scholarly journals Distribution and Cellular Localization of Prostacyclin Synthase in Human Brain

2000 ◽  
Vol 48 (5) ◽  
pp. 631-641 ◽  
Author(s):  
Isabel Siegle ◽  
Thomas Klein ◽  
Ming-Hui Zou ◽  
Peter Fritz ◽  
Martin Kömhoff
Keyword(s):  
Human Brain ◽  
Blood Vessels ◽  
Cellular Localization ◽  
Regional Distribution ◽  
Pyramidal Cells ◽  
Brain Homogenate ◽  
The Central Nervous System ◽  
Prostacyclin Synthase

SUMMARY Prostacyclin (PGI2) is a labile, lipid-derived metabolite of arachidonic acid synthesized through the sequential action of cyclo-oxygenase (COX) and prostacyclin synthase (PGIS). In addition to its well-characterized vasodilatory and thrombolytic effects, an increasing number of studies report an important role of PGI2 in nociception in various animal species. In this study we investigated the regional distribution of PGIS in human brain by immunohistochemistry and in situ hybridization. PGIS-immunoreactive (ir) protein was localized to blood vessels throughout the brain. Neuronal cells and glial cells, such as microglia and oligodendrocytes, also showed intense labeling. The strongest expression of PGIS was seen in large principal neurons, such as pyramidal cells of the cortex, pyramidal cells of the hippocampus, and Purkinje cells of the cerebellum. Abundance of PGIS mRNA was observed in blood vessels and large neurons and correlated well with the immunohistochemical findings. The expression of PGIS in human brain was further demonstrated by immunoblotting and detection of 6-keto-PGF1α, the stable degradation product of prostacyclin in human brain homogenate. These results demonstrate a widespread expression of PGIS in the central nervous system and suggest a potentially important role of prostacylin in modulating neuronal activity in human brain.

scholarly journals Identification of Type VI Collagen Synthesizing Cells in Human Diabetic Glomerulosclerosis Using Renal Biopsy Sections

1997 ◽  
Vol 15 (3) ◽  
pp. 175-181 ◽  
Author(s):  
Mohammed Shawkat Razzaque ◽  
Takehiko Koji ◽  
Takashi Harada ◽  
Takashi Taguchi
Keyword(s):  
Renal Biopsy ◽  
Cellular Localization ◽  
Oligonucleotide Probes ◽  
Diabetic Glomerulosclerosis ◽  
Type Vi Collagen ◽  
Cellular Origin ◽  
Collagen Mrna ◽  
Nodular Lesions

Although the role of extracellular matrices in the development of glomerulosclerosis has been discussed widely, the cellular origin of type VI collagen in diabetic nephropathy (DN) has remained relatively unexplored. This study reports the distribution and cellular origin of type VI collagen in DN. Type VI collagen‐specific oligonucleotide probes and monoclonal antibody were used to assess the relative expression of mRNA for \alpha1 (VI) chain and its translated protein in paraffin‐embedded renal biopsy sections of DN. By immunohistochemistry, compared to the control, increased deposition of type VI collagen was noted in the diffuse and nodular lesions of diabetic glomeruli. For cellular localization of type VI collagen mRNA, paraffin‐embedded renal sections of the control and DN were hybridizedin situwith digoxigenin (Dig)‐labeled antisense oligo‐DNA probe complementary to a part of \alpha1 (VI) mRNA. In comparison to the control kidney sections, increased numbers of intraglomerular cells (both mesangial and epithelial cells) were positive forα1 (VI) mRNA in renal biopsy sections of DN. From the results, we conclude that overexpression of type VI collagen by intraglomerular cells with its increased deposition might significantly contribute to the glomerulosclerosis found in DN.

