Monday, August 23, 2010
Monday, August 16, 2010
MeCP2 controls BDNF expression and cocaine intake through homeostatic interactions with microRNA-212
Very recent and interesting article by team of "The Scripps Research Institute–Scripps Florida"
Authors:
Heh-In Im, Jonathan A Hollander, Purva Bali & Paul J Kenny
Source: Nature Neuroscience
Note: Click on the title to read full article
Authors:
Heh-In Im, Jonathan A Hollander, Purva Bali & Paul J Kenny
Source: Nature Neuroscience
Note: Click on the title to read full article
MeCP2 in the nucleus accumbens contributes to neural and behavioral responses to psychostimulants
Very interesting study by Deng et al., 2010
Source: Nature neuroscience
Note: click on the title to read full article
Source: Nature neuroscience
Note: click on the title to read full article
Friday, August 13, 2010
Cocaine Addiction Linked to Protein That Causes Rett Syndrome
Drug Discovery & Development - August 11, 2010
Scientists from the Florida campus of The Scripps Research Institute have identified a protein that may act as the trigger controlling the addictive impact of cocaine in the brain. The findings may one day lead to new therapies to treat addiction.
The study was published on August 15, 2010, in the journal Nature Neuroscience.
The results from the new study strongly suggest that a protein known as methyl CpG binding protein 2 (MeCP2) interacts with a type of genetic material known as microRNA to control an individual’s motivation to consume cocaine.
“The study shows that MeCP2 blunts the amount by which microRNA-212 is increased in response to cocaine,” said Paul Kenny, an associate professor in the Department of Molecular Therapeutics at Scripps Florida who led the study. “We have previously shown that miR-212 is very protective against cocaine addiction. Therefore, the conclusion is that MeCP2 may regulate vulnerability to addiction in some people through its inhibitory influence on miR-212. Without this influence, the expression of miiR-212 would be far greater in response to cocaine use, and the risk of addiction would likely be far lower.”
This is the first time that MeCP2 has been shown to play a role in regulating cocaine addiction. Previously, the protein was most linked to Rett syndrome, a progressive neurodevelopmental disorder and one of the most common causes of mental retardation in females.
Interactions Shape Vulnerability
These new findings come on the heels of another cocaine addiction study by Kenny and his Scripps Florida colleagues published in the journal Nature in early July. That study showed for the first time that miR-212 — a type of small non-protein coding RNA that can regulate the expression levels of hundreds or even thousands of genes —influenced response to the drug in rats. Animals with increased miR-212 expression were less motivated to consume cocaine, pointing to the protective effects of miR-212 against cocaine addiction.
“The new findings are a significant advance from this previous study,” Kenny said, “because they clearly demonstrate why microRNA-212 is not always fully protective – because MeCP2 regulates by how much miR-212 levels will increase in response to cocaine. This suggests that our initial findings may be central to explaining the complex process of addiction, and understanding how miR-212 signaling is regulated will be important. This study adds another level of detail to the blueprint.”
A major goal of drug abuse research is to understand why certain individuals make the switch from casual to compulsive drug use and develop into addicts. Periods of easy access to the drug, along with repeated overconsumption, can quickly trigger the emergence of addiction-like abnormalities in animal models.
In the new study, the scientists first looked at the expression of MeCP2 in the brain after exposure to cocaine. They found that expression was increased in those animals given extended access to the drug.
“At that point,” Kenny said, “we wanted to know if this increase was behaviorally significant – did it influence the motivation to take the drug?"
Using a virus to disrupt expression of MeCP2, the scientists found that rats consumed less and less cocaine. Intriguingly, levels of miR-212 were also far higher in those animals. Because increases in miR-212 suppress attraction to cocaine, the disruption of MeCP2, in essence, put miR-212 in charge and reduced vulnerability to the drug.
“We concluded that MeCP2 may play an important role in addiction by regulating the magnitude by which miR-212 expression is increased in response to cocaine," said Kenny. "In other words, MeCP2 seems to control just how much you can protect yourself against the addictive properties of cocaine."
Intriguingly, that was not the end of the story. In addition to MeCP2 blunting miR-212 expression, the scientists also found that the opposite was also true – that miR-212 could in turn decrease levels of MeCP2. This suggests that both are locked together in a regulatory loop. Importantly, the two had opposite effects on the expression of a particular growth factor in the brain – called BDNF – that regulates just how rewarding cocaine is.
While the new study fills in an important piece of the puzzle, the Kenny lab is hard at work to further increase our understanding of addiction.
“We still don’t know what exactly influences the activity levels of MeCP2 on miR-212 expression,” Kenny said. “Now we plan to explore what drives it – whether it’s environmentally driven, and if genetic and epigenetic influences are important.”
