Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UMLS:C0153640 (Cerebellum)
 1,777 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

It was attempted to preserve the water distribution in central nervous tissue by rapid freezing followed by substitution fixation at low temperature. The vermis of the cerebellum of white mice was frozen by bringing it into contact with a polished silver mirror maintained at a temperature of about -207 degrees C. The tissue was subjected to substitution fixation in acetone containing 2 per cent OsO(4) at -85 degrees C for 2 days, and then prepared for electron microscopy by embedding in Maraglas, sectioning, and staining with lead citrate or uranyl acetate and lead. Cerebellum frozen within 30 seconds of circulatory arrest was compared with cerebellum frozen after 8 minutes' asphyxiation. From impedance measurements under these conditions, it could be expected that in the former tissue the electrolyte and water distribution is similar to that in the normal, oxygenated cerebellum, whereas in the asphyxiated tissue a transport of water and electrolytes into the intracellular compartment has taken place. Electron micrographs of tissue frozen shortly after circulatory arrest revealed the presence of an appreciable extracellular space between the axons of granular layer cells. Between glia, dendrites, and presynaptic endings the usual narrow clefts and even tight junctions were found. Also the synaptic cleft was of the usual width (250 to 300 A). In asphyxiated tissue, the extracellular space between the axons is either completely obliterated (tight junctions) or reduced to narrow clefts between apposing cell surfaces.
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PMID:A STUDY OF EXTRACELLULAR SPACE IN CENTRAL NERVOUS TISSUE BY FREEZE-SUBSTITUTION. 1428 23

Spinocerebellar ataxia-1 (SCA1) is a late onset neurodegenerative disease caused by the expansion of a polyglutamine repeat within ataxin-1 protein. The toxic effects triggered by mutant ataxin-1 result in degeneration of the neurons in cerebellum, brain stem and spinocerebellar tracts. The targeted overexpression of mutant ataxin-1 in cerebellar Purkinje cells (PCs) of the SCA1 transgenic mice results in the formation of cytoplasmic vacuoles in PCs. These vacuoles appear early on before the onset of behavioral abnormalities. Interestingly, we found that vacoules contain S100B and vimentin proteins, which normally localize to neighboring Bergmann glia (BG). Further, immunohistochemical and specialized silver stain analysis revealed that vacuolar formation is associated with alterations in the morphology of dendritic spines of PCs. To gain insights into the mechanisms of vacuolar formation, we investigated if vacuoles in SCA1 PCs have an autophagic origin or are a consequence of some other event. We examined the expression levels (by Western blotting) of microtubule-associated protein light chain 3 (LC3)-I and LC3-II, and the degradation levels of p62 (a LC3 partner) in the cerebellar fractions prepared from pre-symptomatic SCA1 and age-matched wild-type mice. No p62 degradation was observed; however, LC3-II/(LC3-I + LC3-II) ratios were significantly altered in SCA1 mice indicating changes in the autophagic flux. In addition, LC3 localized to PC vacuoles. Further, we observed a co-localization of myo-inositol monophosphatase 1 (IMPA1) with S100B in PC vacuoles. IMPA1 is present in PC spines and has been implicated in autophagy. In vitro studies using purified IMPA1 and S100B demonstrated that S100B interacted with and activated IMPA1. Both apo and Ca(2+)-bound S100B were found to activate IMPA1, depending on substrate concentration. IMPA1 is regulated by another calcium-binding protein calbindin-D28k (CaB), since we reported earlier that the CaB levels are reduced in SCA1 PCs, the activation of IMPA1 by S100B may modulate CaB-dependent inositol signaling. This may cause BG-PC interface to degenerate resulting in vacuolar formation. In sum, these data indicate that vacuoles appearing early in SCA1 PCs could be developing through some unknown autophagic mechanism.
Cerebellum 2009 Sep
PMID:Bergmann glial S100B activates myo-inositol monophosphatase 1 and Co-localizes to purkinje cell vacuoles in SCA1 transgenic mice. 1959 77

Until the end of 18th century, the role of the cerebellum remained obscure. The turning point occurred when Luigi Galvani showed that muscle contraction is due to electricity and Alessandro Volta produced the battery, an apparatus based on the pairing of silver and zinc plates separated by brine soaked paper disks, capable to generate electricity. Luigi Rolando, at beginning of 19th century, was impressed by these two observations. He thought that, since the brain generates the movement, it must contain a device generating electricity. As a battery, it should be formed by overlapping disks and the cerebellum for Rolando seemed to be the right structure for such a characteristic laminar organization. He argued that, if the cerebellum is the battery that produces electricity for muscle activity, its removal would produce paralysis. Consequently, Rolando removed the cerebellum in a young goat and observed that the animal, before dying, could no longer stand up. He concluded that the cerebellum is a motor structure as it generates the electricity which produces the movement. The conclusions of Rolando were criticized by Marie-Jean-Pierre Flourens who observed that animals undergoing cerebellectomy were still able to move, even if with problems of balance. Flourens concluded that the role of the cerebellum "is to put in order or to coordinate movements wanted by certain parts of the nervous system, excited by others". It was necessary to wait up to 1891 when Luigi Luciani, observing a dog survived the cerebellectomy, described a triad of symptoms (asthenia, atony and astasis), unquestionably of cerebellar origin.
Cerebellum Ataxias 2015
PMID:Where did the motor function of the cerebellum come from? 2633 Oct 53