Cbln1 downregulates the formation and function of inhibitory synapses in mouse cerebellar Purkinje cells

2014 ◽  
Vol 39 (8) ◽  
pp. 1268-1280 ◽  
Author(s):  
Aya Ito-Ishida ◽  
Wataru Kakegawa ◽  
Kazuhisa Kohda ◽  
Eriko Miura ◽  
Shigeo Okabe ◽  
...  
2019 ◽  
Vol 20 (7) ◽  
pp. 1797 ◽  
Author(s):  
Helena F. Pernice ◽  
Rico Schieweck ◽  
Mehrnoosh Jafari ◽  
Tobias Straub ◽  
Martin Bilban ◽  
...  

Staufen2 (Stau2) is an RNA-binding protein that is involved in dendritic spine morphogenesis and function. Several studies have recently investigated the role of Stau2 in the regulation of its neuronal target mRNAs, with particular focus on the hippocampus. Here, we provide evidence for Stau2 expression and function in cerebellar Purkinje cells. We show that Stau2 downregulation (Stau2GT) led to an increase of glutamate receptor ionotropic delta subunit 2 (GluD2) in Purkinje cells when animals performed physical activity by voluntary wheel running compared with the age-matched wildtype (WT) mice (C57Bl/6J). Furthermore, Stau2GT mice showed lower performance in motor coordination assays but enhanced motor learning abilities than did WT mice, concomitantly with an increase in dendritic GluD2 expression. Together, our results suggest the novel role of Stau2 in Purkinje cell synaptogenesis in the mouse cerebellum.


2011 ◽  
Vol 589 (14) ◽  
pp. 3433-3440 ◽  
Author(s):  
Eric Hosy ◽  
Claire Piochon ◽  
Eva Teuling ◽  
Lorenzo Rinaldo ◽  
Christian Hansel

2005 ◽  
Vol 82 (2) ◽  
pp. 172-183 ◽  
Author(s):  
Yumiko Shimazaki ◽  
Isao Nagata ◽  
Maki Ishii ◽  
Masahiko Tanaka ◽  
Tohru Marunouchi ◽  
...  

2019 ◽  
Vol 9 (4) ◽  
pp. 80 ◽  
Author(s):  
Belozor ◽  
Yakovleva ◽  
Potapenko ◽  
Shuvaev ◽  
Smolnikova ◽  
...  

Astrogliosis is a pathological process that affects the density, morphology, and function of astrocytes. It is a common feature of brain trauma, autoimmune diseases, and neurodegeneration including spinocerebellar ataxia type 1 (SCA1), a poorly understood neurodegenerative disease. S100β is a Ca2+ binding protein. In SCA1, excessive excretion of S100β by reactive astrocytes and its uptake by Purkinje cells has been demonstrated previously. Under pathological conditions, excessive extracellular concentration of S100β stimulates the production of proinflammatory cytokines and induces apoptosis. We modeled astrogliosis by S100β injections into cerebellar cortex in mice. Injections of S100β led to significant changes in Bergmann glia (BG) cortical organization and affected their processes. S100β also changed morphology of the Purkinje cells (PCs), causing a significant reduction in the dendritic length. Moreover, the short-term synaptic plasticity and depolarization-induced suppression of synaptic transmission were disrupted after S100β injections. We speculate that these effects are the result of Ca2+-chelating properties of S100β protein. In summary, exogenous S100β induced astrogliosis in cerebellum could lead to neuronal dysfunction, which resembles a natural neurodegenerative process. We suggest that astrocytes play an essential role in SCA1 pathology, and that astrocytic S100β is an important contributor to this process.


2018 ◽  
Vol 13 (6) ◽  
pp. 1019 ◽  
Author(s):  
Lai Wang ◽  
Jin-Bo Deng ◽  
Wen-Juan Fan ◽  
Ming-Chao Yan ◽  
Yi-Zheng Sun ◽  
...  

2021 ◽  
Author(s):  
Zhihui Liu ◽  
Man Jiang ◽  
Kif Liakath-Ali ◽  
Jaewon Ko ◽  
Roger Shen Zhang ◽  
...  

Cadherins contribute to the organization of nearly all tissues, but the functions of several evolutionarily conserved cadherins, including those of calsyntenins, remain enigmatic. Puzzlingly, two distinct, non-overlapping functions for calsyntenins were proposed: As postsynaptic neurexin ligands in synapse formation, or as presynaptic adaptors for kinesin-mediated vesicular transport. Here, we show that acute CRISPR-mediated deletion of calsyntenin-3 in cerebellar Purkinje cells in vivo causes a large decrease in inhibitory synapses, but a surprisingly robust increase in excitatory parallel-fiber synapses. No changes in the dendritic architecture of Purkinje cells or in climbing-fiber synapses were detected. Thus, by promoting formation of an excitatory type of synapses and decreasing formation of an inhibitory type of synapses in the same neuron, calsyntenin-3 functions as a postsynaptic adhesion molecule that regulates the excitatory/inhibitory balance in Purkinje cells. No similarly opposing function of a synaptic adhesion molecule was previously observed, suggesting a new paradigm of synaptic regulation.


Author(s):  
R.V.W. Dimlich ◽  
M.H. Biros

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