How to generate new neurons in the brain

 Some areas of the adult brain contain quiescent, or dormant, neural stem cells that can potentially be reactivated to form new neurons. However, the transition from quiescence to proliferation is still poorly understood. A team led by scientists from the Universities of Geneva (UNIGE) and Lausanne (UNIL) has discovered the importance of cell metabolism in this process and identified how to wake up these neural stem cells and reactivate them. Biologists succeeded in increasing the number of new neurons in the brain of adult and even elderly mice. These results, promising for the treatment of neurodegenerative diseases, are to be discovered in the journal Science Advances.

Stem cells have the unique ability to continuously produce copies of themselves and give rise to differentiated cells with more specialized functions. Neural stem cells (NSCs) are responsible for building the brain during embryonic development, generating all the cells of the central nervous system, including neurons.

Neurogenesis capacity decreases with age

Surprisingly, NSCs persist in certain brain regions even after the brain is fully formed and can make new neurons throughout life. This biological phenomenon, called adult neurogenesis, is important for specific functions such as learning and memory processes. However, in the adult brain, these stem cells become more silent or ''dormant'' and reduce their capacity for renewal and differentiation. As a result, neurogenesis decreases significantly with age.The laboratories of Jean-Claude Martinou, Emeritus Professor in the Department of Molecular and Cellular Biology at the UNIGE Faculty of Science, and Marlen Knobloch, Associate Professor in the Department of Biomedical Sciences at the UNIL Faculty of Biology and Medicine, have uncovered a metabolic mechanism by which adult NSCs can emerge from their dormant state and become active.

''We found that mitochondria, the energy-producing organelles within cells, are involved in regulating the level of activation of adult NSCs,'' explains Francesco Petrelli, research fellow at UNIL and co-first author of the study with Valentina Scandella. The mitochondrial pyruvate transporter (MPC), a protein complex discovered eleven years ago in Professor Martinou's group, plays a particular role in this regulation. Its activity influences the metabolic options a cell can use. By knowing the metabolic pathways that distinguish active cells from dormant cells, scientists can wake up dormant cells by modifying their mitochondrial metabolism.

New perspectives

Biologists have blocked MPC activity by using chemical inhibitors or by generating mutant mice for the Mpc1gene. Using these pharmacological and genetic approaches, the scientists were able to activate dormant NSCs and thus generate new neurons in the brains of adult and even aged mice. ''With this work, we show that redirection of metabolic pathways can directly influence the activity state of adult NSCs and consequently the number of new neurons generated,'' summarizes Professor Knobloch, co-lead author of the study. ''These results shed new light on the role of cell metabolism in the regulation of neurogenesis. In the long term, these results could lead to potential treatments for conditions such as depression or neurodegenerative diseases'', concludes Jean-Claude Martinou, co-lead author of the study.

Journal Reference:

1. Francesco Petrelli, Valentina Scandella, Sylvie Montessuit, Nicola Zamboni, Jean-Claude Martinou, Marlen Knobloch. Mitochondrial pyruvate metabolism regulates the activation of quiescent adult neural stem cells. Science Advances, 2023; 9 (9) DOI: 10.1126/sciadv.add5220

https://www.sciencedaily.com/releases/2023/03/230301141432.htm

High blood pressure during pregnancy linked to thinking problems later

 High blood pressure disorders during pregnancy are associated with an increased risk of thinking problems later in life, according to a study published in the March 1, 2023, online issue of Neurology®, the medical journal of the American Academy of Neurology. Researchers found that those with these disorders had a higher risk of cognitive problems in later life than those who did not have high blood pressure during pregnancy. They also found that those with preeclampsia, which is high blood pressure that develops halfway through pregnancy and usually involves the kidneys and other organs, may have an even greater risk of cognitive decline later in life, compared to those with gestational high blood pressure, a condition with high blood pressure in pregnancy but without affecting the kidneys or other organs.

