scholarly journals Regulation by cytidine nucleotides of the acylation of sn-[14C]glycerol 3-phosphate. Regional and subcellular distribution of the enzymes responsible for phosphatidic acid synthesis de novo in the central nervous system of the rat

1973 ◽  
Vol 132 (3) ◽  
pp. 381-394 ◽  
Author(s):  
F. Possmayer ◽  
B. Meiners ◽  
J. B. Mudd

1. The regional and subcellular distribution of the incorporation of sn-[14C]glycerol 3-phosphate into rat brain lipids in vitro was investigated and compared with the relative specific activity of various chemical and enzyme markers. The similarity between the subcellular distribution of this incorporation and of NADPH-cytochrome c reductase activity indicated that the synthesis of phosphatidic acid via this route correlated with the presence of endoplasmic reticulum. 2. Experiments in which various amounts of the microsomal fraction were added to fixed amounts of nuclear, myelin, nerve-ending and mitochondrial preparations clearly demonstrated that the endoplasmic-reticulum contamination of these fractions was entirely responsible for the incorporation of sn-[14C]glycerol 3-phosphate. 3. The presence of CMP or CTP inhibited the incorporation of sn-[14C]glycerol 3-phosphate into the whole homogenate. Similar effects were observed with individual fractions, except for the mitochondria. With the mitochondrial fraction the effect of these cytidine nucleotides varied with the preparation, stimulating in some preparations and inhibiting with other preparations. The presence of CDP-choline stimulated the incorporation into the whole homogenate and to a lesser extent into the subcellular fractions. 4. These results indicate that the various organelles of the central nervous system are more dependent on endoplasmic reticulum for the production of glycerolipids de novo than has previously been appreciated.

1978 ◽  
Vol 56 (3) ◽  
pp. 535-538 ◽  
Author(s):  
S. W. Tang ◽  
H. C. Stancer ◽  
J. J. Warsh

A new strategy for measurement of brain catecholamines was tested in an animal model. [3H]Norepinephrine was infused intravenously in rabbits to label the peripheral norepinephrine pools. The specific activity of urinary 3-methoxy-4-hydroxymandelic acid was consistently higher than that for 3-methoxy-4-hydroxyphenylglycol (MHPG). Central sympathectomy with 6-hydroxydopamine abolished this difference. Using the formula we propose, it is estimated that 30–50% of urinary MHPG originates from the central nervous system.


2019 ◽  
Vol 34 (1) ◽  
Author(s):  
Vikas Sharma ◽  
S. Bhaskar ◽  
Sumit Ramdas Hire ◽  
Arvind Ahuja

Abstract Background Gangliogliomas are rare tumors of the central nervous system. They can occur anywhere in the central nervous system but are most commonly located in the temporal lobe and are mainly found in children. Anaplastic ganglioglioma can result from either de novo or transformation of a pre-existing lesion. Case presentation We report a case of de novo anaplastic ganglioglioma in the parieto occipital region, which is a rare location. A 34-year-old lady presented with features of raised intracranial pressure (ICP) with right side hemiparesis. Contrast-enhanced magnetic resonance imaging (CEMRI) of the brain showed well-defined intense heterogenously enhancing solid cystic mass lesion 5.3 × 5.2 cm in the left parieto occipital region with mass effect and midline shift. Intraoperatively, a cystic mass lesion with reddish brown nodule was seen in the left occipital lobe. Complete tumor excision was done. Microscopic and IHC examination was suggestive of anaplastic ganglioglioma. The post-operative period was uneventful. The patient received 60-Gy radiotherapy with temozolamide as adjuvant therapy, and repeat imaging showed no tumor recurrence. Conclusion Anaplastic gangliogliomas are rare tumors with parieto occipital as rare location.


2020 ◽  
Vol 17 (3) ◽  
pp. 1142-1152 ◽  
Author(s):  
Karl E. Carlström ◽  
Praveen K. Chinthakindi ◽  
Belén Espinosa ◽  
Faiez Al Nimer ◽  
Elias S. J. Arnér ◽  
...  

Abstract The Nrf2 transcription factor is a key regulator of redox reactions and considered the main target for the multiple sclerosis (MS) drug dimethyl fumarate (DMF). However, exploration of additional Nrf2-activating compounds is motivated, since DMF displays significant off-target effects and has a relatively poor penetrance to the central nervous system (CNS). We de novo synthesized eight vinyl sulfone and sulfoximine compounds (CH-1–CH-8) and evaluated their capacity to activate the transcription factors Nrf2, NFκB, and HIF1 in comparison with DMF using the pTRAF platform. The novel sulfoximine CH-3 was the most promising candidate and selected for further comparison in vivo and later an experimental model for traumatic brain injury (TBI). CH-3 and DMF displayed comparable capacity to activate Nrf2 and downstream transcripts in vitro, but with less off-target effects on HIF1 from CH-3. This was verified in cultured microglia and oligodendrocytes (OLs) and subsequently in vivo in rats. Following TBI, DMF lowered the number of leukocytes in blood and also decreased axonal degeneration. CH-3 preserved or increased the number of pre-myelinating OL. While both CH-3 and DMF activated Nrf2, CH-3 showed less off-target effects and displayed more selective OL associated effects. Further studies with Nrf2-acting compounds are promising candidates to explore potential myelin protective or regenerative effects in demyelinating disorders.


1981 ◽  
Vol 20 ◽  
pp. 307-313 ◽  
Author(s):  
Nicolás G. Bazán ◽  
Marta I. Aveldaño de Caldironi ◽  
Norma M. Giusto ◽  
Elena B. Rodríguez de Turco

Author(s):  
Paul Kleihues ◽  
Elisabeth Rushing ◽  
Hiroko Ohgaki

The revised fourth edition of the WHO classification of Tumours of the Central Nervous System, published in 2016, comprises several newly recognized tumour entities, and a significant restructuring of the classification, mainly based on genetic profiling. Glioblastomas are now classified into two major types. Isocitrate dehydrogenase (IDH)-wildtype glioblastoma (primary glioblastoma IDH-wildtype) develops rapidly de novo without a recognizable precursor lesion. IDH-mutant glioblastoma (secondary glioblastoma IDH-mutant) develops more slowly through malignant progression from diffuse or anaplastic astrocytoma. Medulloblastomas are now defined by combining histological patterns (classic, desmoplastic/nodular, extensive nodularity, anaplastic) and genetic hallmarks (WNT-activated; SHH-activated, TP53-mutant; SHH-activated, TP53-wildtype; non-WNT/non-SHH). Other newly recognized tumour entities include diffuse midline glioma, H3 K27M-mutant; ependymoma, RELA fusion-positive; and embryonal tumour with multilayered rosettes. The new classification is a significant step forward and will facilitate the development of novel targeted therapies of brain tumours.


Sign in / Sign up

Export Citation Format

Share Document