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Hereditary lissencephaly and cerebellar hypoplasia in Churra lambs.

Pérez V, Suárez-Vega A, Fuertes M, Benavides J, Delgado L, Ferreras MC, Arranz JJ - BMC Vet. Res. (2013)

Bottom Line: Lissencephaly is a rare developmental brain disorder in veterinary and human medicine associated with defects in neuronal migration leading to a characteristic marked reduction or absence of the convolutional pattern of the cerebral hemispheres.The hippocampus was also markedly disorganised and the number and size of lobules were reduced in the cerebellum.Histopathological features observed in the cerebral cortex and hippocampus are consistent with a possible failure in neuronal migration during brain development.

View Article: PubMed Central - HTML - PubMed

Affiliation: Departamento de Sanidad Animal (Anatomía Patológica), Instituto de Ganadería de Montaña (CSIC-ULE), Facultad de Veterinaria, Universidad de León, Campus de Vegazana s/n, León 24071, Spain. vperp@unileon.es

ABSTRACT

Background: Lissencephaly is a rare developmental brain disorder in veterinary and human medicine associated with defects in neuronal migration leading to a characteristic marked reduction or absence of the convolutional pattern of the cerebral hemispheres. In many human cases the disease has a genetic basis. In sheep, brain malformations, mainly cerebellar hypoplasia and forms of hydrocephalus, are frequently due to in utero viral infections. Although breed-related malformations of the brain have been described in sheep, breed-related lissencephaly has not been previously recorded in a peer reviewed publication.

Results: Here we report neuropathological findings in 42 newborn lambs from a pure Churra breed flock, with clinical signs of weakness, inability to walk, difficulty in sucking and muscular rigidity observed immediately after birth. All the lambs showed near-total agyria with only a rudimentary formation of few sulci and gyri, and a severe cerebellar hypoplasia. On coronal section, the cerebral grey matter was markedly thicker than that of age-matched unaffected lambs and the ventricular system was moderately dilated. Histologically, the normal layers of the cerebral cortex were disorganized and, using an immunohistochemical technique against neurofilaments, three layers were identified instead of the six present in normal brains. The hippocampus was also markedly disorganised and the number and size of lobules were reduced in the cerebellum. Heterotopic neurons were present in different areas of the white matter. The remainder of the brain structures appeared normal. The pathological features reported are consistent with the type LCH-b (lissencephaly with cerebellar hypoplasia group b) defined in human medicine. No involvement of pestivirus or bluetongue virus was detected by immunohistochemistry. An analysis of pedigree data was consistent with a monogenic autosomal recessive pattern inheritance.

Conclusions: The study describes the clinical and pathological findings of lissencephaly with cerebellar hypoplasia in Churra lambs for which an autosomal recessive inheritance was the most likely cause. Histopathological features observed in the cerebral cortex and hippocampus are consistent with a possible failure in neuronal migration during brain development. This report suggests that lissencephaly should be considered in the differential diagnosis of congenital neurological disease in newborn lambs showing weakness, inability to walk and difficulty sucking.

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Immunohistochemistry for neurofilaments. Sections of the cerebral cortex from a control (a) and a lissencephalic (b) brain, taken at the same magnification and immunolabelled for neurofilaments. In the control brain, the typical layering of this area (I to VI) can be seen, where the neurons from the pyramidal layers show the strongest signal. In the lissencephalic brain, three different layers can be identified according to neurofilament expression. Immunoperoxidase staining for neurofilaments.
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Figure 4: Immunohistochemistry for neurofilaments. Sections of the cerebral cortex from a control (a) and a lissencephalic (b) brain, taken at the same magnification and immunolabelled for neurofilaments. In the control brain, the typical layering of this area (I to VI) can be seen, where the neurons from the pyramidal layers show the strongest signal. In the lissencephalic brain, three different layers can be identified according to neurofilament expression. Immunoperoxidase staining for neurofilaments.

Mentions: In the control brain sections immunolabelled with antibodies against NF-L neurofilaments, the six conventional layers were identified in the cerebral cortex, and the two pyramidal neurone layers (III and V) had the strongest intensity of immunostaining (Figure 4a). In contrast, in the sections from the affected brains, only three layers were discernible (Figure 4b). Besides the outer marginal zone, corresponding to the molecular layer, that did not show immunolabelling, a thick layer formed mainly by pyramidal neurons of different sizes, some of them showing intense neurofilament expression, was present (Figure 4b). Finally, an internal layer not discernible in HE sections, adjacent to the white matter, with a more reduced immunostaining, was identified (Figure 4b).


Hereditary lissencephaly and cerebellar hypoplasia in Churra lambs.