"While high blood pressure during pregnancy, including preeclampsia, is recognized as a risk factor for heart disease and stroke, our study suggests that it may also be a risk factor for cognitive decline in later life," said study author Michelle M. Mielke, PhD, of Wake Forest University School of Medicine in Winston-Salem, North Carolina, and a member of the American Academy of Neurology.

The study involved 2,239 female participants with an average age of 73. Researchers looked at medical records for information about previous pregnancies.

Of the participants, 1,854 people or 83% had at least one pregnancy, and 385 people or 17% never had a pregnancy or had a pregnancy of less than 20 weeks. Of those with pregnancies longer than 20 weeks, 100 had gestational high blood pressure, 147 had preeclampsia or eclampsia and 1,607 had normal blood pressure. Preeclampsia is when there is excess protein in the urine during pregnancy. Eclampsia is when high blood pressure during pregnancy causes one or more seizures, sometimes followed by a coma.

For the study, participants took nine memory and thinking tests every 15 months over an average of five years. The tests measured thinking and memory skills including global cognition, processing speed, executive function, language and visual perception.

Overall, researchers found that those with high blood pressure during pregnancy had a greater decline than those without high blood pressure during pregnancy and those who had not given birth on tests of global cognition, attention, executive function and language.

After adjusting for age and education, the average composite score of all memory and thinking tests of participants with any type of high blood pressure disorder had a decline of 0.3 points compared to those who did not have high blood pressure during pregnancy with a decline of 0.05 points. When looking at different types of high blood pressure disorders, those with preeclampsia had a decline of 0.04 points compared to those with other blood pressure disorders and those with no blood pressure disorders, which both had a decline of 0.05.

After adjusting for age and education, those with high blood pressure in pregnancy declined 0.4 standard deviation over five years on tests of executive function and attention, compared to those who had normal blood pressure for all pregnancies and declined only 0.1 standard deviation. These results were more pronounced for those who had preeclampsia, with a 0.5 standard deviation decrease on tests of executive function and attention compared to a 0.1 decrease for those who had normal blood pressure for all pregnancies.

"More research is needed to confirm our findings. However, these results suggest that managing and monitoring blood pressure during and after pregnancy is an important factor for brain health later in life," Mielke said.

A limitation of the study is that most of the participants were white, so results may not be generalizable to more diverse populations that have higher rates of high blood pressure in pregnancy.

The study was funded by National Institutes of Health and the Gerald and Henrietta Rauenhorst Foundation.

Journal Reference:

1. Calin I Prodan. Bridging the Gap Between Hypertensive Disorders of Pregnancy and Cognitive Decline in Older Women. Neurology, 2023 DOI: 10.1212/WNL.0000000000207237

https://www.sciencedaily.com/releases/2023/03/230301162703.htm

Physical activity can help mental health in pre-teen years

 Regular physical activity can improve adolescents' mental health and help with behavioural difficulties, research suggests.

Engaging in regular moderate to vigorous physical activity at age 11 was associated with better mental health between the ages of 11 and 13, the study found.

Physical activity was also associated with reduced hyperactivity and behavioural problems, such as loss of temper, fighting with other children, lying, and stealing, in young people.

Researchers from the Universities of Edinburgh, Strathclyde, Bristol, and Georgia in the United States explored data from the Children of the 90s study (also known as the Avon Longitudinal Study of Parents and Children; ALSPAC). They looked at the levels of physical activity of 4755 11-year-olds which was measured using devices.

The devices recorded levels of moderate physical activity -- typically defined as brisk walking or cycling -- as well as vigorous activity which boosts heart rate and breathing, such as aerobic dancing, jogging or swimming.

The young people and their parents reported on their levels of depressive symptoms from age 11 and at age 13 years. Participants' parents and teachers were also quizzed about the young people's general behaviour and emotional difficulties.

