scholarly journals Central nervous system: cholesterol turnover, brain development and neurodegeneration

2009 ◽  
Vol 390 (4) ◽  
Author(s):  
John M. Dietschy
Keyword(s):  
Central Nervous System ◽  
Nervous System ◽  
Body Weight ◽  
Brain Development ◽  
Cholesterol Synthesis ◽  
De Novo ◽  
Brain Size ◽  
Average Amount ◽  
Early Brain Development ◽  
The Central Nervous System

Abstract The average amount of cholesterol in the whole animal equals approximately 2100 mg/kg body weight, and 15% and 23% of this sterol in the mouse and human, respectively, is found in the central nervous system. There is no detectable uptake across the blood-brain barrier of cholesterol carried in lipoproteins in the plasma, even in the newborn. However, high rates of de novo cholesterol synthesis in the glia and neurons provide the sterol necessary for early brain development. Once a stable brain size is achieved in the adult, cholesterol synthesis continues, albeit at a much lower rate, and this synthesis is just balanced by the excretion of an equal amount of sterol, either as 24(S)-hydroxycholesterol or, presumably, as cholesterol itself.

Bone-brain crosstalk and potential associated diseases

2016 ◽  
Vol 28 (2) ◽  
Author(s):  
Audrey Rousseaud ◽  
Stephanie Moriceau ◽  
Mariana Ramos-Brossier ◽  
Franck Oury
Keyword(s):  
Central Nervous System ◽  
Nervous System ◽  
Brain Development ◽  
Cognitive Functions ◽  
Intimate Relationship ◽  
Whole Body ◽  
Reciprocal Relationships ◽  
Skeletal Homeostasis ◽  
The Central Nervous System ◽  
The Brain

AbstractReciprocal relationships between organs are essential to maintain whole body homeostasis. An exciting interplay between two apparently unrelated organs, the bone and the brain, has emerged recently. Indeed, it is now well established that the brain is a powerful regulator of skeletal homeostasis via a complex network of numerous players and pathways. In turn, bone via a bone-derived molecule, osteocalcin, appears as an important factor influencing the central nervous system by regulating brain development and several cognitive functions. In this paper we will discuss this complex and intimate relationship, as well as several pathologic conditions that may reinforce their potential interdependence.

scholarly journals Tuberin levels during cellular differentiation in brain development

2021 ◽  
Author(s):  
Bashaer Abu Khatir ◽  
Gordon Omar Davis ◽  
Mariam Sameem ◽  
Rutu Patel ◽  
Jackie Fong ◽  
...  
Keyword(s):  
Central Nervous System ◽  
Nervous System ◽  
Brain Development ◽  
Cell Lines ◽  
Neural Development ◽  
Time Course ◽  
Embryonic Mouse ◽  
Organ Systems ◽  
The Central Nervous System

Tuberin is a member of a large protein complex, Tuberous Sclerosis Complex, and acts as a sensor for nutrient status regulating protein synthesis and cell cycle progression. Mutations in the Tuberin gene, TSC2, lead to the formation of tumors and developmental defects in many organ systems, including the central nervous system. Tuberin is expressed in the brain throughout development and levels of Tuberin have been found to decrease during neuronal differentiation in cell lines in vitro. Our current work investigates the levels of Tuberin at two stages of embryonic development in vivo, and we study the mRNA and protein levels during a time course using immortalized cell lines in vitro. Our results show that Tuberin levels remain stable in the olfactory bulb but decrease in the Purkinje cell layer during embryonic mouse brain development. We show here that Tuberin levels are higher when cells are cultured as neurospheres, and knockdown of Tuberin results in a reduction in the number of neurospheres. These data provide support for the hypothesis that Tuberin is an important regulator of stemness and the reduction of Tuberin levels might support functional differentiation in the central nervous system. Understanding how Tuberin expression is regulated throughout neural development is essential to fully comprehend the role of this protein in several developmental and neural pathologies.

scholarly journals A case report of rare location of ganglioglioma

2019 ◽  
Vol 34 (1) ◽  
Author(s):  
Vikas Sharma ◽  
S. Bhaskar ◽  
Sumit Ramdas Hire ◽  
Arvind Ahuja
Keyword(s):  
Central Nervous System ◽  
Nervous System ◽  
De Novo ◽  
Occipital Lobe ◽  
Cystic Mass ◽  
Mass Lesion ◽  
Occipital Region ◽  
Rare Tumors ◽  
Rare Location ◽  
The Central Nervous System

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.

