Day: September 30, 2024

Categories : Neurology Substance UseTags : Leave a comment

Meth and PCP Cognitive Deficits Stem from a Common Neurotransmitter Switch

On By ModernMedia
Photo by Inzmam Khan

The effects of sustained drug abuse can manifest in many ways. Loss of memory and reduced cognitive functions are some of the effects that can persist for years. Neurobiologists at the University of California San Diego have now identified a mechanism in the brain that generates drug-induced cognitive impairments.

The researchers investigated how methamphetamine and phencyclidine (PCP or “angel dust”), which take effect by activating different targets in the brain, induce a similar reduction in cognitive ability. How could the same difficulties in memory emerge in response to drugs that trigger different actions in the brain?

The results of this investigation, led by Assistant Project Scientist Marta Pratelli in Professor Nicholas Spitzer’s laboratory, appear in Nature Communications. They showed that meth and PCP caused neurons to change the way they communicate through a process known as neurotransmitter switching.

Neurotransmitter switching is a form of brain plasticity, an evolving area of research investigating how the brain changes function and structure in response to experience. In recent years, Spitzer and his colleagues have also identified roles for neurotransmitter switching in autism spectrum disorder, post-traumatic stress disorder and in exercise.

Examining the cerebral cortex of mice, the investigators found that meth and PCP each caused a switch from the excitatory neurotransmitter glutamate to the inhibitory neurotransmitter GABA (gamma-aminobutyric acid) in the same neurons in the prelimbic region, an area of the frontal cortex involved in executive functions. This switch was linked to a decrease in memory task performance since drug-treated mice performed well in the tasks when the expression of GABA was blocked.

Further experiments showed that even after repeated exposure to the drugs, the researchers were able to reverse this neurotransmitter switch using molecular tools to locally decrease the brain’s electrical activity or using clozapine, an antipsychotic drug. Each of these treatments reversed the memory loss, restoring the performance of mice in the cognitive tasks.

“These results suggest that targeted manipulation of neuronal activity may be used to ameliorate some of the negative effects of repeated drug abuse,” said Pratelli.  

In this new study, the researchers found that a drug-induced increase in the release of dopamine, a neurotransmitter involved in reward, and an increase in the electrical activity of neurons in the cerebral cortex, were required to produce the neurotransmitter switch.

“This study reveals a shared and reversible mechanism that regulates the appearance of cognitive deficits upon exposure to different drugs,” said Spitzer.

The researchers note in their paper that a deeper understanding of brain mechanisms tied to loss of memory from drug use could boost prospects for new treatments, not only resulting in therapy for meth and PCP consumption, but for other disorders as well.

Source: University of San Diego California

Categories : Immune System Obstetrics & GynaecologyTags : Leave a comment

New Treatment for Pregnancy Loss Caused by Specific Autoantibody

On By ModernMedia
Photo by SHVETS production

Amongst women who experience recurrent pregnancy loss, around 20% test positive for a specific autoantibody. A Kobe University-led research team now found a treatment using either of two common drugs that drastically increases these women’s chances of carrying to full-term without complications, reporting their findings in Frontiers in Immunology.

Recurrent pregnancy loss is a condition of women who have lost two or more pregnancies for non-obvious reasons. Kobe University obstetrician Tanimura Kenji and his team have previously found that in 20% of these women, they can detect a specific antibody in their blood that targets their own bodies: anti-β2-glycoprotein I/HLA-DR autoantibodies.

Tanimura explains: “There is no known treatment for this particular condition, but the antibodies have a similar target to those that play a role in a different condition that has an established treatment.” Therefore, he wanted to test whether that treatment also works in the cases with the newly discovered antibody.

Tanimura enlisted the help of obstetricians across five hospitals in Japan and over the course of two years analysed the blood of consenting women suffering from recurrent pregnancy loss for the antibodies. If any of these women got pregnant during this time frame, their doctors would offer treatment options also containing those drugs that are effective against the chemically similar condition, specifically, low-dose aspirin or heparin. The research team then observed how many of the women who included these drugs in their treatment had full-term live births or pregnancy complications and compared that to the pregnancy outcomes in women who did not take either of the two drugs.

They report that women who received the treatment were much more likely to have live births (87% did) compared to the ones without treatment (of which only 50% had live births). In addition, amongst the live births, the treatment reduced the likelihood of complications from 50% to 6%. “The sample size was rather small (39 women received the treatment and 8 did not), but the results still clearly show that a treatment with low-dose aspirin or heparin is very effective in preventing pregnancy loss or complications also in women who have these newly discovered self-targeting antibodies,” summarises Tanimura.

Many women who tested positive for the newly discovered self-targeting antibodies also tested positive for the previously known ones. However, the Kobe University-led team found that women who only had the newly discovered antibodies and who received the treatment were even more likely to have a live birth (93%) and, amongst these, none had pregnancy complications.