In analysing the impact of moderate to vigorous exercise on the young people's mental health and behaviour, the team also considered factors such as age, sex and socio-economic status.

They found that higher levels of moderate or intense physical activity had a small but detectable association with decreases in depressive symptoms and emotional difficulties.

Regular exercise had a small but detectable association with reduced behavioural problems, even after controlling for other possible influences, the study found.

The findings suggest regular moderate and intense physical activity may have a small protective influence on mental health in early adolescence, researchers say.

Dr Josie Booth, of the University of Edinburgh's Moray House School of Education and Sport, said: "This study adds to the increasing evidence base about how important physical activity is for all aspects of young people's development -- it can help them feel better, and do better at school. Supporting young people to lead healthy active lives should be prioritised."

Researchers say the study is the first to offer such a comprehensive approach to examining mental health and exercise in young people.

Professor John Reilly, at the University of Strathclyde, said: "While it might seem obvious that physical activity improves mental health the evidence for such a benefit in children and young people has been scarce, so the study findings are important. The findings are also important because levels of moderate-to-vigorous intensity activity globally are so low in pre-teens globally -- less than a third achieve the 60 minutes per day recommended by the WHO and UK Health Departments."

The study is published in Mental Health and Physical Activity.

The research was funded by the Bupa Foundation. Researchers used data from the Children of the 90s study, also known as the ALSPAC birth cohort, based at the University of Bristol. The study is a long-term health-research project that enrolled more than 14,000 pregnant women in 1991 and 1992.

Children of the 90s has been following the health and development of the parents and their children in detail and is currently recruiting the children and the siblings of the original children into the study. It receives core funding from the Medical Research Council, the Wellcome Trust and the University of Bristol.

Journal Reference:

1. Josephine N. Booth, Andy R. Ness, Carol Joinson, Phillip D. Tomporowski, James M.E. Boyle, Sam D. Leary, John J. Reilly. Associations between physical activity and mental health and behaviour in early adolescence. Mental Health and Physical Activity, 2023; 24: 100497 DOI: 10.1016/j.mhpa.2022.100497

https://www.sciencedaily.com/releases/2023/03/230301210307.htm

Fledgling chronic back pain therapy needs more rigorous study

 A systematic review of relatively new treatment for chronic back pain -- Cognitive Functional Therapy -- has found that it is no better than traditional therapies based on evidence from past studies.

Leading the review was Mr Jack Devonshire, a PhD candidate with UNSW Sydney and Neuroscience Research Australia (NeuRA). He looked at studies of Cognitive Functional Therapy (CFT) as a treatment for chronic back pain which, for the purposes of his research, was defined as pain experienced continuously for three months or more in the region between the 12th rib and the crease of the buttocks.

CFT has been growing in popularity and gaining attention among practitioners since the first clinical trial in 2013 based on theory developed in 2005. There have been multiple trials across the world on CFT since, says Mr Devonshire.

"CFT integrates treatments that may be helpful in managing chronic lower back pain, such as pain education, exercise, and lifestyle coaching, into a model of care informed by a contemporary understanding of a person's entire pain experience," he says.

"The therapy aims to build upon the biopsychosocial model to provide health professionals with what we call a clear 'clinical reasoning framework' to tailor strategies to manage this chronic condition."

Global interest in CFT

Despite the therapy being integrated into healthcare systems in the UK and Finland, as well as having multiple training courses online for clinicians, there hasn't yet been a comprehensive analysis of research into this therapy.

"So we decided to perform a systematic review and meta-analysis, the highest level of evidence, to look at past studies to find out how effective the treatment is on pain, disability and safety," Mr Devonshire says.

After examining all the studies that fit the research criteria, Mr Devonshire and his fellow authors found that ultimately the effectiveness of CFT remains unknown at this stage, and the group calls for future trials featuring blinded participants -- those who are unaware whether the therapy being administered is actual or sham -- and studies that recruit larger sample sizes.

