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Yin-Guo Lin
Cephalon
11Publications
9H-index
664Citations
Publications 11
Newest
#2Yin-Guo LinH-Index: 9
Last.Robert SimanH-Index: 26
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It has been challenging to develop transgenic and gene-targeted mouse models that recapitulate all of the neuropathological features of Alzheimer’s disease (AD). For example, in the APP/PS-1 double knock-in mutant mouse (DKI), frank neurodegeneration is not observed at middle age and synapse loss is pronounced only within amyloid plaques. Here, we investigated whether continued amyloid deposition and advanced age of 24–27 months lead to loss of neurons and synapses, tau hyperphosphorylation, and...
10 Citations
#1Robert L. Hudkins (Cephalon)H-Index: 21
#2Lisa D. Aimone (Cephalon)H-Index: 19
Last.Edward R. Bacon (Cephalon)H-Index: 11
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Abstract H3R structure–activity relationships on a novel class of pyridazin-3-one H3R antagonists/inverse agonists are disclosed. Modifications of the pyridazinone core, central phenyl ring and linker led to the identification of molecules with excellent target potency, selectivity and pharmacokinetic properties. Compounds 13 and 21 displayed potent functional H3R antagonism in vivo in the rat dipsogenia model and demonstrated robust wake activity in the rat EEG/EMG model.
19 CitationsSource
#1John A. Gruner (Cephalon)H-Index: 11
#2Val R. Marcy (Cephalon)H-Index: 6
Last.Maciej Gasior (Cephalon)H-Index: 7
view all 6 authors...
ALTHOUGH THE REGULATION OF SLEEP AND WAKE STATES IS BELIEVED TO INVOLVE BRAIN DOPAMINE (DA),1–3 ITS ROLE APPEARS COMPLEX. ACTIVATION of dopamine D1 receptors increases wake and reduces rapid eye movement sleep (REMS).4 The effects of activation of dopamine D2 receptors depend on dose and location.5 While D1 and D2 receptor agonists injected into intracerebral ventricles can increase wake,6 microinjection of mixed D1/D2 receptor agonists (e.g., apomorphine) into the ventral tegmental area increas...
28 CitationsSource
#1Dorothy G. Flood (Cephalon)H-Index: 37
#2Yin-Guo Lin (Cephalon)H-Index: 9
Last.David S. Howland (Cephalon)H-Index: 5
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Abstract Many transgenic mouse models of Alzheimer's disease (AD) that deposit amyloid (Aβ) have been produced, but development of an Aβ-depositing rat model has not been successful. Here, we describe a rat model with extracellular fibrillar Aβ deposition. Two lines of Sprague Dawley rats with transgenes expressing human amyloid precursor protein (APP) with the familial AD (FAD) mutations K670N/M671L and K670N/M671L/V717I were crossed. Aβ production in the double homozygous rats was sufficient f...
59 CitationsSource
#1Elaine M. Fiocchi (Cephalon)H-Index: 1
#2Yin-Guo Lin (Cephalon)H-Index: 9
Last.Dorothy G. Flood (Cephalon)H-Index: 37
view all 5 authors...
Abstract Modafinil increases waking and labeling of Fos, a marker of neuronal activation. In the present study, armodafinil, the R -enantiomer of racemic modafinil, was administered to rats at 30 or 100 mg/kg i.p. about 5 h after lights on (circadian time 5 and near the midpoint of the sleep phase of the sleep:wake cycle) to assess its effects on sleep/wake activity and Fos activation. Armodafinil at 100 mg/kg increased wakefulness for 2 h, while 30 mg/kg armodafinil only briefly increased wakef...
12 CitationsSource
#1Dorothy G. Flood (Cephalon)H-Index: 37
#2Andrew G. Reaume (Cephalon)H-Index: 17
Last.Richard W. Scott (Cephalon)H-Index: 39
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Abstract To investigate the consequences of mutant presenilin-1 (PS-1) expression under the control of the normal PS-1 gene, a gene-targeted mouse bearing the FAD mutation P264L was made. Gene-targeted models are distinct from transgenic models because the mutant gene is expressed at normal levels, in the absence of the wild-type protein. PS-1 P264L/P264L mice had normal expression of PS-1 mRNA, but levels of the N- and C-terminal protein fragments of PS-1 were reduced while levels of the holopr...
106 CitationsSource
#1Mary J. Savage (Cephalon)H-Index: 23
#2Yin-Guo Lin (Cephalon)H-Index: 9
Last.Richard W. Scott (Cephalon)H-Index: 39
view all 5 authors...
The mechanisms by which neurons and synapses are lost in Alzheimer's disease (AD) are not completely understood. To characterize potential signaling events linked to AD pathogenesis, activation-specific antibodies were used to examine mitogen-activated protein kinase (MAPK) kinase pathways at various ages in mice transgenic for human amyloid precursor protein-695 with the Swedish familial AD mutations (Tg2576) and homozygous for a P264L familial AD mutation introduced by targeting of the preseni...
219 CitationsSource
#1Robert Siman (UPenn: University of Pennsylvania)H-Index: 26
#2Andrew G. ReaumeH-Index: 17
Last.Dorothy G. FloodH-Index: 37
view all 7 authors...
The pathogenic mechanism linking presenilin-1 (PS-1) gene mutations to familial Alzheimer's disease (FAD) is uncertain, but has been proposed to include increased neuronal sensitivity to degeneration and enhanced amyloidogenic processing of the β-amyloid precursor protein (APP). We investigated this issue by using gene targeting with the Cre-lox system to introduce an FAD-linked P264L mutation into the endogenous mouse PS-1 gene, an approach that maintains normal regulatory controls over express...
120 CitationsSource
#1Dorothy G. FloodH-Index: 37
#2Mary J. SavageH-Index: 23
Last.Richard W. ScottH-Index: 39
view all 8 authors...
Source
#1Dorothy G. Flood (Cephalon)H-Index: 37
#2Andrew G. Reaume (Cephalon)H-Index: 17
Last.Richard W. Scott (Cephalon)H-Index: 39
view all 8 authors...
The role of oxidative damage in neurodegenerative disease was investigated in mice lacking cytoplasmic Cu/Zn superoxide dismutase (SOD), created by deletion of the SOD1 gene ( SOD1 /− ). SOD1 −/− mice developed a chronic peripheral hindlimb axonopathy. Mild denervation of muscle was detected at 2 months, and behavioral and physiological motor deficits were present at 5–7 months of age. Ventral root axons were shrunken but were normal in number. The somatosensory system in SOD1 −/− mice was mildl...
91 CitationsSource
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