ELIZA

return kwic search for system out of >500 occurrences
331253 occurrences (No.58 in the rank) during 5 years in the PubMed. [no cache] 500 found

305) Its function in the central nervous system (CNS) remains unknown.

--- ABSTRACT ---

PMID:24468826 DOI:10.1038/mp.2013.192

2015 Molecular psychiatry

* FGF-21, a novel metabolic regulator, has a robust neuroprotective role and is markedly elevated in neurons by mood stabilizers.

- Fibroblast growth factor-21 (FGF-21) is a new member of the FGF super-family and an important endogenous regulator of glucose and lipid metabolism. It has been proposed as a therapeutic target for diabetes and obesity. Its function in the central nervous system (CNS) remains unknown. Previous studies from our laboratory demonstrated that aging primary neurons are more vulnerable to glutamate-induced excitotoxicity, and that co-treatment with the mood stabilizers lithium and valproic acid (VPA) induces synergistic neuroprotective effects. This study sought to identify molecule(s) involved in these synergistic effects. We found that FGF-21 mRNA was selectively and markedly elevated by co-treatment with lithium and VPA in primary rat brain neurons. FGF-21 protein levels were also robustly increased in neuronal lysates and culture medium following lithium-VPA co-treatment. Combining glycogen synthase kinase-3 (GSK-3) inhibitors with VPA or histone deacetylase (HDAC) inhibitors with lithium synergistically increased FGF-21 mRNA levels, supporting that synergistic effects of lithium and VPA are mediated via GSK-3 and HDAC inhibition, respectively. Exogenous FGF-21 protein completely protected aging neurons from glutamate challenge. This neuroprotection was associated with enhanced Akt-1 activation and GSK-3 inhibition. Lithium-VPA co-treatment markedly prolonged lithium-induced Akt-1 activation and augmented GSK-3 inhibition. Akt-1 knockdown markedly decreased FGF-21 mRNA levels and reduced the neuroprotection induced by FGF-21 or lithium-VPA co-treatment. In addition, FGF-21 knockdown reduced lithium-VPA co-treatment-induced Akt-1 activation and neuroprotection against excitotoxicity. Together, our novel results suggest that FGF-21 is a key mediator of the effects of these mood stabilizers and a potential new therapeutic target for CNS disorders.

--- ABSTRACT END ---

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[frequency of next (right) word to system]

(1)88 null	(12)6 by	(23)3 (ANS)	(34)2 diseases
(2)30 and	(13)6 has	(24)3 (CNS)	(35)2 including
(3)19 is	(14)5 are	(25)3 a	(36)2 involvement
(4)18 of	(15)5 might	(26)3 after	(37)2 known
(5)18 was	(16)5 the	(27)3 as	(38)2 on
(6)17 in	(17)4 Adhesive	(28)3 based	(39)2 one
(7)16 that	(18)4 can	(29)3 development	(40)2 plays
(8)15 for	(19)4 have	(30)3 we	(41)2 related
(9)13 to	(20)4 may	(31)2 (GIS)	(42)2 results
(10)8 which	(21)4 using	(32)2 containing	(43)2 used
(11)7 with	(22)4 were	(33)2 demonstrated

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--- WordNet output for system --- =>制度組織体系的方式, システム, 組織, 整然とした手順, (思想などの)体系, 体制 Overview of noun system The noun system has 9 senses (first 8 from tagged texts) 1. (43) system -- (instrumentality that combines interrelated interacting artifacts designed to work as a coherent entity; "he bought a new stereo system"; "the system consists of a motor and a small computer") 2. (23) system, scheme -- (a group of independent but interrelated elements comprising a unified whole; "a vast system of production and distribution and consumption keep the country going") 3. (14) system -- ((physical chemistry) a sample of matter in which substances in different phases are in equilibrium; "in a static system oil cannot be replaced by water on a surface"; "a system generating hydrogen peroxide") 4. (10) system, system of rules -- (a complex of methods or rules governing behavior; "they have to operate under a system they oppose"; "that language has a complex system for indicating gender") 5. (8) arrangement, organization, organisation, system -- (an organized structure for arranging or classifying; "he changed the arrangement of the topics"; "the facts were familiar but it was in the organization of them that he was original"; "he tried to understand their system of classification") 6. (7) system -- (a group of physiologically or anatomically related organs or parts; "the body has a system of organs for digestion") 7. (6) system -- (a procedure or process for obtaining an objective; "they had to devise a system that did not depend on cooperation") 8. (1) system -- (the living body considered as made up of interdependent components forming a unified whole; "exercise helped him get the alcohol out of his system") 9. organization, organisation, system -- (an ordered manner; orderliness by virtue of being methodical and well organized; "his compulsive organization was not an endearing quality"; "we can't do it unless we establish some system around here") --- WordNet end ---