scholarly journals Investigation on Wntless to regulate dendritic development in cerebellar Purkinje cells

2017 ◽  
Vol 145 ◽  
pp. S60
Author(s):  
Yue Hu ◽  
Kin Ming Kwan
Keyword(s):  
Purkinje Cells ◽  
Dendritic Development ◽  
Cerebellar Purkinje Cells

Astrocytes-derived soluble factor promotes the survival and dendritic development of rat cerebellar Purkinje cells

1998 ◽  
Vol 31 ◽  
pp. S310
Author(s):  
Shigeki Furuya ◽  
Toshihide Tabata ◽  
Junya Mitoma ◽  
Asami Makino ◽  
Masanobu Kano ◽  
...  
Keyword(s):  
Purkinje Cells ◽  
Soluble Factor ◽  
Dendritic Development ◽  
Cerebellar Purkinje Cells

scholarly journals The Bacterial Enzyme RfxCas13d Is Less Neurotoxic Than PspCas13b and Could Be a Promising RNA Editing and Interference Tool in the Nervous System

2021 ◽  
Vol 11 (8) ◽  
pp. 1054
Author(s):  
Qin-Wei Wu ◽  
Josef P. Kapfhammer
Keyword(s):  
Nervous System ◽  
Purkinje Cells ◽  
Rna Editing ◽  
Neuronal Development ◽  
Neurological Diseases ◽  
Significant Inhibition ◽  
Great Promise ◽  
Bacterial Enzymes ◽  
Dendritic Development ◽  
Cerebellar Purkinje Cells

RNA therapies using RNA editing and interference are currently being developed for neurological diseases. The CRISPR-Cas13 system, based on bacterial enzymes, holds great promise for developing efficient tools for RNA therapies. However, neurotoxic activity has been reported for Cas13a, and recent studies have reported toxic effects of PspCas13b and RfxCas13d during zebrafish and Drosophila embryonic development. It is important to investigate the safety of these bacterial enzymes in the context of the nervous system and neuronal development. In this study, we used mouse cerebellar Purkinje cells as a complex neuron type to test for the potential neurotoxic actions of RfxCas13d and PspCas13b. We found that PspCas13b significantly impeded the dendritic development of cultured Purkinje cells, similar to the neurotoxic action of Cas13a. In contrast, RfxCas13d did not exhibit a significant inhibition of dendritic development. A similar trend was found for axonal outgrowth. These results suggest varying neurotoxic properties for different Cas13 ortholog enzymes. We call for more studies to investigate, and possibly mitigate, the neurotoxicity of Cas13 proteins in order to improve the safety of the CRISPR-Cas13 system for RNA therapies.

scholarly journals PKCγ-Mediated Phosphorylation of CRMP2 Regulates Dendritic Outgrowth in Cerebellar Purkinje Cells

2020 ◽  
Vol 57 (12) ◽  
pp. 5150-5166
Author(s):  
Sabine C. Winkler ◽  
Etsuko Shimobayashi ◽  
Josef P. Kapfhammer
Keyword(s):  
Purkinje Cell ◽  
Purkinje Cells ◽  
Synaptic Function ◽  
Mass Spectrometry Analysis ◽  
Spinocerebellar Ataxia Type ◽  
Proximity Ligation Assay ◽  
Wild Type ◽  
Dynamic Regulation ◽  
Dendritic Development ◽  
Cerebellar Purkinje Cells

Abstract The signalling protein PKCγ is a major regulator of Purkinje cell development and synaptic function. We have shown previously that increased PKCγ activity impairs dendritic development of cerebellar Purkinje cells. Mutations in the protein kinase Cγ gene (PRKCG) cause spinocerebellar ataxia type 14 (SCA14). In a transgenic mouse model of SCA14 expressing the human S361G mutation, Purkinje cell dendritic development is impaired in cerebellar slice cultures similar to pharmacological activation of PKC. The mechanisms of PKCγ-driven inhibition of dendritic growth are still unclear. Using immunoprecipitation-coupled mass spectrometry analysis, we have identified collapsin response mediator protein 2 (CRMP2) as a protein interacting with constitutive active PKCγ(S361G) and confirmed the interaction with the Duolink™ proximity ligation assay. We show that in cerebellar slice cultures from PKCγ(S361G)-mice, phosphorylation of CRMP2 at the known PKC target site Thr555 is increased in Purkinje cells confirming phosphorylation of CRMP2 by PKCγ. miRNA-mediated CRMP2 knockdown decreased Purkinje cell dendritic outgrowth in dissociated cerebellar cultures as did the transfection of CRMP2 mutants with a modified Thr555 site. In contrast, dendritic development was normal after wild-type CRMP2 overexpression. In a novel knock-in mouse expressing only the phospho-defective T555A-mutant CRMP2, Purkinje cell dendritic development was reduced in dissociated cultures. This reduction could be rescued by transfecting wild-type CRMP2 but only partially by the phospho-mimetic T555D-mutant. Our findings establish CRMP2 as an important target of PKCγ phosphorylation in Purkinje cells mediating its control of dendritic development. Dynamic regulation of CRMP2 phosphorylation via PKCγ is required for its correct function.

Ultrastorcture of Cerebellar Purkinje Cells in Rats Subjected To Partial Global Cerebral Ischemia

1985 ◽  
Vol 43 ◽  
pp. 674-675
Author(s):  
R.V.W. Dimlich ◽  
M.H. Biros
Keyword(s):  
Cerebral Ischemia ◽  
Purkinje Cells ◽  
Cell Types ◽  
Microscopic Level ◽  
Global Cerebral Ischemia ◽  
Light Microscopic Level ◽  
Cerebellar Damage ◽  
Cerebellar Injury ◽  
Cerebellar Purkinje Cells ◽  
Cell Changes

In severe cerebral ischemia, Purkinje cells of the cerebellum are one of the cell types most vulnerable to anoxic damage. In the partial (forebrain) global ischemic (PGI) model of the rat, Paljärvi noted at the light microscopic level that cerebellar damage is inconsistant and when present, milder than in the telencephalon, diencephalon and rostral brain stem. Cerebellar injury was observed in 3 of 4 PGI rats following 5 minutes of reperfusion but in none of the rats after 90 min of reperfusion. To evaluate a time between these two extremes (5 and 90 min), the present investigation used the PGI model to study the effects of ischemia on the ultrastructure of cerebellar Purkinje cells in rats that were sacrificed after 30 min of reperfusion. This time also was chosen because lactic acid that is thought to contribute to ischemic cell changes in PGI is at a maximum after 30 min of reperfusion.

Sign in / Sign up

Export Citation Format

Share Document