Cellular localization and regional distribution of CYP2D6 mRNA and protein expression in human brain

2001 ◽  
Vol 11 (3) ◽  
pp. 237-245 ◽  
Author(s):  
Isabel Siegle ◽  
Peter Fritz ◽  
Klaus Eckhardt ◽  
Ulrich M. Zanger ◽  
Michel Eichelbaum
Keyword(s):  
Protein Expression ◽  
Human Brain ◽  
Cellular Localization ◽  
Regional Distribution ◽  
Mrna And Protein Expression

scholarly journals The Contribution of Microglia to the Development and Maturation of the Visual System

2021 ◽  
Vol 15 ◽  
Author(s):  
Michael A. Dixon ◽  
Ursula Greferath ◽  
Erica L. Fletcher ◽  
Andrew I. Jobling
Keyword(s):  
Central Nervous System ◽  
Nervous System ◽  
Visual System ◽  
Blood Vessels ◽  
Neural Function ◽  
Neural Signals ◽  
Quiescent Cells ◽  
The Central Nervous System ◽  
Vascular Plexuses

Microglia, the resident immune cells of the central nervous system (CNS), were once considered quiescent cells that sat in readiness for reacting to disease and injury. Over the last decade, however, it has become clear that microglia play essential roles in maintaining the normal nervous system. The retina is an easily accessible part of the central nervous system and therefore much has been learned about the function of microglia from studies in the retina and visual system. Anatomically, microglia have processes that contact all synapses within the retina, as well as blood vessels in the major vascular plexuses. Microglia contribute to development of the visual system by contributing to neurogenesis, maturation of cone photoreceptors, as well as refining synaptic contacts. They can respond to neural signals and in turn release a range of cytokines and neurotrophic factors that have downstream consequences on neural function. Moreover, in light of their extensive contact with blood vessels, they are also essential for regulation of vascular development and integrity. This review article summarizes what we have learned about the role of microglia in maintaining the normal visual system and how this has helped in understanding their role in the central nervous system more broadly.

scholarly journals Dynamic Role of Phospholipases A2 in Health and Diseases in the Central Nervous System

Cells ◽  
2021 ◽  
Vol 10 (11) ◽  
pp. 2963
Author(s):  
Grace Y. Sun ◽  
Xue Geng ◽  
Tao Teng ◽  
Bo Yang ◽  
Michael K. Appenteng ◽  
...  
Keyword(s):  
Central Nervous System ◽  
Nervous System ◽  
Cellular Localization ◽  
Cell Types ◽  
Molecular Structures ◽  
Specific Cell ◽  
Phospholipases A2 ◽  
Cell Functions ◽  
The Central Nervous System

Phospholipids are major components in the lipid bilayer of cell membranes. These molecules are comprised of two acyl or alkyl groups and different phospho-base groups linked to the glycerol backbone. Over the years, substantial interest has focused on metabolism of phospholipids by phospholipases and the role of their metabolic products in mediating cell functions. The high levels of polyunsaturated fatty acids (PUFA) in the central nervous system (CNS) have led to studies centered on phospholipases A2 (PLA2s), enzymes responsible for cleaving the acyl groups at the sn-2 position of the phospholipids and resulting in production of PUFA and lysophospholipids. Among the many subtypes of PLA2s, studies have centered on three major types of PLA2s, namely, the calcium-dependent cytosolic cPLA2, the calcium-independent iPLA2 and the secretory sPLA2. These PLA2s are different in their molecular structures, cellular localization and, thus, production of lipid mediators with diverse functions. In the past, studies on specific role of PLA2 on cells in the CNS are limited, partly because of the complex cellular make-up of the nervous tissue. However, understanding of the molecular actions of these PLA2s have improved with recent advances in techniques for separation and isolation of specific cell types in the brain tissue as well as development of sensitive molecular tools for analyses of proteins and lipids. A major goal here is to summarize recent studies on the characteristics and dynamic roles of the three major types of PLA2s and their oxidative products towards brain health and neurological disorders.

scholarly journals Regulation of the Brain Neural Niche by Soluble Molecule Akhirin

