Protein that Repairs Alzheimer’s Brain Damage Identified

TRENTON – Scientists from University of Medicine and Dentistry of New Jersey have identified a protein that can repair brain damage in Alzheimer’s patients.

They said that a protein called vimentin normally appears twice in a lifetime – when neurons in the brain are forming during the first years of life and, years later when the brain’s neurons are under siege from Alzheimer’s or other neurodegenerative diseases.

“Vimentin is expressed by neurons in regions of the brain where there is Alzheimer’s damage but not in undamaged areas of the brain,” said Dr Robert Nagele, a professor at UMDNJ and the study’s corresponding author.

“When the patient shows up at the doctor’s office with symptoms of cognitive impairment, the neurons have reached the point where they can no longer keep pace with the ever-increasing damage caused by Alzheimer’s,” he added.

While explaining the study results, Nagele likened neurons to a tree with long strands called dendrites branching off from the main part of the cell.

The dendrite branches are covered with 10,000 tiny “leaves” called synapses that allow neurons to communicate with each other. Vimentin is an essential protein for building the dendrite branches that support the synapses.

“A hallmark of Alzheimer’s is the accumulation of amyloid deposits that gradually destroy the synapses and cause the collapse of dendrite branches,” he said.

“When the dendrites and synapses degenerate, the neuron releases vimentin in an attempt to re-grow the dendrite tree branches and synapses. It’s a rerun of the embryonic program that allowed the brain to develop in the early years of life,” Nagele added.

The researchers also reported some initial findings that indicated a similar damage response mechanism takes place following traumatic brain injury, suggesting the possibility that similar therapeutic agents could be developed to enhance repair both for sudden brain trauma and for progressive neurodegenerative diseases.

The findings are published in journal Brain Research.

Cocaine Changes How Genes Work in Brain

Cocaine Changes How Genes Work in Brain

CHICAGO (Reuters) – Prolonged exposure to cocaine can cause permanent changes in the way genes are switched on and off in the brain, a finding that may lead to more effective treatments for many kinds of addiction, U.S. researchers said on Thursday.

A study in mice by Ian Maze of Mount Sinai School of Medicine in New York and colleagues found that chronic cocaine addiction kept a specific enzyme from doing its job of shutting off other genes in the pleasure circuits of the brain, making the mice crave the drug even more.

The study helps explain how cocaine use changes the brain, said Dr. Nora Volkow, director of the National Institute on Drug Abuse, part of the National Institutes of Health, which funded the study published in the journal Science.

“This finding is opening up our understanding about how repeated drug use modifies in long-lasting ways the function of neurons,” Volkow said in a telephone interview.

For the study, the team gave one group of young mice repeated doses of cocaine and another group repeated doses of saline, then a single dose of cocaine.

They found that one way cocaine alters the reward circuits in the brain is by repressing gene 9A, which makes an enzyme that plays a critical role in switching genes on and off.

Other studies have found that animals exposed to cocaine for a long period of time undergo dramatic changes in the way certain genes are turned on and off, and they develop a strong preference for cocaine.

This study helps explain how that occurs, Volkow said, and may even lead to new ways of overcoming addiction.

In the study, Maze and colleagues showed these effects could be reversed by increasing the activity of gene 9A.

“When they do that, they completely reverse the effects of chronic cocaine use,” Volkow said.

She said this mechanism is likely not confined to cocaine addiction, and could lead to a new area of addiction research for other drugs, alcohol and even nicotine addition.

“One of the questions we’ve had all along is, after discontinuing a drug, why do you continue to be addicted?

“This is one of the mechanisms that probably is responsible for these long-lasting modifications to the way people who are addicted to drugs perceive the world and react to it,” she said.

Source: Reuters

Gene That Controls Number of Brain Cells Identified

CHAROLETTE – Scientists from University of North Carolina have identified a gene that controls the number of cells composing brain.

Called GSK-3, the gene has been found to strike a balance between two key processes – proliferation, in which the cells multiply to provide plenty of starting materials, and differentiation, in which those materials evolve into functioning neurons.

If the stem cells proliferate too much, they could grow out of control and produce a tumour. If they proliferate too little, there may not be enough cells to become the billions of neurons of the brain.

The study showed that GSK-3 controls the signals that determine how many neurons actually end up composing the brain.

The novel findings may have significant implications for people suffering from neuropsychiatric illness like schizophrenia, depression, and bipolar disorder.

“I don’t believe anyone would have imagined that deleting GSK-3 would have such dramatic effects on neural stem cells,” Nature quoted senior study author Dr William D. Snider, professor of neurology and cell and molecular physiology, and director of the UNC Neuroscience Centre, as saying

“People will have to think carefully about whether giving a drug like lithium to children could have negative effects on the underlying structure of the nervous system,” he added.

During the study, the researchers genetically engineered mice to lack both forms of the GSK-3 gene, designated alpha and beta.

They further used a “conditional knock-out” strategy to remove GSK-3 at a specific time in the development of the mouse embryo, when a type of cell called a radial progenitor cell had just been formed.

“It was really quite striking,” said Snider.

“Without GSK-3, these neural stem cells just keep dividing and dividing and dividing. The entire developing brain fills up with these neural stem cells that never turn into mature neurons,” he added.

GSK-3 is known to coordinate signals for proliferation and differentiation within nerve cells through multiple “signalling pathways.”

They found that every one of the pathways that they studied went awry after deleting the GSK-3 gene.

The study has been published in the journal Nature Neuroscience.