"The results of our study found that CFT may not reduce pain intensity and disability in people with chronic low back pain, compared to manual therapy and core exercises, either at the end of treatment or at the 12-month follow-up," Mr Devonshire says.

"This is important as we want our exercise physiologists, physios and other health professionals who manage people with low back pain to be armed with the best available information on the available effective treatments -- especially since learning to deliver CFT as a therapist is quite intensive, taking an average 106 hours of training to properly deliver the treatment."

The researchers otherwise found that no adverse events were reported among patients after receiving the CFT treatment.

Mr Devonshire notes that certainty in the researchers' systematic review was limited by differences between study controls, small sample sizes and a high risk of bias across all included studies, impacting the trustworthiness of the findings from these studies. The group looks forward to further research that improves current evidence via clinical trials on CFT.

The review was published recently in the Journal of Orthopaedic & Sports Physical Therapy.

Journal Reference:

1. Jack J Devonshire, Michael A Wewege, Harrison J Hansford, Hasibe A Odemis, Benedict M Wand, Matthew D Jones, James H McAuley. Effectiveness of cognitive functional therapy for reducing pain and disability in chronic low back pain: a systematic review and meta-analysis. Journal of Orthopaedic & Sports Physical Therapy, 2023; 1 DOI: 10.2519/jospt.2023.11447

https://www.sciencedaily.com/releases/2023/03/230302093411.htm

Feinstein, Fetterman Hospitalizations May Mean Trouble For Dems

 by Jack Phillips via The Epoch Times (emphasis ours),

Senate Democrats have little room for error after Sen. Dianne Feinstein (D-Calif.) announced she was hospitalized with shingles on Thursday and amid Sen. John Fetterman’s (D-Penn.) ongoing treatment for clinical depression.

On Thursday, Feinstein, 89, said she was hospitalized with the virus and won’t return until “later this month,” while Fetterman, 53, was hospitalized at Walter Reed National Military Medical Center to treat clinical depression last month. It’s not clear when Fetterman will be released.

Two other senators this week missed votes, including Sen. Jeff Merkley (D-Ore.) and Sen. Mike Crapo (R-Ind.) Merkeley said in a statement that he is in Oregon to deal with a “family matter,” while Crapo reportedly is suffering from illness.

Because of absences this week, the Senate is deadlocked at 48–48, forcing Vice President Kamala Harris to cast tie-breaking votes for Democrats. When Crapo and Merkley return, the Senate will be tied at 49–49.

With no time-table provided for either Fetterman’s or Feinstein’s respective returns to the Senate, some analysts say that Democrats could face problems when trying to confirm President Joe Biden’s nominees.

This week, the Senate voted 49–48 in favor of one of Biden’s judicial picks, Margaret Guzman, and also voted 49–48 to confirm Araceli Martinez-Olguin to serve as a federal judge in the Northern District of California.

“Slim majorities are always challenging, but especially so in today’s Senate,” Sarah Binder, political science professor at George Washington University’s Columbian College of Arts and Science, told Newsweek on Thursday. “There are not many legislative measures on tap in the Senate, but Democrats will feel the pinch of a tied Senate whenever they try to confirm a controversial nominee.”

“In those cases, Democrats will need Vice President Harris back in the chair to break a tied vote to cut off debate on a confirmation vote,” Binder added. “That might slightly slow down Democrats and encourage them to focus on nominees who have some support from across the aisle.”

In an interview with Fox News, strategist Doug Heye said that “the danger of having such a small majority is that one or two illnesses can bring things to a halt,” noting the White House “has been aggressive and effective on judicial nominees, but that’s all on hold for now.”

https://www.zerohedge.com/political/feinstein-fetterman-hospitalizations-may-mean-trouble-democrats

Youth overweight a risk factor for blood clots as adult

 Being overweight in childhood and in early adulthood are discrete risk factors for blood clots later in life, a University of Gothenburg study shows. The study is based on the early BMI history of more than 37,000 men and information about their thrombi, if any, in adulthood.

