Zebrafish models of human motor neuron diseases: Advantages and limitations

Patrick J. Babin, Cyril Goizet, Demetrio Raldúa
Progress in Neurobiology. 2014-07-01; 118: 36-58
DOI: 10.1016/J.PNEUROBIO.2014.03.001

Lire sur PubMed

1. Prog Neurobiol. 2014 Jul;118:36-58. doi: 10.1016/j.pneurobio.2014.03.001. Epub
2014 Apr 3.

Zebrafish models of human motor neuron diseases: advantages and limitations.

Babin PJ(1), Goizet C(2), Raldúa D(3).

Author information:
(1)Univ. Bordeaux, Maladies Rares: Génétique et Métabolisme (MRGM), EA 4576,
Talence, France. Electronic address: .
(2)Univ. Bordeaux, Maladies Rares: Génétique et Métabolisme (MRGM), EA 4576,
Talence, France; CHU Bordeaux, Hôpital Pellegrin, Service de Génétique Médicale,
Bordeaux, France.
(3)IDÆA-CSIC, Barcelona, Spain. Electronic address: .

Motor neuron diseases (MNDs) are an etiologically heterogeneous group of
disorders of neurodegenerative origin, which result in degeneration of lower
(LMNs) and/or upper motor neurons (UMNs). Neurodegenerative MNDs include pure
hereditary spastic paraplegia (HSP), which involves specific degeneration of
UMNs, leading to progressive spasticity of the lower limbs. In contrast, spinal
muscular atrophy (SMA) involves the specific degeneration of LMNs, with
symmetrical muscle weakness and atrophy. Amyotrophic lateral sclerosis (ALS), the
most common adult-onset MND, is characterized by the degeneration of both UMNs
and LMNs, leading to progressive muscle weakness, atrophy, and spasticity. A
review of the comparative neuroanatomy of the human and zebrafish motor systems
showed that, while the zebrafish was a homologous model for LMN disorders, such
as SMA, it was only partially relevant in the case of UMN disorders, due to the
absence of corticospinal and rubrospinal tracts in its central nervous system.
Even considering the limitation of this model to fully reproduce the human UMN
disorders, zebrafish offer an excellent alternative vertebrate model for the
molecular and genetic dissection of MND mechanisms. Its advantages include the
conservation of genome and physiological processes and applicable in vivo tools,
including easy imaging, loss or gain of function methods, behavioral tests to
examine changes in motor activity, and the ease of simultaneous chemical/drug
testing on large numbers of animals. This facilitates the assessment of the
environmental origin of MNDs, alone or in combination with genetic traits and
putative modifier genes. Positive hits obtained by phenotype-based small-molecule
screening using zebrafish may potentially be effective drugs for treatment of
human MNDs.

Copyright © 2014 The Authors. Published by Elsevier Ltd.. All rights reserved.

DOI: 10.1016/j.pneurobio.2014.03.001
PMID: 24705136 [Indexed for MEDLINE]

Auteurs Bordeaux Neurocampus