scholarly journals Characterization of More Selective Central Nervous System Nrf2-Activating Novel Vinyl Sulfoximine Compounds Compared to Dimethyl Fumarate

2020 ◽  
Vol 17 (3) ◽  
pp. 1142-1152 ◽  
Author(s):  
Karl E. Carlström ◽  
Praveen K. Chinthakindi ◽  
Belén Espinosa ◽  
Faiez Al Nimer ◽  
Elias S. J. Arnér ◽  
...  
Keyword(s):  
Central Nervous System ◽  
Nervous System ◽  
De Novo ◽  
Dimethyl Fumarate ◽  
The Novel ◽  
The Central Nervous System ◽  
Demyelinating Disorders ◽  
Target Effects

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.

scholarly journals Conditional Mutation of Rb Causes Cell Cycle Defects without Apoptosis in the Central Nervous System

2003 ◽  
Vol 23 (3) ◽  
pp. 1044-1053 ◽  
Author(s):  
D. MacPherson ◽  
J. Sage ◽  
D. Crowley ◽  
A. Trumpp ◽  
R. T. Bronson ◽  
...  
Keyword(s):  
Cell Cycle ◽  
Central Nervous System ◽  
Nervous System ◽  
Muscle Development ◽  
Brain Size ◽  
Targeted Disruption ◽  
Show Evidence ◽  
The Central Nervous System ◽  
P53 Activation ◽  
Phase Entry

ABSTRACT Targeted disruption of the retinoblastoma gene in mice leads to embryonic lethality in midgestation accompanied by defective erythropoiesis. Rb −/− embryos also exhibit inappropriate cell cycle activity and apoptosis in the central nervous system (CNS), peripheral nervous system (PNS), and ocular lens. Loss of p53 can prevent the apoptosis in the CNS and lens; however, the specific signals leading to p53 activation have not been determined. Here we test the hypothesis that hypoxia caused by defective erythropoiesis in Rb-null embryos contributes to p53-dependent apoptosis. We show evidence of hypoxia in CNS tissue from Rb −/− embryos. The Cre-loxP system was then used to generate embryos in which Rb was deleted in the CNS, PNS and lens, in the presence of normal erythropoiesis. In contrast to the massive CNS apoptosis in Rb-null embryos at embryonic day 13.5 (E13.5), conditional mutants did not have elevated apoptosis in this tissue. There was still significant apoptosis in the PNS and lens, however. Rb −/− cells in the CNS, PNS, and lens underwent inappropriate S-phase entry in the conditional mutants at E13.5. By E18.5, conditional mutants had increased brain size and weight as well as defects in skeletal muscle development. These data support a model in which hypoxia is a necessary cofactor in the death of CNS neurons in the developing Rb mutant embryo.

scholarly journals Oestrogenic effects of neonatal administration of raloxifene on hypothalamic-pituitary-gonadal axis in male and female rats

Reproduction ◽  
2001 ◽  
pp. 915-924 ◽  
Author(s):  
L Pinilla ◽  
LC Gonzalez ◽  
F Gaytan ◽  
M Tena-Sempere ◽  
E Aguilar
Keyword(s):  
Central Nervous System ◽  
Nervous System ◽  
Body Weight ◽  
Oestrogen Receptor ◽  
Female Rats ◽  
Male Rats ◽  
Selective Oestrogen Receptor Modulators ◽  
Male And Female Rats ◽  
The Central Nervous System ◽  
Neonatal Administration

Selective oestrogen receptor modulators constitute a family of drugs that are used increasingly in the management of oestrogen-associated pathology. Raloxifene is a selective oestrogen receptor modulator that is used to treat and prevent osteoporosis in post-menopausal women. The actions of raloxifene on bone, breast, uterus and serum cholesterol concentrations have been widely analysed, but very few studies have investigated the possible actions of this drug on the central nervous system. The central nervous system of the newborn rat is very sensitive to oestrogen action. In this study a series of experiments was conducted to analyse the effects of different doses of raloxifene (50, 100, 250 or 500 microg per rat per day) administered to neonatal rats on days 1-5 of age. Female rats treated with raloxifene showed decreased gonadotrophin secretion, hyperprolactinaemia, advanced vaginal opening, decreased body weight, persistent presence of cornified epithelial cells in vaginal smears, anovulation, inhibition of positive feedback between oestradiol and LH, and infertility. Male rats showed delayed balanopreputial separation, reduced body weight and hyperprolactinaemia. All these changes resemble those obtained after neonatal administration of oestradiol benzoate, thus indicating, for the first time, that raloxifene exerts an oestrogenic action on the hypothalamic-pituitary structures controlling reproductive function in rats.

