, D. Reglodi, Z. Helyes, Hitoshi Hashimoto, Norihito Shintani, H. Ábrahám

Research output: Article

11 Citations (Scopus)

Abstract

Pituitary adenylate-cyclase activator polypeptide (PACAP), as a consequence of its effect on the elevation of intracellular cAMP level, strongly influences brain development including myelination. While proliferation of oligodendroglial progenitors is stimulated by PACAP applied in vitro, their differentiation is inhibited. However, the in vivo role of PACAP on myelination has never been examined.In the present study the role of endogenous PACAP in myelination was examined in PACAP-deficient mice, in several areas of the brain with a special attention to the cerebral cortex. In young postnatal and adult mice myelination was studied with immunohistochemistry detecting a protein present in the myelin sheath, the myelin basic protein, with Luxol Fast Blue staining and with electron microscopy. Results obtained in PACAP-deficient mice were compared to age-matched wild type controls.We found that the sequence of myelination in the PACAP-deficient animals was similar to that observed in controls. According to this, in both PACAP-deficient and wild type 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 wild type animals, and the ventrolateral part of the corpus callosum was myelinated earlier than the dorsomedial part in both groups. 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 wild type controls in all of the examined brain regions, including cerebral archi- and neocortex. The first myelinated axons in each of the examined brain regions were observed earlier in the PACAP-deficient mice than in controls. 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.We propose that 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 therefore, strengthens neuronal plasticity.

Original languageEnglish
Pages (from-to)923-935
Number of pages13
JournalInternational Journal of Developmental Neuroscience
Volume29
Issue number8
DOIs
Publication statusPublished - dec. 2011

Fingerprint

Pituitary Adenylate Cyclase-Activating Polypeptide
Rodentia
Brain
Corpus Callosum
Myelin Sheath
Neuronal Plasticity
Wild Animals
Somatosensory Cortex
Myelin Basic Protein
Neocortex
Gyrus Cinguli
Nerve Growth Factors
Motor Cortex
Adenylyl Cyclases
Cerebral Cortex
Synapses
Axons

ASJC Scopus subject areas

  • Developmental Biology
  • Developmental Neuroscience

Cite this

@article{9917d39042d04ceb8b5925c073170d1c,
title = "Role of endogenous pituitary adenylate cyclase activating polypeptide (PACAP) in myelination of the rodent brain: Lessons from PACAP-deficient mice",
abstract = "Pituitary adenylate-cyclase activator polypeptide (PACAP), as a consequence of its effect on the elevation of intracellular cAMP level, strongly influences brain development including myelination. While proliferation of oligodendroglial progenitors is stimulated by PACAP applied in vitro, their differentiation is inhibited. However, the in vivo role of PACAP on myelination has never been examined.In the present study the role of endogenous PACAP in myelination was examined in PACAP-deficient mice, in several areas of the brain with a special attention to the cerebral cortex. In young postnatal and adult mice myelination was studied with immunohistochemistry detecting a protein present in the myelin sheath, the myelin basic protein, with Luxol Fast Blue staining and with electron microscopy. Results obtained in PACAP-deficient mice were compared to age-matched wild type controls.We found that the sequence of myelination in the PACAP-deficient animals was similar to that observed in controls. According to this, in both PACAP-deficient and wild type 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 wild type animals, and the ventrolateral part of the corpus callosum was myelinated earlier than the dorsomedial part in both groups. 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 wild type controls in all of the examined brain regions, including cerebral archi- and neocortex. The first myelinated axons in each of the examined brain regions were observed earlier in the PACAP-deficient mice than in controls. 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.We propose that 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 therefore, strengthens neuronal plasticity.",
keywords = "Development, Knockout, Myelin, Oligodendroglial cells, Pituitary adenylate-cyclase activator polypeptide",
author = "Andr{\'a}s Vincze and D. Reglodi and Z. Helyes and Hitoshi Hashimoto and Norihito Shintani and H. {\'A}brah{\'a}m",
year = "2011",
month = "12",
doi = "10.1016/j.ijdevneu.2011.06.008",
language = "English",
volume = "29",
pages = "923--935",
journal = "International Journal of Developmental Neuroscience",
issn = "0736-5748",
publisher = "Elsevier Limited",
number = "8",

}

TY - JOUR

T1 - Role of endogenous pituitary adenylate cyclase activating polypeptide (PACAP) in myelination of the rodent brain

T2 - Lessons from PACAP-deficient mice

AU - Vincze, András

AU - Reglodi, D.