Source: The Scripps Research Institute
Scientists from the Florida campus of The Scripps Research Institute have identified a protein that may act as the trigger controlling the addictive impact of cocaine in the brain. The findings may one day lead to new therapies to treat addiction.
The study was published on August 15, 2010, in the journal Nature Neuroscience.
The results from the new study strongly suggest that a protein known as methyl CpG binding protein 2 (MeCP2) interacts with a type of genetic material known as microRNA to control an individual’s motivation to consume cocaine.
“The study shows that MeCP2 blunts the amount by which microRNA-212 is increased in response to cocaine,” said Paul Kenny, an associate professor in the Department of Molecular Therapeutics at Scripps Florida who led the study. “We have previously shown that miR-212 is very protective against cocaine addiction. Therefore, the conclusion is that MeCP2 may regulate vulnerability to addiction in some people through its inhibitory influence on miR-212. Without this influence, the expression of miiR-212 would be far greater in response to cocaine use, and the risk of addiction would likely be far lower.”
This is the first time that MeCP2 has been shown to play a role in regulating cocaine addiction. Previously, the protein was most linked to Rett syndrome, a progressive neurodevelopmental disorder and one of the most common causes of mental retardation in females.
Interactions Shape Vulnerability
These new findings come on the heels of another cocaine addiction study by Kenny and his Scripps Florida colleagues published in the journal Nature in early July. That study showed for the first time that miR-212 — a type of small non-protein coding RNA that can regulate the expression levels of hundreds or even thousands of genes —influenced response to the drug in rats. Animals with increased miR-212 expression were less motivated to consume cocaine, pointing to the protective effects of miR-212 against cocaine addiction.
“The new findings are a significant advance from this previous study,” Kenny said, “because they clearly demonstrate why microRNA-212 is not always fully protective – because MeCP2 regulates by how much miR-212 levels will increase in response to cocaine. This suggests that our initial findings may be central to explaining the complex process of addiction, and understanding how miR-212 signaling is regulated will be important. This study adds another level of detail to the blueprint.”
A major goal of drug abuse research is to understand why certain individuals make the switch from casual to compulsive drug use and develop into addicts. Periods of easy access to the drug, along with repeated overconsumption, can quickly trigger the emergence of addiction-like abnormalities in animal models.
In the new study, the scientists first looked at the expression of MeCP2 in the brain after exposure to cocaine. They found that expression was increased in those animals given extended access to the drug.
“At that point,” Kenny said, “we wanted to know if this increase was behaviorally significant – did it influence the motivation to take the drug?"
Using a virus to disrupt expression of MeCP2, the scientists found that rats consumed less and less cocaine. Intriguingly, levels of miR-212 were also far higher in those animals. Because increases in miR-212 suppress attraction to cocaine, the disruption of MeCP2, in essence, put miR-212 in charge and reduced vulnerability to the drug.
“We concluded that MeCP2 may play an important role in addiction by regulating the magnitude by which miR-212 expression is increased in response to cocaine," said Kenny. "In other words, MeCP2 seems to control just how much you can protect yourself against the addictive properties of cocaine."
Intriguingly, that was not the end of the story. In addition to MeCP2 blunting miR-212 expression, the scientists also found that the opposite was also true – that miR-212 could in turn decrease levels of MeCP2. This suggests that both are locked together in a regulatory loop. Importantly, the two had opposite effects on the expression of a particular growth factor in the brain – called BDNF – that regulates just how rewarding cocaine is.
While the new study fills in an important piece of the puzzle, the Kenny lab is hard at work to further increase our understanding of addiction.
“We still don’t know what exactly influences the activity levels of MeCP2 on miR-212 expression,” Kenny said. “Now we plan to explore what drives it – whether it’s environmentally driven, and if genetic and epigenetic influences are important.”
Source: The Scripps Research Institute
Wednesday, August 11, 2010
Yet Another Door Opens: Neuroimmunology: Rett Syndrome Research Trust Interview Series
Considering Microglia, T Cells and Bone Marrow Transplants in Rett Syndrome
Today we interview Jonathan Kipnis, PhD, a neuroimmunologist who is looking at how the immune system interacts with the nervous system in Rett Syndrome, and is experimenting with ways to engage that interaction to impact Rett symptoms. The immune system is complex and multifaceted, with inflammatory and anti-inflammatory actions and modulatory influences on various other substances, including neurotrophic factors such as BDNF, familiar to parents who follow Rett research. RSRT is supporting his innovative exploration of bone marrow transplants in Rett models.
..........