Pérez V, Suárez-Vega A, Fuertes M, Benavides J, Delgado L, Ferreras MC, Arranz JJ - BMC Vet. Res. (2013)

Immunohistochemistry for neurofilaments. Sections of the cerebral cortex from a control (a) and a lissencephalic (b) brain, taken at the same magnification and immunolabelled for neurofilaments. In the control brain, the typical layering of this area (I to VI) can be seen, where the neurons from the pyramidal layers show the strongest signal. In the lissencephalic brain, three different layers can be identified according to neurofilament expression. Immunoperoxidase staining for neurofilaments.
© Copyright Policy - open-access
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC3750509&req=5

Figure 4: Immunohistochemistry for neurofilaments. Sections of the cerebral cortex from a control (a) and a lissencephalic (b) brain, taken at the same magnification and immunolabelled for neurofilaments. In the control brain, the typical layering of this area (I to VI) can be seen, where the neurons from the pyramidal layers show the strongest signal. In the lissencephalic brain, three different layers can be identified according to neurofilament expression. Immunoperoxidase staining for neurofilaments.
Mentions: In the control brain sections immunolabelled with antibodies against NF-L neurofilaments, the six conventional layers were identified in the cerebral cortex, and the two pyramidal neurone layers (III and V) had the strongest intensity of immunostaining (Figure 4a). In contrast, in the sections from the affected brains, only three layers were discernible (Figure 4b). Besides the outer marginal zone, corresponding to the molecular layer, that did not show immunolabelling, a thick layer formed mainly by pyramidal neurons of different sizes, some of them showing intense neurofilament expression, was present (Figure 4b). Finally, an internal layer not discernible in HE sections, adjacent to the white matter, with a more reduced immunostaining, was identified (Figure 4b).

Bottom Line: Lissencephaly is a rare developmental brain disorder in veterinary and human medicine associated with defects in neuronal migration leading to a characteristic marked reduction or absence of the convolutional pattern of the cerebral hemispheres.The hippocampus was also markedly disorganised and the number and size of lobules were reduced in the cerebellum.Histopathological features observed in the cerebral cortex and hippocampus are consistent with a possible failure in neuronal migration during brain development.

View Article: PubMed Central - HTML - PubMed

Affiliation: Departamento de Sanidad Animal (Anatomía Patológica), Instituto de Ganadería de Montaña (CSIC-ULE), Facultad de Veterinaria, Universidad de León, Campus de Vegazana s/n, León 24071, Spain. vperp@unileon.es

ABSTRACT

Background: Lissencephaly is a rare developmental brain disorder in veterinary and human medicine associated with defects in neuronal migration leading to a characteristic marked reduction or absence of the convolutional pattern of the cerebral hemispheres. In many human cases the disease has a genetic basis. In sheep, brain malformations, mainly cerebellar hypoplasia and forms of hydrocephalus, are frequently due to in utero viral infections. Although breed-related malformations of the brain have been described in sheep, breed-related lissencephaly has not been previously recorded in a peer reviewed publication.

Results: Here we report neuropathological findings in 42 newborn lambs from a pure Churra breed flock, with clinical signs of weakness, inability to walk, difficulty in sucking and muscular rigidity observed immediately after birth. All the lambs showed near-total agyria with only a rudimentary formation of few sulci and gyri, and a severe cerebellar hypoplasia. On coronal section, the cerebral grey matter was markedly thicker than that of age-matched unaffected lambs and the ventricular system was moderately dilated. Histologically, the normal layers of the cerebral cortex were disorganized and, using an immunohistochemical technique against neurofilaments, three layers were identified instead of the six present in normal brains. The hippocampus was also markedly disorganised and the number and size of lobules were reduced in the cerebellum. Heterotopic neurons were present in different areas of the white matter. The remainder of the brain structures appeared normal. The pathological features reported are consistent with the type LCH-b (lissencephaly with cerebellar hypoplasia group b) defined in human medicine. No involvement of pestivirus or bluetongue virus was detected by immunohistochemistry. An analysis of pedigree data was consistent with a monogenic autosomal recessive pattern inheritance.

Conclusions: The study describes the clinical and pathological findings of lissencephaly with cerebellar hypoplasia in Churra lambs for which an autosomal recessive inheritance was the most likely cause. Histopathological features observed in the cerebral cortex and hippocampus are consistent with a possible failure in neuronal migration during brain development. This report suggests that lissencephaly should be considered in the differential diagnosis of congenital neurological disease in newborn lambs showing weakness, inability to walk and difficulty sucking.

Show MeSH
Related in: MedlinePlus