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Bigger brain oxygen reserves?
News & Comment
available methods of PrPSc detection are limited by the low amounts of abnormal protein. Therefore, this new method could lead to a diagnostic test for the presence of prions in tissue and biological fluids. CJ
Protein aggregates inhibit their own breakdown Cellular aggregates of abnormal proteins are common to many neurodegenerative diseases, including Alzheimer’s, Parkinson’s and Huntington’s diseases. A May 25 Science article now indicates that the aggregates accumulate partly because the functioning of the ubiquitin-proteosome system (UPS) that breaks down abnormal proteins is also compromised. Using mutant huntingtin and cystic fibrosis proteins in conjunction with GFP constructs to measure UPS function, researchers at Stanford University found that aggregates of these defective proteins inhibit the UPS, which exacerbates the problem by resulting in even more aggregates that further impair the proteosome. Disruption of the UPS probably also effects the regulation of apoptotic and cell death mechanisms. LO
Neural mechanisms in cocaine addictions and relapses
until they gave up pressing the drug injection lever. These previously-addicted animals resumed their lever-pressing frantically and continuously, however, after stimulation of the ventral subiculum of the hippocampus, but not the VTA. This mechanism might underlie the ability of contextual memories to trigger powerful drug cravings in former abusers. LO
Photoreceptor action potentials
Light-induced biochemical processes in mammalian photoreceptors cause graded hyperpolarization of these neurons, which are commonly thought to be non-spiking. Researchers from Fujita Health University in Japan, however, have studied these cells electrophysiologically in surgically excised retina and found that human rod photoreceptors do fire sodium-ion action potentials in response to injection of depolarizing currents. Additionally, spikes were observed at the termination of light stimuli, which amplifies an ‘off’ response by resulting in more neurotransmitter release. The full paper appears in the May issue of Neuron. LO
A single injection of cocaine can induce long-term potentiation in dopaminergic neurons in the ventral tegmental area (VTA) of mice, California researchers report in the May 31 issue of Nature. Thus, NMDA receptor-dependent sensitization in this ‘reward’ brain area might contribute to the early stages of drug addiction. In a separate, May 11 Science paper, Albert Einstein College of Medicine scientists show that neural pathways underlying cocaine addiction and cocaine craving are different. Rats became addicted to cocaine by selfadministration and then were withdrawn http://tins.trends.com
TRENDS in Neurosciences Vol.24 No.8 August 2001
Bigger brain oxygen reserves? A June 5 Proc. Natl. Acad. Sci. U. S. A. paper from researchers at Washington University in St Louis calls into question the use of imaging techniques that measure blood flow as a marker of brain activity. PET scans of healthy individuals indicate that baseline cerebral blood flow does not increase to compensate when individuals are in low oxygen (hypoxic) environments, nor are normal increases in blood flow during visual activity larger in hypoxic
443
atmospheres. These data suggest that cerebral blood flow and cerebral oxygen metabolic rate are not as tightly coupled as previously assumed. The authors offer an alternative mathematical model of determining brain activity that avoids conjecture as to basal level of brain oxygen and allows that more oxygen is delivered than is utilized. Oxygen-independent mechanisms that drive cerebral blood flow are as yet unknown. LO
Structure and function in ACh synapses An electrophysiological observation by neurobiologists from the Netherlands that glia cells decrease neuronal responses to acetylcholine (ACh) led to their recent discovery and crystal structure of a snail acetylcholine binding protein. In a novel mechanism of synaptic modulation, presynaptically-released ACh stimulates the vesicular release of the binding protein from glia cells into the synaptic cleft, where it buffers ACh away from postsynaptic receptors. Additionally, the protein structure of this novel protein reveals important details of the ligandbinding domain of the nicotinic ACh receptor that will aid in drug-design efforts. Two papers appear in the May 17 issue of Nature. LO
Scientists file stem cell suit
Several stem cell scientists, together with actor and spinal-cord injury victim Christopher Reeve, Parkinson’s activist and suffer James Cordy, and business executive and diabetes patient Jame Tyree, have filed suits against the US Department of Health and Human Services and the NIH. The complaint asks the US District Court in D.C. to accept NIH guidelines for stem cell research and encourages the NIH to fund research on cells derived from human embryos or fetal tissue. The US government is required to reply by the middle of July. LO
0166-2236/01/$ – see front matter © 2001 Elsevier Science Ltd. All rights reserved.
