Cited by 99Neuroscience of respiration and sleepGenetic Syndromes and ImprintingGenetics and Neurodevelopmental Disorders

Developmental Abnormalities of Neuronal Structure and Function in Prenatal Mice Lacking the Prader-Willi Syndrome Gene Necdin

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Pagliardini, Silvia, Ren, Jun, Wevrick, Rachel, Greer, John J.·2005·The American Journal of Pathology

Abstract

Necdin (Ndn) is one of a cluster of genes deleted in the neurodevelopmental disorder Prader-Willi syndrome (PWS). Ndntm2Stw mutant mice die shortly after birth because of abnormal respiratory rhythmogenesis generated by a key medullary nucleus, the pre-Bötzinger complex (preBötC). Here, we address two fundamental issues relevant to its pathogenesis. First, we performed a detailed anatomical study of the developing medulla to determine whether there were defects within the preBötC or synaptic inputs that regulate respiratory rhythmogenesis. Second, in vitro studies determined if the unstable respiratory rhythm in Ndntm2Stw mice could be normalized by neuromodulators. Anatomical defects in Ndntm2Stw mice included defasciculation and irregular projections of axonal tracts, aberrant neuronal migration, and a major defect in the cytoarchitecture of the cuneate/gracile nuclei, including dystrophic axons. Exogenous application of neuromodulators alleviated the long periods of slow respiratory rhythms and apnea, but some instability of rhythmogenesis persisted. We conclude that deficiencies in the neuromodulatory drive necessary for preBötC function contribute to respiratory dysfunction of Ndntm2Stw mice. These abnormalities are part of a more widespread deficit in neuronal migration and the extension, arborization, and fasciculation of axons during early stages of central nervous system development that may account for respiratory, sensory, motor, and behavioral problems associated with PWS.

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  • Necdin-deficient mice have small brainstem nuclei and disorganized axonal tracts in the medulla.

    “Necdin-deficient mice have small brainstem nuclei and disorganized axonal tracts in the medulla [271].”

    From Autism spectrum disorder: neuropathology and animal models (2017) · cites this paper as [271]

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1 of the 92 references couldn’t be matched to a known paper.

Research works printed but not linked: 3

  1. Feldman JL, Mitchell GS, Nattie EE: Breathing: rhythmicity, plasticity, chemosensitivity. Ann Rev Neurosci 2003, 26:239 -266
  2. Kozlov SV, Gerard M, Stewart CL: Morphological analysis of the respiratory pathway in perinatal mice deficient for necdin: a compo- nent of the pathology of Prade-Willi syndrome. Soc Neurosci Abs 2001, 694:10
  3. Swaab DF: Prader-Willi syndrome and the hypothalamus. Acta Pae- diatr 1997, 423:50 -54

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Authors
Pagliardini, S., Ren, J., Wevrick, R., & Greer, J. J.
Affiliations
University of Alberta (CA)
Corresponding author
Greer, John J.
Venue
The American Journal of Pathology
Publisher
Elsevier BV
Published
2005-07
Volume
167
Issue
1
Pages
175-191
ISSN
0002-9440 (ISSN-L)
OpenAlex
W2024673645
Cited by
99
References
92
Citations by year
2026: 1 · 2025: 1 · 2024: 2 · 2023: 2 · 2022: 2 · 2021: 5 · 2020: 3 · 2019: 6 · 2018: 2 · 2017: 4 · 2016: 6 · 2014: 5 · 2013: 5 · 2012: 10
FWCI
3.31
Type
journal article
Language
en
Open access
Locations
  • American Journal Of Pathology (publishedVersion)
  • PubMed Central (publishedVersion)
  • PubMed (publishedVersion)
Funders
  • Fondation pour la Recherche Médicale
  • Canadian Institutes of Health Research
Topics
  • Life Sciences › Neuroscience › Endocrine and Autonomic Systems › Neuroscience of respiration and sleep
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Genetics › Genetic Syndromes and Imprinting
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Genetics › Genetics and Neurodevelopmental Disorders
Keywords
Prader-Willi syndrome, NDN, pre-Bötzinger complex, respiratory rhythmogenesis, medulla oblongata, neuronal migration, axonal fasciculation, cuneate nucleus, gracile nucleus, neuromodulators, apnea, developmental abnormalities
MeSH terms
Animals, Diaphragm, Disease Models, Animal, Female, Fetus, Immunohistochemistry, Mice, Neurologic Mutants, Nerve Tissue Proteins, Neurons, Nuclear Proteins, Organ Culture Techniques, Prader-Willi Syndrome, Pregnancy, Respiratory Center, Spinal Cord, Microscopy, Confocal, Mice

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