Aging is associated with increased incidence and/or severity of neurodegenerative pathologies. Oxygen‐mediated events are being considered as possible mechanisms responsible for the increasing neuronal vulnerability. Lipoxygenases are enzymes that, as cyclooxygenases (COX), can insert oxygen into the molecule of arachidonic acid and thereby synthesize inflammatory eicosanoids: leukotrienes [due to 5‐lipoxygenase (5‐LOX) activity] and prostaglandins (via COX activity). It appears that 5‐LOX is expressed in central nervous system neurons and may participate in neurodegeneration. 5‐LOX‐triggered cell death may be initiated by the enzymatic activity of 5‐LOX but could also occur via the nonenzymatic actions of the 5‐LOX protein; new data point to the possibility that 5‐LOX protein exerts actions such as interaction with tyrosine kinase receptors, cytoskeletal proteins, and the nucleus. The expression of neuronal 5‐LOX is susceptible to hormonal regulation, presumably due to the presence of hormone‐responsive elements in the structure of the 5‐LOX gene promoter. The expression of the 5‐LOX gene and the activity of the 5‐LOX pathway are increased in elderly subjects. One possible mechanism of such 5‐LOX up‐regulation implies the contribution of aging‐associated hormonal changes: relative melatonin deficiency and/or hyper‐glucocorticoidemia. Thus, the 5‐LOX pathway could become a promising target of neuroprotective therapies for the aging brain.—Manev, H., Uz, T., Sugaya, K., Qu, T. Putative role of neuronal 5‐lipoxygenase in an aging brain. FASEB J. 14, 1464–1469 (2000)
Human neuroblastoma cells, SH-SY5Y, are often used as a neuronal model to study Parkinson’s disease and dopamine release in the substantia nigra, a midbrain region that plays an important role in motor control. Using amperometric single-cell recordings of single vesicle release events, we can study molecular manipulations of dopamine release and gain a better understanding of the mechanisms of neurological diseases. However, single-cell analysis of neurotransmitter release using traditional techniques yields results with very low throughput. In this paper, we will discuss a monolithically-integrated CMOS sensor array that has the low-noise performance, fine temporal resolution, and 1024 parallel channels to observe dopamine release from many single cells with single-vesicle resolution. The measured noise levels of our transimpedance amplifier are 415, 622, and 1083 fARMS , at sampling rates of 10, 20, and 30 kS/s, respectively, without additional filtering. Post-CMOS processing is used to monolithically integrate 1024 on-chip gold electrodes, with an individual electrode size of 15 μm × 15 μm, directly on 1024 transimpedance amplifiers in the CMOS device. SU-8 traps are fabricated on individual electrodes to allow single cells to be interrogated and to reject multicellular clumps. Dopamine secretions from 76 cells are simultaneously recorded by loading the CMOS device with SH-SY5Y cells. In the 42-second measurement, a total of 7147 single vesicle release events are monitored. The study shows the CMOS device’s capability of recording vesicle secretion at a single-cell level, with 1024 parallel channels, to provide detailed information on the dynamics of dopamine release at a single-vesicle resolution.
ABSTRACT-The nucleus basalis magnocellularis (nbm)-lesioned rat is considered to be a model of the cholinergic dysfunction observed in the cerebral cortices of Alzheimer's disease patients. The cholin ergic markers, acetylcholine release and choline acetyltransferase activity, were decreased in the cerebral cortex of the nbm-lesioned rat. Kangenkaryu (KAN), a Chinese traditional medicine, is a typical prescription for the treatment of symptoms related to blood circulation deficiency. Orally ad ministered KAN following the nbm lesion significantly preserved the cholinergic markers. The present results indicate that KAN may preserve the activity of cholinergic neurons in the cerebral cortex after the nbm lesion.
Reelin is expressed during normal retinogenesis. This study shows that reelin is also upregulated following injury to the retina and cornea. The expression of reelin following injury suggests that reelin may play an important role in regulating stem cell trafficking in neuronal and nonneuronal tissues following injury similar to its role in normal organogenesis.
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