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The Journal of Neuroscience, June 3, 2009, 29(22)
This Week in The Journal
This Week in The Journal
Cellular/Molecular
Nicotine Increases SIDS Risk by Upregulating KATP Channels
Josef Buttigieg, Stephen Brown, Alison C. Holloway, and Colin A. Nurse
(see pages 7137–7147)
Infants born to mothers who smoke don't fare well when oxygen levels are low, placing them at increased risk for sudden infant death syndrome (SIDS). The response to low oxygen, or hypoxia, is regulated in infants by the adrenomedullary chromaffin cells of the adrenal gland. Hypoxia causes a decrease in potassium ion conductance in these cells, leading them to secrete catecholamines into the blood. Circulating catecholamines ensure that adequate blood flow to vital organs is maintained. Buttigieg et al. found that chronic maternal exposure to nicotine in rats increased the expression of ATP-sensitive potassium channels in the adrenomedullary chromaffin cells of the offspring. Increased activity of these channels counteracts any decrease in potassium conductance, thus impairing the normal response to hypoxia. A compound that blocks the activity of ATP-sensitive potassium channels reduced hypoxia-induced mortality in nicotine-exposed pups. Similar compounds may thus hold potential for treating infants at risk of SIDS resulting from nicotine exposure.
Development/Plasticity/Repair
Transcription Factor Smad1 Promotes Regeneration
Hongyan Zou, Carole Ho, Karen Wong, and Marc Tessier-Lavigne
(see pages 7116–7123)
Dorsal root ganglia neurons are a favored model system for studying regeneration in the nervous system. These neurons have an axon with two branches—a peripheral branch that innervates sensory organs and a central branch that relays information to the CNS. Severing the peripheral branch, but not the central branch, triggers axonal re-growth. By examining the expression of hundreds of dorsal root ganglia genes, Zou et al. found that the transcription factor Smad1 is expressed at higher levels following peripheral branch axotomy compared to central axotomy. Peripheral axotomy triggers the phosphorylation and nuclear translocation of Smad1, two events critical to its activity. Smad1 activity was then shown to be necessary and sufficient to push neurons into a growth state. Understanding how Smad1 and other factors regulate axon growth may provide ways to encourage growth of injured adult CNS neurons—which don't regenerate—and increase the regeneration capacity of peripheral neurons.
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The expression of the transcription factor Smad1 in dorsal root ganglia increases following axotomy of the peripheral branch, as revealed by in situ hybridization. See the article by Zou et al. for details.
Behavioral/Systems/Cognitive
Sleepless Flies Yield Insights into Insomnia
Laurent Seugnet, Yasuko Suzuki, Matthew Thimgan, Jeff Donlea, Sarah I. Gimbel, Laura Gottschalk, Steve P. Duntley, and Paul J. Shaw
(see pages 7148–7157)
Some flies, like humans, can have trouble getting enough shuteye. To gain a better understanding of sleep regulation, Seugnet et al. selected poor sleepers over 30 generations of the fruit fly Drosophila melanogaster. They obtained a strain, called insomnia-like (ins-l), that shares many traits with human insomnia, such as difficulties initiating and maintaining sleep, hyperactivity, trouble with learning, and poor motor coordination. Like insomniacs, ins-l flies have an increased risk of obesity and a decreased lifespan. When the researchers compared whole-genome expression profiles between ins-l and normal flies, they identified 1350 genes that are modified in the ins-l strain. Initial experiments indicated that the expression of two of these genes is also altered in sleep-deprived humans. This study may therefore serve to identify key players in the molecular underpinnings of insomnia, a disorder that affects 30–50% of the human population each year.
Neurobiology of Disease
PSD-95 Regulates Serotonin Receptor Expression
Atheir I. Abbas, Prem N. Yadav, Wei-Dong Yao, Margaret I. Arbuckle, Seth G. Grant, Marc G. Caron, and Bryan L. Roth
(see pages 7124–7136)
Many hallucinogenic and antipsychotic drugs target serotonin (5-hydroxytryptamine, or 5-HT) receptors. For example, the 5-HT2A receptors found in cortical neurons mediate the effects both of hallucinogenic drugs, like LSD (lysergic acid diethylamide), and of many so-called atypical antipsychotic drugs used to treat schizophrenia. 5-HT2A, and the closely related 5-HT2C receptor, also interact with the postsynaptic density protein of 95 kDa (PSD-95)—a protein involved in anchoring synaptic proteins. To examine the significance of this interaction, Abbas et al. used mutant mice lacking PSD-95. Without PSD-95, the expression of both the 5-HT2A and 5-HT2C receptors was dramatically reduced, most likely resulting from alterations in the receptors' turnover. In addition, the 5-HT2A receptor was no longer targeted to its appropriate dendritic compartment in neurons. Additional experiments indicated that PSD-95 is essential for the normal signaling of the 5-HT receptors. Indeed, antipsychotic drugs failed to normalize the psychotic-like behaviors in mice lacking PSD-95.
Related articles in J. Neurosci.:
- Axotomy-Induced Smad1 Activation Promotes Axonal Growth in Adult Sensory Neurons
- Hongyan Zou, Carole Ho, Karen Wong, and Marc Tessier-Lavigne
J. Neurosci. 2009 29: 7116-7123.[Abstract] [Full Text] - PSD-95 Is Essential for Hallucinogen and Atypical Antipsychotic Drug Actions at Serotonin Receptors
- Atheir I. Abbas, Prem N. Yadav, Wei-Dong Yao, Margaret I. Arbuckle, Seth G. N. Grant, Marc G. Caron, and Bryan L. Roth
J. Neurosci. 2009 29: 7124-7136.[Abstract] [Full Text] - Chronic Nicotine Blunts Hypoxic Sensitivity in Perinatal Rat Adrenal Chromaffin Cells via Upregulation of KATP Channels: Role of
7 Nicotinic Acetylcholine Receptor and Hypoxia-Inducible Factor-2
- Josef Buttigieg, Stephen Brown, Alison C. Holloway, and Colin A. Nurse
J. Neurosci. 2009 29: 7137-7147.[Abstract] [Full Text] - Identifying Sleep Regulatory Genes Using a Drosophila Model of Insomnia
- Laurent Seugnet, Yasuko Suzuki, Matthew Thimgan, Jeff Donlea, Sarah I. Gimbel, Laura Gottschalk, Steve P. Duntley, and Paul J. Shaw
J. Neurosci. 2009 29: 7148-7157.[Abstract] [Full Text]
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