Looking ahead, Tanimura says: “The newly discovered self-targeting antibody has been demonstrated to be involved also in infertility and recurrent implantation failure, as well as a risk factor for arterial thrombosis in women with systemic rheumatic diseases. I therefore expect that studies about the effectivity of the treatment against a broader range of conditions might produce encouraging results.”

Source: Kobe University

Categories : Endocrinology GastrointestinalTags : Leave a comment

The Gut Microbiome can Affect Symptoms of Hypopituitarism

On By ModernMedia
Gut Microbiome. Credit Darryl Leja National Human Genome Research Institute National Institutes Of Health

In research published in PLOS Genetics, scientists have shown that the balance of bacteria in the gut can influence symptoms of hypopituitarism in mice. They also showed that aspirin was able to improve hormone deficiency symptoms in mice with this condition.

People with mutations in a gene called Sox3 develop hypopituitarism, where the pituitary gland doesn’t make enough hormones. It can result in growth problems, infertility and poor responses of the body to stress.

The scientists at the at the Francis Crick Institute removed Sox3 from mice, causing them to develop hypopituitarism around the time of weaning (starting to eat solid food).

They found that mutations in Sox3 largely affect the hypothalamus in the brain, which instructs the pituitary gland to release hormones. However, the gene is normally active in several brain cell types, so the first task was to ask which specific cells were most affected by its absence.

The scientists observed a reduced number of cells called NG2 glia, suggesting that these play a critical role in inducing the pituitary gland cells to mature around weaning, which was not known previously. This could explain the associated impact on hormone production.

The team then treated the mice with a low dose of aspirin for 21 days. This caused the number of NG2 glia in the hypothalamus to increase and reversed the symptoms of hypopituitarism in the mice.

Although it’s not yet clear how aspirin had this effect, the findings suggest that it could be explored as a potential treatment for people with Sox3 mutations or other situations where the NG2 glia are compromised.

An incidental discovery revealed the role of gut bacteria in hormone production

When the National Institute for Medical Research (NIMR) merged with the Crick in 2015, mouse embryos were transferred from the former building to the latter, and this included the mice with Sox3 mutations.

When these mice reached the weaning stage at the Crick, the researchers were surprised to find that they no longer had the expected hormonal deficiencies.

After exploring a number of possible causes, lead author Christophe Galichet compared the microbiome – bacteria, fungi and viruses that live in the gut – in the mice from the Crick and mice from the NIMR, observing several differences in its makeup and diversity. This could have been due to the change in diet, water environment, or other factors that accompanied the relocation.

He also examined the number of NG2 glia in the Crick mice, finding that these were also at normal levels, suggesting that the Crick-fed microbiome was somehow protective against hypopituitarism.

To confirm this theory, Christophe transplanted faecal matter retained from NIMR mice into Crick mice, observing that the Crick mice once again showed symptoms of hypopituitarism and had lower numbers of NG2 glia. 

Although the exact mechanism is unknown, the scientists conclude that the make-up of the gut microbiome is an example of an important environmental factor having a significant influence on the consequences of a genetic mutation, in this case influencing the function of the hypothalamus and pituitary gland.

Source: Francis Crick Institute

Categories : Neurodegenerative DiseasesTags : Leave a comment

Two Treatments for Progressive Multiple Sclerosis Fail to Show Benefit

On By ModernMedia
This is a pseudo-colored image of high-resolution gradient-echo MRI scan of a fixed cerebral hemisphere from a person with multiple sclerosis. Credit: Govind Bhagavatheeshwaran, Daniel Reich, National Institute of Neurological Disorders and Stroke, National Institutes of Health

In people with primary progressive multiple sclerosis (MS), a new study has found no difference in the amount of time before disability worsened between people taking certain medications and those not receiving treatment. The study is published in Neurology®, the medical journal of the American Academy of Neurology.

With MS, the body’s immune system attacks the myelin sheaths of nerves. People with primary progressive MS experience a steady decline in symptoms. About 10 to 15% of people with the disease have this type of MS.

The study looked at rituximab and ocrelizumab, anti-CD20 infusion therapies that target a protein called CD20 found on some white blood cells called B-cells. Removing these cells from the bloodstream is believed to reduce inflammation and damage that can occur to the myelin.

Ocrelizumab is approved by the US Food and Drug Administration (FDA) for primary progressive MS and for people with relapses, but rituximab is not. Rituximab is FDA approved for other diseases like rheumatoid arthritis and prescribed off label for MS in the US.

“MS is a disabling disease, so treatments that slow the progression to worse disability are sorely needed,” said study author Laure Michel, MD, PhD, of Rennes University in France. “Anti-CD20 therapies are widely prescribed, in part because there are few alternate treatments. However, our study suggests they may not slow disability from worsening for people with primary progressive MS.”