2021 ◽  
Vol 9 (3) ◽  
pp. 29
Author(s):  
Mikiko Kudo ◽  
Kunimasa Ohta
Keyword(s):  
Spinal Cord ◽  
Blood Vessels ◽  
Molecular Mechanisms ◽  
Neural Progenitor Cells ◽  
Central Canal ◽  
Neural Cells ◽  
Neural Tissues ◽  
The Central Nervous System ◽  
The Brain

In the central nervous system (CNS), which comprises the eyes, spinal cord, and brain, neural cells are produced by the repeated division of neural stem cells (NSCs) during the development of the CNS. Contrary to the notion that the CNS is relatively static with a limited cell turnover, cells with stem cell-like properties have been isolated from most neural tissues. The microenvironment, also known as the NSC niche, consists of NSCs/neural progenitor cells, other neurons, glial cells, and blood vessels; this niche is thought to regulate neurogenesis and the differentiation of NSCs into neurons and glia. Although it has been established that neurons, glia, and blood vessels interact with each other in a complex manner to generate neural tissues in the NSC niche, the underlying molecular mechanisms in the CNS niche are unclear. Herein, we would like to introduce the extracellular secreted protein, Akhirin (AKH; Akhi is the Bengali translation for eye). AKH is specifically expressed in the CNS niche—the ciliary body epithelium in the retina, the central canal of the spinal cord, the subventricular zone, and the subgranular zone of the dentate gyrus of the hippocampus—and is supposedly involved in NSC niche regulation. In this review, we discuss the role of AKH as a niche molecule during mouse brain formation.

scholarly journals MicroRNA Biomarkers in IBD—Differential Diagnosis and Prediction of Colitis-Associated Cancer

2020 ◽  
Vol 21 (21) ◽  
pp. 7893 ◽  
Author(s):  
Jaslin P. James ◽  
Lene Buhl Riis ◽  
Mikkel Malham ◽  
Estrid Høgdall ◽  
Ebbe Langholz ◽  
...  
Keyword(s):  
Differential Diagnosis ◽  
Cellular Localization ◽  
Predictive Biomarkers ◽  
Unknown Etiology ◽  
Treatment Protocols ◽  
Circulating Micrornas ◽  
Microarray Profiling ◽  
Inflammatory Bowel

Inflammatory bowel disease (IBD) includes Crohn’s disease (CD) and ulcerative colitis (UC). These are chronic autoimmune diseases of unknown etiology affecting the gastrointestinal tract. The IBD population includes a heterogeneous group of patients with varying disease courses requiring personalized treatment protocols. The complexity of the disease often delays the diagnosis and the initiation of appropriate treatments. In a subset of patients, IBD leads to colitis-associated cancer (CAC). MicroRNAs are single-stranded regulatory noncoding RNAs of 18 to 22 nucleotides with putative roles in the pathogenesis of IBD and colorectal cancer. They have been explored as biomarkers and therapeutic targets. Both tissue-derived and circulating microRNAs have emerged as promising biomarkers in the differential diagnosis and in the prognosis of disease severity of IBD as well as predictive biomarkers in drug resistance. In addition, knowledge of the cellular localization of differentially expressed microRNAs is a prerequisite for deciphering the biological role of these important epigenetic regulators and the cellular localization may even contribute to an alternative repertoire of biomarkers. In this review, we discuss findings based on RT-qPCR, microarray profiling, next generation sequencing and in situ hybridization of microRNA biomarkers identified in the circulation and in tissue biopsies.

New aspects of the role of histamine in cardiovascular function: identification, characterization, and potential pathophysiological importance of H3 receptors

1995 ◽  
Vol 73 (5) ◽  
pp. 558-564 ◽  
Author(s):  
M. Göthert ◽  
E. Schlicker ◽  
M. Garbarg ◽  
J.-C. Schwartz ◽  
J. A. Hey ◽  
...  
Keyword(s):  
Central Nervous System ◽  
Nervous System ◽  
Blood Vessels ◽  
Dura Mater ◽  
Noradrenaline Release ◽  
Vascular Function ◽  
Neurogenic Inflammation ◽  
Receptor Agonists ◽  
The Central Nervous System