AU - Helyes, Z.

AU - Hashimoto, Hitoshi

AU - Shintani, Norihito

AU - Ábrahám, H.

PY - 2011/12

Y1 - 2011/12

N2 - Pituitary adenylate-cyclase activator polypeptide (PACAP), as a consequence of its effect on the elevation of intracellular cAMP level, strongly influences brain development including myelination. While proliferation of oligodendroglial progenitors is stimulated by PACAP applied in vitro, their differentiation is inhibited. However, the in vivo role of PACAP on myelination has never been examined.In the present study the role of endogenous PACAP in myelination was examined in PACAP-deficient mice, in several areas of the brain with a special attention to the cerebral cortex. In young postnatal and adult mice myelination was studied with immunohistochemistry detecting a protein present in the myelin sheath, the myelin basic protein, with Luxol Fast Blue staining and with electron microscopy. Results obtained in PACAP-deficient mice were compared to age-matched wild type controls.We found that the sequence of myelination in the PACAP-deficient animals was similar to that observed in controls. According to this, in both PACAP-deficient and wild type 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 wild type animals, and the ventrolateral part of the corpus callosum was myelinated earlier than the dorsomedial part in both groups. 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 wild type controls in all of the examined brain regions, including cerebral archi- and neocortex. The first myelinated axons in each of the examined brain regions were observed earlier in the PACAP-deficient mice than in controls. 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.We propose that 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 therefore, strengthens neuronal plasticity.

AB - Pituitary adenylate-cyclase activator polypeptide (PACAP), as a consequence of its effect on the elevation of intracellular cAMP level, strongly influences brain development including myelination. While proliferation of oligodendroglial progenitors is stimulated by PACAP applied in vitro, their differentiation is inhibited. However, the in vivo role of PACAP on myelination has never been examined.In the present study the role of endogenous PACAP in myelination was examined in PACAP-deficient mice, in several areas of the brain with a special attention to the cerebral cortex. In young postnatal and adult mice myelination was studied with immunohistochemistry detecting a protein present in the myelin sheath, the myelin basic protein, with Luxol Fast Blue staining and with electron microscopy. Results obtained in PACAP-deficient mice were compared to age-matched wild type controls.We found that the sequence of myelination in the PACAP-deficient animals was similar to that observed in controls. According to this, in both PACAP-deficient and wild type 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 wild type animals, and the ventrolateral part of the corpus callosum was myelinated earlier than the dorsomedial part in both groups. 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 wild type controls in all of the examined brain regions, including cerebral archi- and neocortex. The first myelinated axons in each of the examined brain regions were observed earlier in the PACAP-deficient mice than in controls. 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.We propose that 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 therefore, strengthens neuronal plasticity.

KW - Development

KW - Knockout

KW - Myelin

KW - Oligodendroglial cells

KW - Pituitary adenylate-cyclase activator polypeptide

UR - http://www.scopus.com/inward/record.url?scp=80455164687&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=80455164687&partnerID=8YFLogxK

U2 - 10.1016/j.ijdevneu.2011.06.008

DO - 10.1016/j.ijdevneu.2011.06.008

M3 - Article

C2 - 21726625

AN - SCOPUS:80455164687

VL - 29

SP - 923

EP - 935

JO - International Journal of Developmental Neuroscience

JF - International Journal of Developmental Neuroscience

SN - 0736-5748

IS - 8

ER -