Thursday, June 25, 2020

Land of Fire and Ice

The Arctic is on fire: Siberian heat wave alarms scientists


Iceland has been referred to as the land of fire and ice. Looks like that appellation needs to be more broadly geographically based. 

Does Toxicology Testing Need Improvement?

Effects from low-level concentrations of harmful chemicals preserved in three generations of fish


I've seen related findings going back many years but all too often we rely on short term high concentration toxicology testing. Increasing evidence is finding that persistent low level exposure to various chemicals can have important health consequences for the individual. This study finds that it is not only the individual that is affected but also the following generations. It is about endocrine disruptors, molecules which impact on hormonal functions. So the result isn't that surprising because hormones are very powerful molecules which are produced in relatively small quantities. 

A Promising Breakthrough for Treating Parkinson's Disease?

One-time treatment generates new neurons, eliminates Parkinson's disease in mice


Because Parkinson's disease is very much about the loss of dopamine producing neurons the great hope has always been stem cells to create neurons which produce dopamine. In a classic example of a accidental discovery this breakthrough found that many cell types will become dopamine producing neurons. 

In this serendipitous way, the team discovered that inhibiting or deleting just a , the gene that encodes PTB, transforms several types of mouse cells directly into neurons. 

The abstract:

Nature volume 582pages550556(2020)

Parkinson’s disease is characterized by loss of dopamine neurons in the substantia nigra1. Similar to other major neurodegenerative disorders, there are no disease-modifying treatments for Parkinson’s disease. While most treatment strategies aim to prevent neuronal loss or protect vulnerable neuronal circuits, a potential alternative is to replace lost neurons to reconstruct disrupted circuits2. Here we report an efficient one-step conversion of isolated mouse and human astrocytes to functional neurons by depleting the RNA-binding protein PTB (also known as PTBP1). Applying this approach to the mouse brain, we demonstrate progressive conversion of astrocytes to new neurons that innervate into and repopulate endogenous neural circuits. Astrocytes from different brain regions are converted to different neuronal subtypes. Using a chemically induced model of Parkinson’s disease in mouse, we show conversion of midbrain astrocytes to dopaminergic neurons, which provide axons to reconstruct the nigrostriatal circuit. Notably, re-innervation of striatum is accompanied by restoration of dopamine levels and rescue of motor deficits. A similar reversal of disease phenotype is also accomplished by converting astrocytes to neurons using antisense oligonucleotides to transiently suppress PTB. These findings identify a potentially powerful and clinically feasible approach to treating neurodegeneration by replacing lost neurons.

Wednesday, June 24, 2020

Prenatal stress can cause long-term behavioral deficits in mice

Prenatal stress can cause long-term behavioral deficits in mice


Prenatal stress, especially maternal immune activation has long been strongly associated with behavioral changes in the offspring. Maternal immune activation is not just about a mild infection it typically involves a severe and persistent infection. It is a leading risk marker for schizophrenia and autism. This study goes one step further and finds that by simply blocking one molecule, CCL2, they could prevent the behavioral changes in the offspring. I'm a little suspicious of that and obviously that can't be extrapolated to human beings. Blocking CCL 2 might seem like a good idea for pregnant women experiencing stress but biological molecules typically have many different effects and we don't know what the consequences of blocking that molecule will have for the overall health of the women and the developing fetus. 

The findings suggest that the maternal microbiome or immune system could be good targets for developing preventive treatments for women who experience stress during pregnancy.
The problem though is that maternal immune activation is not enough, there is a genetic component to the emergence of these conditions. The genetic component involves some immune related genes but also involves genes relating to brain development. 


Nonetheless as a preventive strategy pregnant women should avoid potentially dangerous infections and generally manage their stress. This is one reason why I have concerns about pregnant women working in some roles where the risk of infection and high levels of psychological stress exist. I think our society has over stepped the mark on this matter and as research accumulates I hope more pregnant women, socioeconomic circumstances notwithstanding, are able to adopt the traditional approach of being nurtured through their pregnancy rather than being expected to perform as everyone else.
 

Is the USA a failing state?

Is America a ‘failing state’? How a superpower has been brought to the brink

At present it isn't a healthy state but it is hyperbolic to suggest it is a failing state. Nations go through periods of turmoil but democratic nations typically survive and adjust to the new realities. The problem for the USA is that it has a president promoting division, has handled the coronavirus pandemic in a poor fashion, and has threatened to send in the military to contain the street violence. 

The USA has a growing problem with economic inequality. The recent tax cuts only exacerbate that trend because those tax cuts support the top of the economic food chain. While unemployment is at record lows that doesn't appear to be addressing the economic inequality situation, possibly because most of those jobs are minimum wage jobs. There is some reason for optimism because wages have increased but that might be a function of various states raising the minimum wage. 

I don't think the USA is becoming a failing state but it would certainly help if the leadership adopting a more creative approach to reducing the street violence rather than just threatening to call in the military. The protestors have gone too far and at both the federal and state levels the authorities seem incapable to quell the unrest. 

Sweden's Coronavirus Strategy Failure

Public support for Sweden's controversial coronavirus strategy is plummeting


Sweden coronavirus strategy struck many as being unusual and dangerous. Initially conservatives praised Sweden for not falling prey to alarmism and sacrificing their economy to the boogeyman. Conservatives are quiet now because Sweden has paid a heavy price. It is worth noting that the Swedish government may have had no choice because the Swedish constitution doesn't allow the government to impose such onerous restrictions on personal behaviour as was adopted in many other advanced nations. 

Monday, July 15, 2013

Everybody Must Get Stoned?

This is a startling result and I have to wonder why it isn't being more widely publicised:

In the present study, we observed smaller brain weights and volumes in male macaque monkeys after 1.5–2.3 years of exposure to marijuana at plasma drug levels comparable to those in treated humans. Exposure to marijuana was associated with a similar reduction in mean fresh brain weight, as well as mean fresh weight and volume of the left cerebrum, compared to matched, placebo-exposed animals. For both drugs, the magnitude of these effects was in the range of 8–11%. The reduction seemed to be global (ie including all brain regions), but was most robust in the frontal and parietal lobes. In addition, both gray and white matter volumes appeared to be reduced to a similar degree.