The study involved 1184 people with primary progressive MS who had an average age of 56. They did not take MS medications in the two years prior to the study. For the study, 295 people were treated with rituximab, 131 were treated with ocrelizumab and 728 were untreated.

They were followed for an average of four years. Participants’ level of disability was measured on a scale with scores ranging from zero, meaning no symptoms, to 10 points, meaning death due to MS. At the start of the study, all participants had a score of 6.5 or less. Researchers then measured how long it took for people to advance to their first confirmed disability progression.

For those whose score was less than 5.5 at the start of the study, advancing one point on the scale was considered progressing in disability. If their score was 5.5 or more, advancing 0.5 points on the scale was disability progression.

After adjusting for possible differences between the treated and untreated groups, researchers found there was no difference in the time it took to progress to the next level of disability between those taking a medication and those taking no medication. “

Medications for MS can be expensive and come with risks of side effects,” said Michel. “Our results indicate that there should be a constant evaluation of MS therapies to determine if the benefits outweigh the risks for people with primary progressive MS.”

A limitation of the study was that it was retrospective and did not follow people in real time. Also, among those taking medications, most were taking rituximab with fewer people taking ocrelizumab. More research is needed in larger groups of people to confirm the findings.

Source: American Academy of Neurology

Categories : Cardiovascular Disease Obstetrics & GynaecologyTags : Leave a comment

Heart Defects in Babies Born after Fertility Treatment are More Common

On By ModernMedia
Intracytoplasmic Sperm Injection (ICSI) procedure. Credit: Scientific Animations CC4.0

The risk of being born with a major heart defect is 36% higher in babies who were conceived after assisted reproductive technology, such as in vitro fertilisation (IVF), according to results of a very large study published in the European Heart Journal.

Researchers say the finding is important since congenital heart defects are the most common form of birth defects, and some of them are associated with life threatening complications.

The study also shows that the increase in risk is particularly associated with multiple births which are more common in assisted reproduction.

 The study was led by Professor Ulla-Britt Wennerholm from the University of Gothenburg in Sweden. She said: “Previous research shows that there are increased risks for babies conceived with the help of assisted reproductive technology. These include preterm birth and low birth weight. We wanted to investigate whether the risk of heart defects was higher for babies born following assisted reproduction.”

The research included all liveborn children born in Denmark between 1994 and 2014, all children born in Finland between 1990 and 2014, those born in Norway between 1984 and 2015 and those born in Sweden from 1987 to 2015; more than 7.7 million in total.

Researchers compared data on babies born following assisted reproduction, including IVF, intracytoplasmic sperm injection (ICSI) and embryo freezing, with data on babies conceived naturally.

They assessed how many liveborn children in each group were diagnosed with a major heart defect or with a serious heart defect either in the womb or in the first year of life. They took into account other factors that can increase the risk of congenital heart defects, such as child’s year of birth, country of birth, mother’s age at delivery, if the mother smoked during pregnancy, or if the mother had diabetes or heart defects.

This showed that heart defects were around 36% more common in babies born after assisted reproduction, compared to babies conceived without such treatment (absolute risk 1.84% vs 1.15%). This risk was similar regardless of the type of assisted reproduction used (IVF or ICSI, fresh or frozen embryos). However, the risk was greater for multiple births following assisted reproduction compared to singleton births following assisted reproduction (2.47% vs 1.62%).

Professor Wennerholm said: “We already know that babies born after assisted reproductive technology have a higher risk of birth defects in general however, we have found a higher risk also in congenital heart defects, the most common major birth defect.

“The fact that the risk of heart defects is similar regardless of the type of assisted reproduction used may indicate that there is some common factor underlying infertility in parents and congenital heart disease in their babies.

“Congenital heart defects can be extremely serious requiring specialist surgery when babies are very young, so knowing which babies are at the greatest risk can help us diagnose heart defects as early as possible and ensure the right care and treatment are given. More and more people are conceiving with the help of assisted reproductive technology, so we might expect to see increases in cases of congenital heart defects worldwide.”

In an accompanying editorial, Dr Nathalie Auger from University of Montreal Hospital Research Centre in Canada and colleagues said: “Assisted reproductive technology is a popular intervention in reproductive medicine, with these procedures accounting for 2% to 8% of births depending on the country. While most neonates born after assisted reproductive technology are healthy, these procedures are not without risks.

“In one of the largest studies to date, the researchers found that assisted reproductive technology was associated with the risk of major heart defects diagnosed prenatally or up to one year of age.

“Patients who use assisted reproductive technology tend to differ from the general population. These patients may have underlying morbidities that affect both fertility and the risk of heart defects.”

Source: European Society of Cardiology