L A Hyde
Affiliation: Schering-Plough Research Institute
- Studies to investigate the in vivo therapeutic window of the gamma-secretase inhibitor N2-[(2S)-2-(3,5-difluorophenyl)-2-hydroxyethanoyl]-N1-[(7S)-5-methyl-6-oxo-6,7-dihydro-5H-dibenzo[b,d]azepin-7-yl]-L-alaninamide (LY411,575) in the CRND8 mouseLynn A Hyde
Department of Neurobiology, Schering Plough Research Institute, Kenilworth, New Jersey 07033, USA
J Pharmacol Exp Ther 319:1133-43. 2006....
- Age-related deficits in context discrimination learning in Ts65Dn mice that model Down syndrome and Alzheimer's diseaseL A Hyde
Department of Pediatrics, University of Colorado School of Medicine, USA
Behav Neurosci 115:1239-46. 2001..Therefore, Ts65Dn mice have an age-related learning impairment that coincides with their age-related neuroanatomical abnormalities and, consequently, may be a useful model of AD...
- Age-progressing cognitive impairments and neuropathology in transgenic CRND8 miceLynn A Hyde
Schering Plough Research Institute, NJ 07033, Kenilworth, USA
Behav Brain Res 160:344-55. 2005..Therefore compared to their Non-Tg littermates, Tg CRND8 mice demonstrate cognitive impairments that progressed with age and seemed to coincide with the onset of beta-amyloid plaque deposition...
- Reactivity to object and spatial novelty is normal in older Ts65Dn mice that model Down syndrome and Alzheimer's diseaseLynn A Hyde
Department of Pediatrics, University of Colorado School of Medicine, Denver, CO 80262, USA
Brain Res 945:26-30. 2002..One may be related to recent studies that suggest that only rats with neonatal, but not adult, basal forebrain cholinergic 192 IgG-saporin lesions are impaired in reacting to spatial novelty...
- Discovery of gamma-secretase inhibitors efficacious in a transgenic animal model of Alzheimer's diseaseTheodros Asberom
Department of Chemical Research, Schering Plough Research Institute, 2015 Galloping Hill Road, Kenilworth, NJ 07033, USA
Bioorg Med Chem Lett 17:511-6. 2007..Strategies for subsequent improvement of the in vivo pharmacokinetic profile of the series are discussed. Resulting compounds significantly reduce Abeta levels in TgCRND8 mice after a single PO dosing at 30 mpk...
- Ts65Dn mice, a model for Down syndrome, have deficits in context discrimination learning suggesting impaired hippocampal functionL A Hyde
Department of Pediatrics, University of Colorado, School of Medicine, 4200 East Ninth Avenue Box C233, Denver, CO 80262, USA
Behav Brain Res 118:53-60. 2001..Therefore, Ts65Dn mice have learning deficits in a hippocampal dependent task that may be related to the loss of cholinergic input to the hippocampus, which occurs after 6 months of age...
- Increased auditory startle response and reduced prepulse inhibition of startle in transgenic mice expressing a double mutant form of amyloid precursor proteinMartha F McCool
CNS Biological Research, Schering Plough Research Institute, K15 2 2600, 2015 Galloping Hill Road, Kenilworth, NJ 07033, USA
Brain Res 994:99-106. 2003..These PPI deficits were present at pre- and post-plaque time points and did not appear to intensify with age; thus, they do not seem to correlate with the known neuropathology of TgCRND8 mice...
- Characterization of the nociceptin receptor (ORL-1) agonist, Ro64-6198, in tests of anxiety across multiple speciesG B Varty
Department of Neurobiology, K 15 2600, Schering Plough Research Institute, 2015 Galloping Hill Road, Kenilworth, NJ 07033, USA
Psychopharmacology (Berl) 182:132-43. 2005..Previous studies have demonstrated behaviors indicative of anxiolysis in rats pretreated with the nociceptin receptor (opioid receptor like-1, ORL-1) agonist, Ro64-6198...
- Increased seizure threshold and severity in young transgenic CRND8 miceRobert A Del Vecchio
CNS Biological Research, K 15 2600, Schering Plough Research Institute, 2015 Galloping Hill Road, Kenilworth, NJ 07033, USA
Neurosci Lett 367:164-7. 2004..Thus, the TgCRND8 mice are not only a model for Abeta production and plaque deposition, but may also be useful for AD associated seizure...
