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The amyloid-beta precursor protein (APP) is directly and efficiently cleaved by caspases during apoptosis, resulting in elevated amyloid-beta (A beta) peptide formation. The predominant site of caspase-mediated proteolysis is within the cytoplasmic tail of APP, and cleavage at this site occurs in hippocampal neurons in vivo following acute excitotoxic or(More)
A dysregulated hypothalamic-pituitary-adrenal axis (HPA) has been implicated in major depressive disorder and most commonly used animal models of depression have been shown to elevate circulating levels of plasma corticosterone. We have compared the effects of chronic and acute corticosterone administration on hippocampal cell proliferation (as measured by(More)
This study examined the effects of acute administration of delta-9-tetrahydrocannabinol (delta 9-THC), the psychoactive ingredient in marijuana, on extracellular efflux of dopamine (DA) and its metabolites as measured by in vivo microdialysis in nucleus accumbens of conscious, freely-moving rats. delta 9-THC, at low doses (0.5-1.0 mg/kg), which(More)
The association between genetic marker alleles was estimated for two regions of the bovine genome from a random sample of 50 young dairy bulls born in the United Kingdom between 1988 and 1995. Microsatellite marker genotypes were obtained for six markers on chromosome 2 and seven markers on chromosome 6, spanning 38 and 20 cM, respectively. Two different(More)
The localization of substance P in brain regions that coordinate stress responses and receive convergent monoaminergic innervation suggested that substance P antagonists might have psychotherapeutic properties. Like clinically used antidepressant and anxiolytic drugs, substance P antagonists suppressed isolation-induced vocalizations in guinea pigs. In a(More)
In several pedigrees of early onset familial Alzheimer's disease (FAD), point mutations in the beta-amyloid precursor protein (APP) gene are genetically linked to the disease. This finding implicates APP in the pathogenesis of Alzheimer's disease in these individuals. To understand the in vivo function of APP and its processing, we have generated an(More)
The present experiment explored whether delta 9-tetrahydrocannabinol (delta 9-THC), the psychoactive ingredient in marijuana, shares with other drugs of abuse the ability to facilitate brain stimulation reward acutely, as measured by electrical intracranial self-stimulation (ICSS). Laboratory rats were implanted with stimulation electrodes in the medial(More)
Mutations in the beta-amyloid precursor protein are strongly associated with some cases of familial Alzheimer's disease. The normal physiological role of beta-amyloid precursor protein in the brain was evaluated in a cross-sectional analysis of mice deficient in beta-amyloid precursor protein. Compared with wild-type control mice the beta-amyloid precursor(More)
1 same time, neurons undergoing apoptosis generate ele-exacerbation of a vicious cycle which culminates in the and Molecular Biology progressive neuronal loss that is the hallmark of Alzhei-Neurosciences Research Centre mer's disease. For this hypothesis to be true, compo-Merck Sharp and Dohme Research Laboratories nents of the apoptotic machinery must(More)
OBJECTIVES To examine the relative risks of additional educational needs (AENs) in children exposed to antiepileptic drug (AED) monotherapy and polytherapy regimes in utero. METHODS A retrospective survey of women between the ages of 16 to 40 registered at the Mersey Regional Epilepsy Clinic, who received a postal questionnaire concerning their experience(More)