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Senescence-accelerated mouse (SAMP8) is known as a murine model of accelerated aging and memory dysfunction. The binding activity of [3H] 1-(2-chlorophenyl)-N-methyl-N-(1-methylpropyl)-3-isoquinolinecarboxam ide (PK-11195) as a neurochemical marker of gliosis markedly increased with aging in the cerebral cortex and hippocampus of SAMP8. Immunoreactivity for(More)
Stress proteins located in the cytosol or endoplasmic reticulum (ER) maintain cell homeostasis and afford tolerance to severe insults. In neurodegenerative diseases, several chaperones ameliorate the accumulation of misfolded proteins triggered by oxidative or nitrosative stress, or of mutated gene products. Although severe ER stress can induce apoptosis,(More)
Endoplasmic reticulum-associated degradation (ERAD) is a system by which proteins accumulated in the endoplasmic reticulum (ER) are retrotranslocated to the cytosol and degraded by the ubiquitin-proteasome pathway. HRD1 is expressed in brain neurons and acts as an ERAD ubiquitin ligase. Amyloid precursor protein (APP) is processed into amyloid-beta peptides(More)
The senescence accelerated mouse (SAM) is known as a murine model of aging. SAM consists of senescence accelerated-prone mouse (SAMP) and senescence accelerated-resistant mouse (SAMR). Previous studies reported that SAMP10 exhibits age-related learning impairments and behavioral depression in a tail suspension test after 7 months. We investigated the(More)
To clarify the quantitative and qualitative changes in type IV phosphodiesterase (PDE IV) with aging, phosphodiesterase (PDE) activity and [3H]rolipram binding in the cytosolic fraction from the brains of young and aged rats were examined. In all areas of the aged (100-week-old) rat brain except for hippocampus, the PDE activity was decreased by about half(More)
To clarify the role of cholinergic neurons in the amygdala on learning and memory, scopolamine was injected topically into the bilateral amygdala of mice, and the ability to perform two types of passive avoidance tasks (step-through and step-down) was investigated. On the first day mice performed the learning trial and on the second day their retention was(More)
Leptin is known to be an important circulating signal for regulation of food intake and body weight. These effects were suggested to be mediated through the hypothalamic center via the Ob-Rb receptor (long isoform of leptin receptor). Although short isoforms of leptin receptor exist in many regions of the brain, there has been little in vivo functional(More)
High K+ and N-methyl-D-aspartate (NMDA) evoked L-[3H]noradrenaline (NA) release to a similar degree in the brain slices of 1-month-old senescence-accelerated resistant mice (SAM-R/1) and senescence-accelerated prone mice (SAM-P/8). However, 30 mM KCl-induced L-[3H]NA release significantly diminished in SAM-P/8 from 3 to 12 months without changing in(More)
Leptin is a circulating molecule for the regulation of food intake and body weight suggested to be mediated in the hypothalamus via Ob-Rb receptor, which activates Janus kinase-signal transducer and activator of transcription (STAT) pathways. Although leptin receptors exist in many regions of the brain, there have been few in vivo functional studies of(More)
In the present study, we investigated regulatory mechanisms of bacterial endotoxin-induced STAT3 activation in the brain. Intraperitoneal injection of lipopolysaccharide (LPS) dose-dependently (0.5-5000 microg/kg) induced STAT3 phosphorylation in the hypothalamus. LPS-induced STAT3 phosphorylation was peaked at 2-4 h and declined there after. Moreover,(More)