As a result of intensive research during several decades, the distribution, function, and pathophysiological role of cardiovascular H1 and H2 receptors are well known, whereas reports on the occurrence and function of H3 receptors in blood vessels and the heart have not become available before the last 7 years (i.e., 4 years after the first description of these receptors in the central nervous system in 1983). The development of selective and potent H3 receptor agonists and antagonists was a prerequisite for convenient investigations of cardiovascular H3 receptors, which like H1 and H2 receptors are G-protein coupled but unlike them have not yet been cloned. Both in blood vessels and the heart, H3 receptors are located on noradrenergic nerve endings and upon stimulation mediate an inhibition of noradrenaline release. Whereas it remains to be clarified under which conditions the vascular H3 receptors may be stimulated by endogenous histamine, those in the heart become activated in the early phases of myocardial ischemia characterized by an increased histamine spillover. The H3 receptors in the central nervous system also appear to be of importance for the control of vascular function. Inhibitory presynaptic H3 receptors occur on trigeminal sensory C fibres supplying blood vessels in the dura mater. Release of neuropeptides from these fibres induces a neurogenic inflammation, which has been suggested to be involved in the pathogenesis of migraine. An interaction, involving presynaptic H3 receptors, between sensory C fibres and mast ceils in close apposition to these fibres plays a role in the control of histamine synthesis in the dura mater. By influencing this regulatory process, H3 receptor agonists may limit the extent of the neurogenic inflammation involved in the pathophysiology of migraine.Key words: histamine receptors, H3 receptors, presynaptic receptors, noradrenaline release, migraine.

scholarly journals Exogenous Aβ seeds induce Aβ depositions in the blood vessels rather than the brain parenchyma, independently of Aβ strain-specific information

2021 ◽  
Vol 9 (1) ◽  
Author(s):  
Tsuyoshi Hamaguchi ◽  
Jee Hee Kim ◽  
Akane Hasegawa ◽  
Ritsuko Goto ◽  
Kenji Sakai ◽  
...  
Keyword(s):  
Human Brain ◽  
Blood Vessels ◽  
Brain Homogenate ◽  
Brain Parenchyma ◽  
Brain Extract ◽  
Amyloid Angiopathy ◽  
Specific Information ◽  
Brain Extracts ◽  
Iatrogenic Transmission ◽  
The Brain

AbstractLittle is known about the effects of parenchymal or vascular amyloid β peptide (Aβ) deposition in the brain. We hypothesized that Aβ strain-specific information defines whether Aβ deposits on the brain parenchyma or blood vessels. We investigated 12 autopsied patients with different severities of Aβ plaques and cerebral amyloid angiopathy (CAA), and performed a seeding study using an Alzheimer’s disease (AD) mouse model in which brain homogenates derived from the autopsied patients were injected intracerebrally. Based on the predominant pathological features, we classified the autopsied patients into four groups: AD, CAA, AD + CAA, and less Aβ. One year after the injection, the pathological and biochemical features of Aβ in the autopsied human brains were not preserved in the human brain extract-injected mice. The CAA counts in the mice injected with all four types of human brain extracts were significantly higher than those in mice injected with PBS. Interestingly, parenchymal and vascular Aβ depositions were observed in the mice that were injected with the human brain homogenate from the less Aβ group. The Aβ and CAA seeding activities, which had significant positive correlations with the Aβ oligomer ratio in the human brain extracts, were significantly higher in the human brain homogenate from the less Aβ group than in the other three groups. These results indicate that exogenous Aβ seeds from different Aβ pathologies induced Aβ deposition in the blood vessels rather than the brain parenchyma without being influenced by Aβ strain-specific information, which might be why CAA is a predominant feature of Aβ pathology in iatrogenic transmission cases. Furthermore, our results suggest that iatrogenic transmission of Aβ pathology might occur due to contamination of brain tissues from patients with little Aβ pathology, and the development of inactivation methods for Aβ seeding activity to prevent iatrogenic transmission is urgently required.

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