The association between obesity and blood clots is already established. However, to date it has been unclear how much influence a raised BMI in childhood and puberty exerts. The purpose of the study was to clarify the links between BMI in early life and subsequent thrombi.

Thrombi usually arise in the legs, often starting in a blood vessel in the calf. Swelling, pain and redness are common symptoms. Treated early, clots are seldom dangerous. However, if one breaks loose, is borne to the lungs in the bloodstream, and adheres to the vessel wall there, the resulting "pulmonary embolism" may be life-threatening.

The present study comprises 37,672 men in Sweden, born between 1945 and 1961. It is based on information about height, weight, and BMI from the men's records, first from school health care services (at the age of 8 years) and, second, from medical examinations on enrollment in the Armed Services (at age 20), along with register data on any blood clots up to age 62 on average.

Distinctly elevated thrombus risk

It emerges from the results, now published in the Journal of Internal Medicine, that BMI at both ages 8 and 20, independently of each other, can be linked to venous blood clots. These may occur in, for example, the leg (deep vein thrombosis, DVT) or the lung (pulmonary embolism).

In adulthood, two groups were found to be at a significantly increased risk of venous thrombi. The first was individuals who had been overweight both as children and as young adults, while the second was composed of those whose weight in childhood was normal and who became overweight only in early adulthood.

Moreover, being overweight in both childhood and young adulthood was found to raise the risk of arterial thrombi -- that is, clots resulting from constricted blood vessels with fatty deposits and inflammation. Since there were few cases of arterial blood clots in the study, however, further studies are needed to confirm these findings. All comparisons in the study were made with the control group, whose weight was normal at both 8 and 20 years of age.

Overweight in puberty an important factor

The first and corresponding author of the study is Lina Lilja, a doctoral student at Sahlgrenska Academy, University of Gothenburg, and pediatrician. At the time of the study, she worked at the Kungshöjd pediatric clinic in Gothenburg. Today, she is a senior physician in child health care in Region Västra Götaland.

"Our study shows that both overweight in childhood and overweight in young adulthood increase the risk of venous blood clots later in life. The latter, overweight when the men were young adults, proved to be a more influential factor than overweight when they were children," Lilja notes.

Professor and senior physician Claes Ohlsson and associate professor and senior physician Jenny Kindblom, both of Sahlgrenska Academy at the University of Gothenburg and Sahlgrenska University Hospital, were senior authors of the study.

"Obesity and overweight during puberty seem to have a marked impact on a person´s future risks of venous thrombi," Kindblom concludes.

The study includes data from the BMI Epidemiology Study (BEST) in Gothenburg, a population study, and from Swedish national registers.

Journal Reference:

1. Lina Lilja, Maria Bygdell, Jari Martikainen, Annika Rosengren, Jenny M. Kindblom, Claes Ohlsson. Overweight in childhood and young adulthood increases the risk for adult thromboembolic events. Journal of Internal Medicine, 2023; DOI: 10.1111/joim.13617

https://www.sciencedaily.com/releases/2023/03/230302093408.htm

Coastal water pollution transfers to the air

 New research led by Scripps Institution of Oceanography at UC San Diego has confirmed that coastal water pollution transfers to the atmosphere in sea spray aerosol, which can reach people beyond just beachgoers, surfers, and swimmers.

Rainfall in the US-Mexico border region causes complications for wastewater treatment and results in untreated sewage being diverted into the Tijuana River and flowing into the ocean in south Imperial Beach. This input of contaminated water has caused chronic coastal water pollution in Imperial Beach for decades. New research shows that sewage-polluted coastal waters transfer to the atmosphere in sea spray aerosol formed by breaking waves and bursting bubbles. Sea spray aerosol contains bacteria, viruses, and chemical compounds from the seawater.