To read full Interview, please click on the title
Source: Rett Syndrome Research Trust
Today we interview Jonathan Kipnis, PhD, a neuroimmunologist who is looking at how the immune system interacts with the nervous system in Rett Syndrome, and is experimenting with ways to engage that interaction to impact Rett symptoms. The immune system is complex and multifaceted, with inflammatory and anti-inflammatory actions and modulatory influences on various other substances, including neurotrophic factors such as BDNF, familiar to parents who follow Rett research. RSRT is supporting his innovative exploration of bone marrow transplants in Rett models.
..........
To read full Interview, please click on the title
Source: Rett Syndrome Research Trust
Tuesday, August 3, 2010
Father’s mission to find a cure for his girl
A DAD has helped set up a charity for his disabled daughter, who suffers from a rare genetic condition.
Andy Stevenson, aged 41, of Pinewood Road, Burtonwood, registered the Rett Syndrome Research Trust (RSRT) UK for 10-year-old Beth, who suffers from the neurological disease, which causes severe physical and learning difficulties.
‘A cure for Rett syndrome is possible in the near future. I am keen to do all I can to help that happen ...'
Andy Stevenson
Rett syndrome, which has no cure, is an autism spectrum disorder that can develop in otherwise healthy young girls, just as they are beginning to speak and walk, robbing them of these emerging skills.
Beth needs 24-hour care, spends most of her time in a wheelchair, is unable to speak and suffers from epilepsy.
Andy, a golf pro at Mersey Valley Golf and Country Club who is married to Lisa, aged 42, said: “All the trustees are very excited that we are up and running. A cure for Rett syndrome is possible in the near future.
“I am keen to do all I can to help that happen for Beth and future generations.”
Andy founded the charity with five other families affected by Rett syndrome and he hopes their efforts will lead to improved treatments to ensure it becomes the first ever reversible brain disorder.
To help achieve this RSRT UK will work closely with a US partner of the same name.
The organisation’s first event, a gala reception, is planned for November 18, and will be held in London with guest of honour Professor Adrian Bird of the University of Edinburgh, who is a scientific advisor to the trust.
Rachael Bloom, chairman of the board of trustees who has a 14-year-old daughter who suffers with the disorder, said: “RSRT UK formed when a group of families came together with the belief that parents must take an active role in the fight against Rett syndrome.
“We want to see this research driven to its conclusion, replicating the results of the reversal experiments not in mice, but in girls and women living with Rett syndrome today.”
When Beth was diagnosed in 2002, Andy’s fundraising challange saw him take part in the Leeds and Loch Ness marathons. He also completed a gruelling assault course called Tough Guy, which took place in Wolverhampton in January and involved running through fire and crawling under barbed wire.
For more information visit reverserett.org.uk
Source:# This Is Cheshire » News
Andy Stevenson, aged 41, of Pinewood Road, Burtonwood, registered the Rett Syndrome Research Trust (RSRT) UK for 10-year-old Beth, who suffers from the neurological disease, which causes severe physical and learning difficulties.
‘A cure for Rett syndrome is possible in the near future. I am keen to do all I can to help that happen ...'
Andy Stevenson
Rett syndrome, which has no cure, is an autism spectrum disorder that can develop in otherwise healthy young girls, just as they are beginning to speak and walk, robbing them of these emerging skills.
Beth needs 24-hour care, spends most of her time in a wheelchair, is unable to speak and suffers from epilepsy.
Andy, a golf pro at Mersey Valley Golf and Country Club who is married to Lisa, aged 42, said: “All the trustees are very excited that we are up and running. A cure for Rett syndrome is possible in the near future.
“I am keen to do all I can to help that happen for Beth and future generations.”
Andy founded the charity with five other families affected by Rett syndrome and he hopes their efforts will lead to improved treatments to ensure it becomes the first ever reversible brain disorder.
To help achieve this RSRT UK will work closely with a US partner of the same name.
The organisation’s first event, a gala reception, is planned for November 18, and will be held in London with guest of honour Professor Adrian Bird of the University of Edinburgh, who is a scientific advisor to the trust.
Rachael Bloom, chairman of the board of trustees who has a 14-year-old daughter who suffers with the disorder, said: “RSRT UK formed when a group of families came together with the belief that parents must take an active role in the fight against Rett syndrome.
“We want to see this research driven to its conclusion, replicating the results of the reversal experiments not in mice, but in girls and women living with Rett syndrome today.”
When Beth was diagnosed in 2002, Andy’s fundraising challange saw him take part in the Leeds and Loch Ness marathons. He also completed a gruelling assault course called Tough Guy, which took place in Wolverhampton in January and involved running through fire and crawling under barbed wire.
For more information visit reverserett.org.uk
Source:# This Is Cheshire » News
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