For many degenerative cerebellar diseases, currently, no effective treatment that would substantially restore cerebellar functions is available. Neurotransplantation could be a promising therapy for such cases. Nevertheless, there are still severe limitations for routine clinical use. The aim of the work was to assess volume and morphology and functional impact on motor skills of an embryonic cerebellar graft injected in the form of cell suspension in Lurcher mutant and wild-type mice of the B6CBA and C3H strains after a 6-month survival period. The grafts survived in the majority of the mice. In both B6CBA and C3H Lurcher mice, most of the grafts were strictly delimited with no tendency to invade the host cerebellum, while in wild-type mice, graft-derived Purkinje cells colonized the host's cerebellum. In C3H Lurcher mice, but not in B6CBA Lurchers, the grafts had smaller volume than in their wild-type counterparts. C3H wild-type mice had significantly larger grafts than B6CBA wild-type mice. No positive effect of the transplantation on performance in the rotarod test was observed. The findings suggest that the niche of the Lurcher mutant cerebellum has a negative impact on integration of grafted cells. This factor seems to be limiting for specific functional effects of the transplantation therapy in this mouse model of cerebellar degeneration.

Department of Histology and Embryology Faculty of Medicine in Pilsen Charles University Karlovarska 48 301 66 Plzen Czech Republic

Department of Pathophysiology Faculty of Medicine in Pilsen Charles University alej Svobody 1655 76 323 00 Plzen Czech Republic

Laboratory of Neurodegenerative Disorders Biomedical Center Faculty of Medicine in Pilsen Charles University alej Svobody 1655 76 323 00 Plzen Czech Republic

Laboratory of Quantitative Histology Biomedical Center Faculty of Medicine in Pilsen Charles University Karlovarska 48 301 66 Plzen Czech Republic

See more in PubMed

Nature. 1997 Aug 21;388(6644):769-73 PubMed

Behav Brain Res. 2014 Sep 1;271:218-27 PubMed

Neurosci Res. 1988 Dec;6(2):162-6 PubMed

Neuroscience. 1993 Jul;55(1):1-21 PubMed

J Microsc. 1999 Mar;193(Pt 3):199-211 PubMed

J Neurosci. 2006 Nov 8;26(45):11682-94 PubMed

Neurobiol Dis. 2010 Nov;40(2):415-23 PubMed

Vision Res. 2002 Feb;42(4):517-25 PubMed

Nat Rev Neurosci. 2002 May;3(5):401-9 PubMed

Rev Neurosci. 2015;26(1):75-93 PubMed

Exp Neurol. 1998 Dec;154(2):336-52 PubMed

Brain Res Mol Brain Res. 1998 Nov 20;62(2):224-7 PubMed

Neuroscience. 1987 Jan;20(1):1-22 PubMed

Neurology. 2015 Apr 28;84(17):1751-9 PubMed

Dev Biol. 2008 May 1;317(1):147-60 PubMed

Front Neuroanat. 2016 Apr 19;10:35 PubMed

Neurosci Lett. 2014 Jan 13;558:154-8 PubMed

Cerebellum. 2017 Apr;16(2):340-347 PubMed

Neurosci Res. 2003 May;46(1):11-22 PubMed

J Comp Neurol. 2002 Oct 28;452(4):311-23 PubMed

Cerebellum Ataxias. 2016 Apr 04;3:7 PubMed

J Comp Neurol. 2006 Aug 1;497(4):622-35 PubMed

J Neurosci. 2006 Jul 26;26(30):7839-48 PubMed

Nature. 1987 Jun 4-10;327(6121):421-3 PubMed

Cerebellum. 2015 Dec;14(6):632-41 PubMed

Ther Adv Neurol Disord. 2016 Sep;9(5):396-413 PubMed

Neuroreport. 2001 Oct 8;12(14):3039-43 PubMed

Proc Natl Acad Sci U S A. 2013 Mar 5;110(10):E948-57 PubMed

Stem Cells. 2010 Apr;28(4):821-31 PubMed

Eur J Neurosci. 2005 Sep;22(5):1001-12 PubMed

J Neurosci. 2009 May 27;29(21):7079-91 PubMed

J Comp Neurol. 2002 Jun 3;447(3):210-7 PubMed

Neuroendocrinology. 1997 Nov;66(5):341-7 PubMed

J Neurochem. 1990 Dec;55(6):1980-5 PubMed

Cell Transplant. 1996 Mar-Apr;5(2):269-77 PubMed

Neuroscientist. 2008 Feb;14(1):91-100 PubMed

Exp Neurol. 1999 Aug;158(2):301-11 PubMed

Anat Embryol (Berl). 1992;185(5):409-20 PubMed

J Comp Neurol. 2010 Jun 1;518(11):1892-907 PubMed

Anat Rec (Hoboken). 2009 Dec;292(12):1986-92 PubMed

CNS Neurol Disord Drug Targets. 2017 Aug 10;:null PubMed

Biochem Biophys Res Commun. 1993 Dec 30;197(3):1267-76 PubMed

Neurosci Lett. 2012 Apr 25;515(1):23-7 PubMed

Curr Neuropharmacol. 2011 Jun;9(2):313-7 PubMed

Prague Med Rep. 2006;107(1):89-94 PubMed

Philos Trans R Soc Lond B Biol Sci. 1979 Oct 11;287(1020):167-201 PubMed

Cerebellum. 2016 Feb;15(1):48-50 PubMed

Neuroreport. 1995 Oct 2;6(14):1827-32 PubMed

Dev Neurobiol. 2007 Jul;67(8):1032-46 PubMed

Cell. 1995 Apr 21;81(2):245-52 PubMed

J Neurosci. 2002 Aug 15;22(16):7132-46 PubMed

Nat Cell Biol. 2003 Nov;5(11):959-66 PubMed

Neurobiol Dis. 2017 Jun;102:49-59 PubMed

Brain. 2015 Feb;138(Pt 2):320-35 PubMed

Cerebellum. 2005;4(1):2-6 PubMed

Res Immunol. 1992 Jan;143(1):129-39 PubMed

Quantification of Solid Embryonic Cerebellar Graft Volume in a Degenerative Ataxia Model

Reduction of Microvessel Number and Length in the Cerebellum of Purkinje Cell Degeneration Mice

Consensus Paper: Strengths and Weaknesses of Animal Models of Spinocerebellar Ataxias and Their Clinical Implications

Hippocampal mitochondrial dysfunction and psychiatric-relevant behavioral deficits in spinocerebellar ataxia 1 mouse model

Embryonic Cerebellar Graft Morphology Differs in Two Mouse Models of Cerebellar Degeneration

Task Force Paper On Cerebellar Transplantation: Are We Ready to Treat Cerebellar Disorders with Cell Therapy?