The researchers report their findings March 2 in the journal Environmental Science & Technology. The study appears in the midst of a winter in which an estimated 13 billion gallons of sewage-polluted waters have entered the ocean via the Tijuana River, according to lead researcher Kim Prather, a Distinguished Chair in Atmospheric Chemistry, and Distinguished Professor at Scripps Oceanography and UC San Diego's Department of Chemistry and Biochemistry. She also serves as the founding director of the NSF Center for Aerosol Impacts on Chemistry of the Environment (CAICE).

"We've shown that up to three-quarters of the bacteria that you breathe in at Imperial Beach are coming from aerosolization of raw sewage in the surf zone," said Prather. "Coastal water pollution has been traditionally considered just a waterborne problem. People worry about swimming and surfing in it but not about breathing it in, even though the aerosols can travel long distances and expose many more people than those just at the beach or in the water."

The team sampled coastal aerosols at Imperial Beach and water from the Tijuana River between January and May 2019. Then they used DNA sequencing and mass spectrometry to link bacteria and chemical compounds in coastal aerosol back to the sewage-polluted Tijuana River flowing into coastal waters. Aerosols from the ocean were found to contain bacteria and chemicals originating from the Tijuana River. Now the team is conducting follow-up research attempting to detect viruses and other airborne pathogens.

Prather and colleagues caution that the work does not mean people are getting sick from sewage in sea spray aerosol. Most bacteria and viruses are harmless and the presence of bacteria in sea spray aerosol does not automatically mean that microbes -- pathogenic or otherwise -- become airborne. Infectivity, exposure levels, and other factors that determine risk need further investigation, the authors said.

This study involved a collaboration among three different research groups -- led by Prather in collaboration with UC San Diego School of Medicine and Jacobs School of Engineering researcher Rob Knight, and Pieter Dorrestein of the UC San Diego Skaggs School of Pharmacy and Pharmaceutical Science, both affiliated with the Department of Pediatrics -- to study the potential links between bacteria and chemicals in sea spray aerosol with sewage in the Tijuana River.

"This research demonstrates that coastal communities are exposed to coastal water pollution even without entering polluted waters," said lead author Matthew Pendergraft, a recent graduate from Scripps Oceanography who obtained his PhD under the guidance of Prather. "More research is necessary to determine the level of risk posed to the public by aerosolized coastal water pollution. These findings provide further justification for prioritizing cleaning up coastal waters."

Additional funding to further investigate the conditions that lead to aerosolization of pollutants and pathogens, how far they travel, and potential public health ramifications has been secured by Congressman Scott Peters (CA-50) in the Fiscal Year (FY) 2023 Omnibus spending bill.

Besides Prather, Pendergraft, Knight and Dorrestein, the research team included Daniel Petras and Clare Morris from Scripps Oceanography; Pedro Beldá-Ferre, MacKenzie Bryant, Tara Schwartz, Gail Ackermann, and Greg Humphrey from the UC San Diego School of Medicine; Brock Mitts from UC San Diego's Department of Chemistry and Biochemistry; Allegra Aron from the UC San Diego Skaggs School of Pharmacy and Pharmaceutical Science; and independent researcher Ethan Kaandorp. The study was funded by UC San Diego's Understanding and Protecting the Planet (UPP) initiative and the German Research Foundation.

Journal Reference:

1. Matthew A. Pendergraft, Pedro Belda-Ferre, Daniel Petras, Clare K. Morris, Brock A. Mitts, Allegra T. Aron, MacKenzie Bryant, Tara Schwartz, Gail Ackermann, Greg Humphrey, Ethan Kaandorp, Pieter C. Dorrestein, Rob Knight, Kimberly A. Prather. Bacterial and Chemical Evidence of Coastal Water Pollution from the Tijuana River in Sea Spray Aerosol. Environmental Science & Technology, 2023; DOI: 10.1021/acs.est.2c02312

https://www.sciencedaily.com/releases/2023/03/230302114202.htm