Epilepsy linked to disruption of brain development during early childhood

August 25, 2009 By Leave a Comment

London, August 24 (ANI): Scientists at Beth Israel Deaconess Medical Center (BIDMC) say that a form of partial epilepsy, which is associated with auditory and other sensory hallucinations, may result from the disruption of brain development during early childhood.

The researchers claim that their findings provide the first genetic link between childhood brain development and a seizure disorder that lasts throughout adulthood, and also identify a new pathway that controls how neuron circuits are “pruned” and matured.

“During early childhood – roughly between the ages of one and five – the brain undergoes a period of major circuit remodeling,” Nature magazine quoted senior author Dr. Matthew Anderson, a principal investigator in the Departments of Neurology and Pathology at BIDMC, as saying.

“Our discovery that a familial form of temporal lobe epilepsy can develop at this point demonstrates the fragility of the brain during this critical period,” he added.

In their study report, the researchers have revealed that their findings focus on the development of synapses, the connections between brain cells.

“At birth, the brain is loaded with excitatory synapses which help make nerve cells ‘fire,’” says Anderson, who is also an Assistant Professor of Neurology and Pathology at Harvard Medical School.

“However, if these excess synapses are not adequately ‘pruned,’ they can overgrow, leading to excessive transmission of excitatory signals and the development of pathological conditions, including learning disabilities and autism in addition to epilepsy,” he adds.

Anderson has revealed that his study involved a genetically engineered mouse model, and and brain slice patch-clamp electrophysiology techniques.

He said that his team found that a mutant form of the LGI1 (leucine-rich glioma-inactivated 1) gene was preventing the normal brain development.

“The first clue was our discovery that LGI1 is not expressed until the exact time when excitatory synapses are matured. We subsequently learned that the mLGI1 gene was indeed prohibiting excitatory synapses from being adequately pruned, leading to an increased excitability of circuits in the brain which left it prone to excessive synchronous discharges that are characteristic of epilepsy,” said Anderson.

Autosomal dominant lateral temporal lobe epilepsy (ADLTE) is characterized by frequent partial seizures-two to five per month-that are associated with auditory or other sensory auras.

Tonic-clonic seizures also occur in the majority of ADLTE patients, but are infrequent, developing only about once a year.

“These partial seizures can have a significant impact on a patient’s quality of life. Because patients can be disoriented and excessively tired following a seizure event, their day-to-day lives can sometimes be seriously disrupted. And when it comes to driving and other activities, there is still a real danger associated with this condition,” notes Anderson.

“One important reason to identify genetic causes of epilepsy is the hope that these discoveries will eventually lead to new therapies. By identifying this new pathway, we may have found a new target for future drug development,” he adds.

A research article describing Anderson’s study has been published in the journal Nature Medicine. (ANI)

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Brain’s size does matter when it comes to intelligence

March 26, 2009 By Leave a Comment

Washington, March 26 (ANI): The brain’s size does matter when it comes to intelligence, if a new study led by researchers at the Montreal Neurological Institute (MNI), McGill University, is to be believed.

The researchers say that their study shows a positive link between cognitive ability and cortical thickness in the brains of healthy 6 to 18 year olds.

According to them, the correlation is evident in regions that integrate information from different parts of the brain.

The research team claim that theirs is the largest and most comprehensive of its kind with a representative sample of healthy children and adolescents.

The researchers gathered information about MRI scans and other data on the structure and function of the developing brains, which stemmed from the NIH MRI Study of Normal Brain Development.

They say that over 500 children and adolescents from newborns to 18-year-olds had brain scans multiple times over a period of years as well as intelligence, neuropsychological, verbal, non-verbal and behavioural tests.

The information contained within the database allowed the scientists to study how normal developmental changes in brain anatomy relate to motor and behavioural skills, such as motor coordination and language acquisition.

The team say that the database can be used even to assess higher-order skills like planning, IQ, and organizational skills.

The association between regional cortical thickness and intelligence has been little studied, and most previous studies of normal children had a relatively small sample.

The researchers said that their aim was to examine this relationship, and to further characterize and identify brain areas where cortical thickness was associated with cognitive performance.

They say that thicker cortices are likely to have more complex connections with consequences on cognitive ability.

During the study, a positive link between cortical thickness and cognitive ability was detected in many areas of the frontal, parietal, temporal, and occipital lobes.

The regions with the greatest relationship were the ‘multi-modal association’ areas, where information converges from various regions of the brain for processing, said the researchers.

“A principal finding of this study is that it supports a distributed model of intelligence where multiple areas of the brain are involved with cognitive ability difference instead of the view that there is just one centre or structure important for intelligence differences in the brain,” says Dr. Sherif Karama, psychiatrist at the MNI and co-investigator in the study.

“Previous studies have shown a link between intelligence differences and individual brain structure or function. This is the first time that a correlation between a general cognitive ability factor and essentially most, if not all, cortical association areas is demonstrated in the same study,” Karama adds.

A deeper insight into normal cognitive functioning and abilities is an important first step in the understanding of cognitive decline observed in the elderly as well as in those with various pathologies ranging from multiple sclerosis to schizophrenia, depression and mental retardation.