Insulin: its relationship to the central nervous system and to the control of food intake and body weight

1985 ◽  
Vol 42 (5) ◽  
pp. 1063-1071 ◽  
Author(s):  
S C Woods ◽  
D Porte ◽  
E Bobbioni ◽  
E Ionescu ◽  
J F Sauter ◽  
...  
Keyword(s):  
Central Nervous System ◽  
Nervous System ◽  
Body Weight ◽  
Food Intake ◽  
The Central Nervous System

scholarly journals Alendronate lowers cholesterol synthesis in the central nervous system of rats – a preliminary study

2009 ◽  
pp. 455-458 ◽  
Author(s):  
Ľ Cibičková ◽  
R Hyšpler ◽  
N Cibiček ◽  
E Čermáková ◽  
V Palička
Keyword(s):  
Spinal Cord ◽  
Central Nervous System ◽  
Nervous System ◽  
Frontal Cortex ◽  
Cholesterol Synthesis ◽  
Plasma Cholesterol ◽  
Cholesterol Biosynthesis ◽  
Experimental Treatment ◽  
Deuterated Water ◽  
The Central Nervous System

Nitrogen-containing bisphosphonates were found to inhibit farnesyl diphosphate synthase - an essential enzyme in the cholesterol biosynthesis pathway, but their effect on cholesterol synthesis per se in the central nervous system (CNS) remains unknown. The aim of the present study was to examine possible influence of a representative agent alendronate on cholesterol synthesis rates in selected parts of rat CNS and on plasma cholesterol level. Two groups of rats were orally administered either alendronate (3 mg/kg b.w.) or vehicle for 9 days. At the end of experiment, brain (basal ganglia, frontal cortex and hippocampus) and spinal cord were isolated and cholesterol synthesis was determined using the technique of deuterium incorporation from deuterated water. In the alendronate group significant reductions of cholesterol synthesis rates were detected in frontal cortex, hippocampus and spinal cord (p<0.001). However, the experimental treatment did not produce a significant alteration in the levels of plasma cholesterol. In conclusion, this study brings the first experimental evidence of the inhibition of cholesterol biosynthesis with alendronate in central nervous system.

The 2016 revision of the WHO classification of tumours of the central nervous system

2017 ◽  
Author(s):  
Paul Kleihues ◽  
Elisabeth Rushing ◽  
Hiroko Ohgaki
Keyword(s):  
Central Nervous System ◽  
Nervous System ◽  
Who Classification ◽  
De Novo ◽  
Genetic Profiling ◽  
Primary Glioblastoma ◽  
System P ◽  
Significant Step ◽  
The Central Nervous System

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.

Pharmacogenomics and pharmacokinetics of efavirenz 400 or 600 mg in 184 treatment-naive HIV-infected patients in China

2020 ◽  
Vol 21 (13) ◽  
pp. 945-956
Author(s):  
Rong Chen ◽  
Jun Chen ◽  
Jingna Xun ◽  
Zhiliang Hu ◽  
Qiong Huang ◽  
...  
Keyword(s):  
Central Nervous System ◽  
Nervous System ◽  
Body Weight ◽  
Plasma Levels ◽  
Dose Group ◽  
Adverse Reactions ◽  
Standard Dose ◽  
Treatment Naïve ◽  
The Central Nervous System ◽  
To Receive

Background: The pharmacogenomics and pharmacokinetics/pharmacodynamics of 400 mg efavirenz have rarely been reported. Materials & methods: A total of 184 treatment-naive HIV-infected patients were randomly assigned (1:1) to receive a lower dose (tenofovir disoproxil 200 mg, efavirenz 400 mg and lamivudine) or a standard dose regimen. Relationships between pharmacogenomics and efavirenz pharmacokinetics/pharmacodynamics were explored at 48 weeks. Results: There was no relationship between pharmacogenomics and adverse reactions of the central nervous system and antiretoviral efficacy. CYP2B6 516G>T, 785A>G, 18492C>T and ABCB1 3435C>T T/C were associated with higher efavirenz plasma levels in the standard but not the lower dose group. No relationship was found between pharmacogenomics and antiretoviral efficacy. Patients who were <60 kg had higher efavirenz concentration compared with those with weight ≥60 kg when using 600 mg efavirenz, this was not observed with 400 mg efavirenz. Conclusion: The effect of pharmacogenomics and body weight on the efavirenz concentration was significant in the 600 mg group but not in the 400 mg group.

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