- Automated evaluation of sensitivity to foot shock in mice: inbred strain differences and pharmacological validationTatiana M Kazdoba
Department of Neurobiology, Schering Plough Research Institute, Kenilworth, NJ 07033, USA
Behav Pharmacol 18:89-102. 2007..Overall, these results demonstrate that our automated method is a quick and simple way to accurately assess potential foot shock sensitivity differences owing to strain, genotype or drug treatments...
- Small conformationally restricted piperidine N-arylsulfonamides as orally active gamma-secretase inhibitorsHubert Josien
Department of Chemical Research, Schering Plough Research Institute, 2015 Galloping Hill Road, Kenilworth, NJ 07302, USA
Bioorg Med Chem Lett 17:5330-5. 2007..Compounds active orally in lowering Abeta levels in Tg CRND8 mice were identified as potential treatments for Alzheimer's disease...
- Discovery of amide and heteroaryl isosteres as carbamate replacements in a series of orally active gamma-secretase inhibitorsMark D McBriar
Schering Plough Research Institute, 2015 Galloping Hill Road, Kenilworth, NJ 07033, USA
Bioorg Med Chem Lett 18:215-9. 2008..In several cases, amides lessened CYP liabilities in this class of gamma-secretase inhibitors. Selected compounds showed significant reduction of Abeta levels upon oral dosing in a transgenic murine model of Alzheimer's disease...
- Novel orally active morpholine N-arylsulfonamides gamma-secretase inhibitors with low CYP 3A4 liabilityHubert Josien
Department of CV and CNS Medicinal Chemistry, Schering Plough Research Institute, 2015 Galloping Hill Road, Kenilworth, NJ 07033, USA
Bioorg Med Chem Lett 19:6032-7. 2009..This resulted in compounds with improved CYP 3A4 profiles. Several analogs that were active at lowering Abeta levels in Tg CRND8 mice upon oral administration were identified...
- Motor learning in Ts65Dn mice, a model for Down syndromeL A Hyde
Departments of Pediatrics and Psychiatry, University of Colorado, School of Medicine, 4200 East Ninth Street, Denver, CO 80262, USA
Dev Psychobiol 38:33-45. 2001..These data indicate that Ts65Dn mice are not impaired in motor learning...
- Transgenic overexpression of neuromedin U promotes leanness and hypophagia in miceT J Kowalski
Department of CV Metabolic Diseases, Schering Plough Research Institute, Kenilworth, New Jersey 07033, USA
J Endocrinol 185:151-64. 2005..Despite the increased weight gain with high-fat feeding, glucose tolerance was significantly improved in the transgenic mice. These findings support the hypothesized role of NmU as an endogenous anorexigenic peptide...
- Estrogen restores cognition and cholinergic phenotype in an animal model of Down syndromeAnn Charlotte E Granholm
Department of Physiology and Neuroscience, Medical University of South Carolina, Charleston, SC 29425, USA
Physiol Behav 77:371-85. 2002..The findings also indicate that estrogen may act, at least partially, via endogenous growth factors. Collectively, the data suggest that ERT may be a viable therapeutic approach for women with DS coupled with dementia...
- Differential learning strategies in spatial and nonspatial versions of the Morris water maze in the C57BL/6J inbred mouse strainAmy Jo Stavnezer
Biobehavioral Sciences Graduate Degree Program, U 154, University of Connecticut, 3107 Horsebarn Hill Road, Storrs 06269 4154, USA
Behav Brain Res 133:261-70. 2002..Overall, C57 mice can learn both the spatial and nonspatial versions of the Morris maze presented here; however, the nonspatial version is more difficult and is solved using an egocentric strategy...
- Spatial and nonspatial Morris maze learning: impaired behavioral flexibility in mice with ectopias located in the prefrontal cortexLynn A Hyde
Biobehavioral Sciences Graduate Degree Program, University of Connecticut, U 154, 3107 Horsebarn Hill Road, Storrs 06269 4154, USA
Behav Brain Res 133:247-59. 2002..Thus, the presence of one or more ectopias in the prefrontal region of cortex disrupted one of the normal functions of the prefrontal cortex...