The team say that such an understanding may eventually lead to interventions that may be able to prevent or alleviate the decline or complications in cognitive function.

The study has been published in a special issue of scientific journal Intelligence. (ANI)

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Heavy marijuana use ‘damages teens’ brains’

February 3, 2009 By Leave a Comment

Washington, Feb 03 (ANI): A new study has revealed that teens and young adults who are heavy users of marijuana are more likely than non-users to have disrupted brain development.

In the study, researchers found abnormalities in areas of the brain that interconnect brain regions involved in memory, attention, decision-making, language and executive functioning skills.

The findings hold significance because adolescence is a crucial period for brain development and maturation.

“Studies of normal brain development reveal critical areas of the brain that develop during late adolescence, and our study shows that heavy cannabis use is associated with damage in those brain regions,” said study leader Manzar Ashtari, Ph.D., director of the Diffusion Image Analysis and Brain Morphometry Laboratory in the Radiology Department of The Children’s Hospital of Philadelphia.

In the study, Ashtari and colleagues performed imaging studies on 14 young men from a residential drug treatment center in New York State, as well as 14 age-matched healthy controls. All the study subjects were males, with an average age of 19.

The 14 subjects from the drug treatment center all had a history of heavy cannabis use during adolescence. On average, they had smoked marijuana from age 13 till age 18 or 19, and reported smoking nearly 6 marijuana joints daily in the final year before they stopped using the drug.

The researchers performed a type of magnetic resonance imaging scan called diffusion tensor imaging (DTI) that measures water movement through brain tissues.

“The abnormal patterns of water diffusion that we found among the young men with histories of marijuana use suggest damage or an arrest in development of the myelin sheath that surrounds brain cells,” said Ashtari.

Myelin provides a coating around brain cells similar to insulation covering an electrical wire. If myelin does not function properly, signaling within the brain may be slower. Myelin gives its colon to the white matter of the brain, and covers the nerve fibers that connect different brain regions.

“Our results suggest that early-onset substance use may alter the development of white matter circuits, especially those connections among the frontal, parietal and temporal regions of the brain. Abnormal white matter development could slow information transfer in the brain and affect cognitive functions,” said Ashtari.

Ashtari added that the findings are preliminary. Among other limitations of the study, such as a small sample size, five of the 14 subjects with heavy cannabis use also had a history of alcohol abuse, which may have contributed an effect.

Also, it is possible that the brain abnormalities may have predisposed the subjects to drug dependence, rather than drug usage causing the brain abnormalities.

“Further research should be done to investigate the relation between repeated marijuana use and white matter development. However, our work reinforces the idea that the adolescent brain may be especially vulnerable to risky behaviors such as substance abuse, because of crucial neural development that occurs during those years,” said Ashtari.

The study appeared early last month in the Journal of Psychiatric Research. (ANI)

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Biochemical switch needed for nerve cells to respond to DNA damage identified

January 19, 2009 By Leave a Comment

London, January 19 (ANI): Scientists at Emory University School of Medicine have announced the identification of a biochemical switch, which is required for nerve cells to respond to DNA damage.

The researchers say that their finding illuminates a connection between proteins involved in neurodegenerative disease and in cells’ response to DNA damage.

Most children who inherit the disease ataxia telangiectasia are rendered wheelchair-bound by the time they turn 10, because of neurological problems. Patients also have weakened immune systems and more frequent leukemias, and are more sensitive to radiation.

According to the researchers, the problem mainly results from mutations in the ATM (ataxia telangiectasia mutated) gene, which encodes an enzyme that controls cells’ response to and repair of DNA damage.

The researchers say that it is possible to turn on ATM by treating cells with chemicals that damage DNA. Once other proteins in the cell detect broken DNA needing repair, they say, the ATM protein could activate itself directly.

The team have shown that an additional step is necessary first.

“In neurons that are not dividing anymore, we now know that another regulator is involved: Cdk5,” Nature Cell Biology quoted says Dr. Zixu Mao, associate professor of pharmacology and neurology at Emory University School of Medicine, as saying.

Mao and his colleagues have found that the Cdk5 protein must activate ATM before the gene can do its job in neurons.

Based on their findings, the researchers came to the conclusion that Cdk5 may be a potential drug target.

Cdk5 contributes to normal brain development, and aberrant Cdk5 activity is known to be involved in the death of neurons in several neurodegenerative diseases, including Alzheimer’s, Parkinson’s and amyotrophic lateral sclerosis.

“Cdk5 has a complex character. It can be bad for neurons if its activity is either too high or too low,” Mao says.

Mao revealed that his team were intrigued by reports that in these diseases, neurons that had stopped dividing appear to restart that process, copying their DNA, before dying.

“That’s what really kicked us into high gear,” he says.

The same process, called mitotic catastrophe, occurs when neurons suffer DNA damage. Inhibiting either Cdk5 or ATM can reduce the number of neurons that suffer mitotic catastrophe after DNA damage, the authors found. (ANI)

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