available methods of PrPSc detection are limited by the low amounts of abnormal protein. Therefore, this new method could lead to a diagnostic test for the presence of prions in tissue and biological fluids. CJ
Protein aggregates inhibit their own breakdown Cellular aggregates of abnormal proteins are common to many neurodegenerative diseases, including Alzheimer’s, Parkinson’s and Huntington’s diseases. A May 25 Science article now indicates that the aggregates accumulate partly because the functioning of the ubiquitin-proteosome system (UPS) that breaks down abnormal proteins is also compromised. Using mutant huntingtin and cystic fibrosis proteins in conjunction with GFP constructs to measure UPS function, researchers at Stanford University found that aggregates of these defective proteins inhibit the UPS, which exacerbates the problem by resulting in even more aggregates that further impair the proteosome. Disruption of the UPS probably also effects the regulation of apoptotic and cell death mechanisms. LO
Neural mechanisms in cocaine addictions and relapses
until they gave up pressing the drug injection lever. These previously-addicted animals resumed their lever-pressing frantically and continuously, however, after stimulation of the ventral subiculum of the hippocampus, but not the VTA. This mechanism might underlie the ability of contextual memories to trigger powerful drug cravings in former abusers. LO
Photoreceptor action potentials
Light-induced biochemical processes in mammalian photoreceptors cause graded hyperpolarization of these neurons, which are commonly thought to be non-spiking. Researchers from Fujita Health University in Japan, however, have studied these cells electrophysiologically in surgically excised retina and found that human rod photoreceptors do fire sodium-ion action potentials in response to injection of depolarizing currents. Additionally, spikes were observed at the termination of light stimuli, which amplifies an ‘off’ response by resulting in more neurotransmitter release. The full paper appears in the May issue of Neuron. LO
A single injection of cocaine can induce long-term potentiation in dopaminergic neurons in the ventral tegmental area (VTA) of mice, California researchers report in the May 31 issue of Nature. Thus, NMDA receptor-dependent sensitization in this ‘reward’ brain area might contribute to the early stages of drug addiction. In a separate, May 11 Science paper, Albert Einstein College of Medicine scientists show that neural pathways underlying cocaine addiction and cocaine craving are different. Rats became addicted to cocaine by selfadministration and then were withdrawn http://tins.trends.com
TRENDS in Neurosciences Vol.24 No.8 August 2001
Bigger brain oxygen reserves? A June 5 Proc. Natl. Acad. Sci. U. S. A. paper from researchers at Washington University in St Louis calls into question the use of imaging techniques that measure blood flow as a marker of brain activity. PET scans of healthy individuals indicate that baseline cerebral blood flow does not increase to compensate when individuals are in low oxygen (hypoxic) environments, nor are normal increases in blood flow during visual activity larger in hypoxic
443
atmospheres. These data suggest that cerebral blood flow and cerebral oxygen metabolic rate are not as tightly coupled as previously assumed. The authors offer an alternative mathematical model of determining brain activity that avoids conjecture as to basal level of brain oxygen and allows that more oxygen is delivered than is utilized. Oxygen-independent mechanisms that drive cerebral blood flow are as yet unknown. LO
Structure and function in ACh synapses An electrophysiological observation by neurobiologists from the Netherlands that glia cells decrease neuronal responses to acetylcholine (ACh) led to their recent discovery and crystal structure of a snail acetylcholine binding protein. In a novel mechanism of synaptic modulation, presynaptically-released ACh stimulates the vesicular release of the binding protein from glia cells into the synaptic cleft, where it buffers ACh away from postsynaptic receptors. Additionally, the protein structure of this novel protein reveals important details of the ligandbinding domain of the nicotinic ACh receptor that will aid in drug-design efforts. Two papers appear in the May 17 issue of Nature. LO
Scientists file stem cell suit
Several stem cell scientists, together with actor and spinal-cord injury victim Christopher Reeve, Parkinson’s activist and suffer James Cordy, and business executive and diabetes patient Jame Tyree, have filed suits against the US Department of Health and Human Services and the NIH. The complaint asks the US District Court in D.C. to accept NIH guidelines for stem cell research and encourages the NIH to fund research on cells derived from human embryos or fetal tissue. The US government is required to reply by the middle of July. LO
0166-2236/01/$ – see front matter © 2001 Elsevier Science Ltd. All rights reserved.