0

Cardiovascular and Metabolic Disease Center
Mitochondrial Research Affinity Collaboration-Laboratories & Engineering

Home > 0

News Tips from The Journal of Neuroscience

  • 작성자한진
  • 작성일2006-04-21 19:57:28
  • 조회수3935
  • 첨부파일첨부파일
1. Pain Makes CaMKII Go Up and Down Max Larsson and Jonas Broman Aparticularly intense painful stimulus enhances the sensation evoked by subsequent noxious stimuli. This hyperalgesia may result from facilitation of sensory neurotransmission in the spinal cord, perhaps by mechanisms similar to synaptic plasticity in other pathways. In this week's Journal, Larsson and Broman used immunolabeling of calcium/calmodulin-dependent kinase II (CaMKII) to track the associated modulation of spinal cord pathways. The translocation of autophosphorylated CaMKII to the postsynaptic density makes it one marker of synaptic plasticity. The authors injected rat hindpaws with capsaicin to induce hyperalgesia. Transganglionic tracing of the capsaicin injection site marked the nonpeptidergic class of nociceptors, but not peptidergic nociceptive neurons that express substance P and calcitonin generelated peptide. Phosphorylated CaMKII more than doubled in dorsal horn synapses formed by peptidergic neurons and fell by about one-half in synapses formed by labeled, nonpeptidergic neurons. In low-threshold mechanoreceptor neurons, CaMKII expression did not change with capsaicin treatment. 2. D1, GAD, and Working Memory Nobuhide Kobori and Pramod K. Dash Kobori and Dash examined deficits in working memory after a mild concussive brain injury that did not cause overt neuronal loss. The authors targeted the medial prefrontal cortex (mPFC), known to be important for working memory (WM). Rats performed a delay match-to-place task, in which they escaped a water maze to a hidden platform (the location trial), were removed from the maze, and then relocated the platform (the match trial). Brain-injured rats displayed a random search pattern during the match trial indicative of impaired WM. The memory deficits were associated with neurochemical changes in mPFC, including higher levels of D1 dopamine receptors and more neurons detected by immunolabeling for GAD67, the GABA-synthesizing enzyme. GABA receptor antagonists improved WM, and remarkably a single dose of the D1 receptor antagonist SCH23390 [R(+)-7-chloro-8-hydroxy-3-methyl-1-phenyl-2,3,4,5-tetrahydro-1 H-3-benzazepine hydrochloride] reduced GAD67 expression and improved WM for several days. Pass the SCH23390, please. 3. Focusing Attention on the Thalamic Reticular Nucleus Kerry McAlonan, James Cavanaugh, and Robert H. Wurtz In this week's Journal, McAlonan et al. explore the "attentional searchlight" hypothesis for the thalamic reticular nucleus (TRN). The TRN consists of a thin layer of GABAergic neurons that receive excitatory inputs from the lateral geniculate nucleus (LGN) and cortex and send inhibitory output back to the LGN. The authors recorded spike rates of individual visual TRN neurons in monkeys. These neurons had a high basal firing rate, providing tonic inhibition to LGN, and short latency (∼25 ms) transient responses to visual stimuli. Because the TRN receives multimodal input, the authors examined responses in which monkeys shifted their attention from auditory to visual stimuli. Spiking of TRN neurons increased with the attentional shift, but latency and duration remained the same. The authors suggest that TRN neurons facilitate visual detection and discrimination by switching visual LGN neurons from tonic to burst firing, or by surround inhibition of nonvisual LGN neurons. 4. SOD1 Mutants in and out of Mitochondria Daniel Bergemalm, P. Andreas Jonsson, Karin S. Graffmo, Peter M. Andersen, Thomas Br?nstr?, Anna Rehnmark, and Stefan L. Marklund CuZn superoxide dismutase (SOD1)mutations underlie some cases of familial amyotrophic lateral sclerosis (ALS). Mutations cause a cytoxic gain-of-function of this antioxidant molecule that is expressed in the cytosol as well as the mitochondrial intramembrane space. Transgenic mice expressing high levels of stable human SOD1 (hSOD1) mutants become symptomatic, but the high expressed enzyme is Cu-deficient, and their intrasubunit disulfide bonds are reduced. This week, Bergemalm et al. show that these changes lead to nonphysiological mitochondrial loading of stable hSOD11 mutants, ∼100?fold higher than the endogenous mouse SOD1. In contrast, mice that expressed the unstable mutants G85R and G127X had 100- and 1000-fold lower mitochondrial hSOD1 levels, suggesting that unstable mutants do not cause disease by affecting mitochondria. The authors conclude that mitochondrial accumulation of SOD1 per se does not lead to motor neuron injury and that mitochondrial overloading may complicate interpretations of studies in mouse models expressing the stable mutants. 1. Pain Makes CaMKII Go Up and Down Max Larsson and Jonas Broman Aparticularly intense painful stimulus enhances the sensation evoked by subsequent noxious stimuli. This hyperalgesia may result from facilitation of sensory neurotransmission in the spinal cord, perhaps by mechanisms similar to synaptic plasticity in other pathways. In this week's Journal, Larsson and Broman used immunolabeling of calcium/calmodulin-dependent kinase II (CaMKII) to track the associated modulation of spinal cord pathways. The translocation of autophosphorylated CaMKII to the postsynaptic density makes it one marker of synaptic plasticity. The authors injected rat hindpaws with capsaicin to induce hyperalgesia. Transganglionic tracing of the capsaicin injection site marked the nonpeptidergic class of nociceptors, but not peptidergic nociceptive neurons that express substance P and calcitonin generelated peptide. Phosphorylated CaMKII more than doubled in dorsal horn synapses formed by peptidergic neurons and fell by about one-half in synapses formed by labeled, nonpeptidergic neurons. In low-threshold mechanoreceptor neurons, CaMKII expression did not change with capsaicin treatment. 