ELIZA

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367) DG-specific deficits are accompanied by a significant reduction in NMDAR GluN1, GluN2A, and GluN2B subunit levels and reduced serine 831 GluA1 phosphorylation specifically in this region.

--- ABSTRACT ---

PMID:23968838 DOI:10.1093/cercor/bht237

2015 Cerebral cortex (New York, N.Y. : 1991)

* Rescue of NMDAR-dependent synaptic plasticity in Fmr1 knock-out mice.

- Fragile X Syndrome (FXS) is the most common form of inherited intellectual disability and results from a loss of Fragile X mental retardation protein (FMRP). FMRP is important for mRNA shuttling and translational control and binds to proteins important for synaptic plasticity. Like many developmental disorders, FXS is associated with alterations in synaptic plasticity that may impair learning and memory processes in the brain. However, it remains unclear whether FMRP plays a ubiquitous role in synaptic plasticity in all brain regions. We report that a loss of FMRP leads to impairments in N-methyl-D-aspartate receptor (NMDAR)-dependent synaptic plasticity in the dentate gyrus (DG), but not in the cornu ammonis area 1 (CA1) subregion of the hippocampus of adult mice. DG-specific deficits are accompanied by a significant reduction in NMDAR GluN1, GluN2A, and GluN2B subunit levels and reduced serine 831 GluA1 phosphorylation specifically in this region. Importantly, we demonstrate that treatment with NMDAR co-agonists (glycine or D-serine) independently rescue impairments in NMDAR-dependent synaptic plasticity in the DG of the Fragile X mental retardation 1 (Fmr1) knockout mouse. These findings implicate the NMDAR in the pathophysiology of FXS and suggest that indirect agonists of the NMDAR may be a successful therapeutic intervention in FXS.

--- ABSTRACT END ---

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(1)236 of	(8)5 at	(15)3 using	(22)2 especially
(2)40 null	(9)4 are	(16)3 while	(23)2 induced
(3)38 in	(10)4 by	(17)2 after	(24)2 or
(4)35 were	(11)4 may	(18)2 between	(25)2 to
(5)34 and	(12)4 on	(19)2 compared
(6)6 was	(13)3 did	(20)2 decreased
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--- WordNet output for levels --- Overview of noun level The noun level has 8 senses (first 6 from tagged texts) 1. (69) degree, grade, level -- (a position on a scale of intensity or amount or quality; "a moderate grade of intelligence"; "a high level of care is required"; "it is all a matter of degree") 2. (22) grade, level, tier -- (a relative position or degree of value in a graded group; "lumber of the highest grade") 3. (15) degree, level, stage, point -- (a specific identifiable position in a continuum or series or especially in a process; "a remarkable degree of frankness"; "at what stage are the social sciences?") 4. (5) level -- (height above ground; "the water reached ankle level"; "the pictures were at the same level") 5. (1) level, spirit level -- (indicator that establishes the horizontal when a bubble is centered in a tube of liquid) 6. (1) horizontal surface, level -- (a flat surface at right angles to a plumb line; "park the car on the level") 7. level, layer, stratum -- (an abstract place usually conceived as having depth; "a good actor communicates on several levels"; "a simile has at least two layers of meaning"; "the mind functions on many strata simultaneously") 8. floor, level, storey, story -- (a structure consisting of a room or set of rooms at a single position along a vertical scale; "what level is the office on?") Overview of verb level The verb level has 6 senses (first 3 from tagged texts) 1. (4) level -- (aim at; "level criticism or charges at somebody") 2. (1) level, raze, rase, dismantle, tear down, take down, pull down -- (tear down so as to make flat with the ground; "The building was levelled") 3. (1) flush, level, even out, even -- (make level or straight; "level the ground") 4. charge, level, point -- (direct into a position for use; "point a gun"; "He charged his weapon at me") 5. level -- (talk frankly with; lay it on the line; "I have to level with you") 6. level, level off -- (become level or even; "The ground levelled off") --- WordNet end ---