Cerebellar cortex development in the weaver condition presents regional and age-dependent abnormalities without differences in Purkinje cells neurogenesis

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Acta Neurobiologiae Experimentalis

Nencki Institute of Experimental Biology

Subject: Behavioral Sciences, Biomedical Sciences & Nutrition, Life Sciences, Medicine, Neurosciences

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ISSN: 0065-1400
eISSN: 1689-0035

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VOLUME 76 , ISSUE 1 (March 2016) > List of articles

Cerebellar cortex development in the weaver condition presents regional and age-dependent abnormalities without differences in Purkinje cells neurogenesis

Joaquín Martí * / María C. Santa-Cruz / José P. Hervás / Shirley A. Bayer / Sandra Villegas *

Keywords : cerebellar ataxias, homozygous weaver mice, development, cerebellar lobes, morphometry, [3H]TdR autoradiography.

Citation Information : Acta Neurobiologiae Experimentalis. Volume 76, Issue 1, Pages 53-65, DOI: https://doi.org/10.21307/ane-2017-005

License : (CC BY 4.0)

Received Date : 21-June-2015 / Accepted: 11-March-2016 / Published Online: 06-October-2017

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ABSTRACT

Ataxias are neurological disorders associated with the degeneration of Purkinje cells (PCs). Homozygous weaver mice (wv/wv) have been proposed as a model for hereditary cerebellar ataxia because they present motor abnormalities and PC loss. To ascertain the physiopathology of the weaver condition, the development of the cerebellar cortex lobes was examined at postnatal day (P): P8, P20 and P90. Three approaches were used:
1) quantitative determination of several cerebellar features;
2) qualitative evaluation of the developmental changes occurring in the cortical lobes; and
3) autoradiographic analyses of PC generation and placement.
Our results revealed a reduction in the size of the wv/wv cerebellum as a whole, confirming previous results. However, as distinguished from these reports, we observed that quantified parameters contribute differently to the abnormal growth of the wv/wv cerebellar lobes. Qualitative analysis showed anomalies in wv/wv cerebellar cytoarchitecture, depending on the age and lobe analyzed. Such abnormalities included the presence of the external granular layer after P20 and, at P90, ectopic cells located in the molecular layer following several placement patterns. Finally, we obtained autoradiographic evidence that wild-type and wv/wv PCs presented similar neurogenetic timetables, as reported. However, the innovative character of this current work lies in the fact that the neurogenetic gradients of wv/wv PCs were not modified from P8 to P90. A tendency for the accumulation of late-formed PCs in the anterior and posterior lobes was found, whereas early-generated PCs were concentrated in the central and inferior lobes. These data suggested that wv/wv PCs may migrate properly to their final destinations. The extrapolation of our results to patients affected with cerebellar ataxias suggests that all cerebellar
cortex lobes are affected with several age-dependent alterations in cytoarchitectonics. We also propose that PC loss may be regionally variable and not related to their neurogenetic timetables.

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