2. D1, GAD, and Working Memory Nobuhide Kobori and Pramod K. Dash Kobori and Dash examined deficits in working memory after a mild concussive brain injury that did not cause overt neuronal loss. The authors targeted the medial prefrontal cortex (mPFC), known to be important for working memory (WM). Rats performed a delay match-to-place task, in which they escaped a water maze to a hidden platform (the location trial), were removed from the maze, and then relocated the platform (the match trial). Brain-injured rats displayed a random search pattern during the match trial indicative of impaired WM. The memory deficits were associated with neurochemical changes in mPFC, including higher levels of D1 dopamine receptors and more neurons detected by immunolabeling for GAD67, the GABA-synthesizing enzyme. GABA receptor antagonists improved WM, and remarkably a single dose of the D1 receptor antagonist SCH23390 [R(+)-7-chloro-8-hydroxy-3-methyl-1-phenyl-2,3,4,5-tetrahydro-1 H-3-benzazepine hydrochloride] reduced GAD67 expression and improved WM for several days. Pass the SCH23390, please. 3. Focusing Attention on the Thalamic Reticular Nucleus Kerry McAlonan, James Cavanaugh, and Robert H. Wurtz In this week's Journal, McAlonan et al. explore the "attentional searchlight" hypothesis for the thalamic reticular nucleus (TRN). The TRN consists of a thin layer of GABAergic neurons that receive excitatory inputs from the lateral geniculate nucleus (LGN) and cortex and send inhibitory output back to the LGN. The authors recorded spike rates of individual visual TRN neurons in monkeys. These neurons had a high basal firing rate, providing tonic inhibition to LGN, and short latency (∼25 ms) transient responses to visual stimuli. Because the TRN receives multimodal input, the authors examined responses in which monkeys shifted their attention from auditory to visual stimuli. Spiking of TRN neurons increased with the attentional shift, but latency and duration remained the same. The authors suggest that TRN neurons facilitate visual detection and discrimination by switching visual LGN neurons from tonic to burst firing, or by surround inhibition of nonvisual LGN neurons. 4. SOD1 Mutants in and out of Mitochondria Daniel Bergemalm, P. Andreas Jonsson, Karin S. Graffmo, Peter M. Andersen, Thomas Br?nstr?, Anna Rehnmark, and Stefan L. Marklund CuZn superoxide dismutase (SOD1)mutations underlie some cases of familial amyotrophic lateral sclerosis (ALS). Mutations cause a cytoxic gain-of-function of this antioxidant molecule that is expressed in the cytosol as well as the mitochondrial intramembrane space. Transgenic mice expressing high levels of stable human SOD1 (hSOD1) mutants become symptomatic, but the high expressed enzyme is Cu-deficient, and their intrasubunit disulfide bonds are reduced. This week, Bergemalm et al. show that these changes lead to nonphysiological mitochondrial loading of stable hSOD11 mutants, ∼100?fold higher than the endogenous mouse SOD1. In contrast, mice that expressed the unstable mutants G85R and G127X had 100- and 1000-fold lower mitochondrial hSOD1 levels, suggesting that unstable mutants do not cause disease by affecting mitochondria. The authors conclude that mitochondrial accumulation of SOD1 per se does not lead to motor neuron injury and that mitochondrial overloading may complicate interpretations of studies in mouse models expressing the stable mutants.
Total406 [ page11/28 ]
No. 제목 작성자 작성일 조회수
256 Congratulations to Sunghyun Kang 2007.02.22 한진 2007.02.22 1,926
255 Pancortin-2 interacts with WAVE1 and Bcl-xL in a mitochondria-associated protein complex that mediates ischemic neuronal death. 2007.02.20 한진 2007.02.20 2,170
254 ATP-sensitive potassium channel: A novel target for protection against UV-induced human skin cell damage. 2007.02.20 한진 2007.02.20 2,670
253 How To Spice Up Your Sex Life 첨부파일 2007.02.10 한진 2007.02.10 4,605
252 미토콘드리아(mitochondria)에 독성(toxicity)이 야기되면서 알츠하이머병(Alzheimer's disease) 2007.02.10 한진 2007.02.10 2,647
251 Mitochondrial DNA as a potential tool for early cancer detection 2007.02.10 한진 2007.02.10 2,019
250 A dream come true 2007.01.31 한진 2007.01.31 2,207
249 So how can chillies kill off cancer cells? 2007.01.31 한진 2007.01.31 1,900
248 A New Way to Fight Cancer? 2007.01.31 한진 2007.01.31 2,194
247 Glowing Reports From Mitochondria 2007.01.31 한진 2007.01.31 1,937
246 Congratulation!! Our paper posted "Most accessed articles in 2006" in Proteomics 첨부파일 2007.01.16 한진 2007.01.16 2,990
245 Preconditioning Enters the Era of "Physiological Proteomics" 2007.01.14 한진 2007.01.14 3,075
244 How spicy foods to kill cancer cells- Capsaicin!!! 첨부파일 2007.01.11 dang van cuong 2007.01.11 2,428
243 Researchers Uncover Mitochondrial Defect Involved With Inherited Cancers 2007.01.11 한진 2007.01.11 1,993
242 Coenzyme Q10 and Exercise Training Benefit Patients With Chronic Heart Failure 2007.01.11 한진 2007.01.11 1,805
처음 이전 11 12 13 14 15 16 17 18 19 20 다음 마지막