In June, the beneficial effects of exercise were on the spotlight again, along with a few potentially effective new therapies. On the down side, there were a number of studies highlighting the negative side-effects of commonly used drugs. Here is the best and worst news of June.

THE BEST

Consensus on the effect of physical activity on children and youth

In April 2016, a multi-disciplinary group of 24 researchers from 8 countries gathered in Denmark to discuss the scientific evidence on the effect of physical activity in children and youth. This conference led to the publication of a consensus statement that was made available in June in the British Journal of Sports Medicine. The statement was made up of 21 items divided into 4 themes addressing the effect of physical activity on fitness and health; cognitive functioning; engagement, motivation and psychological well-being; and social inclusion.

Overall, it reinforces that physical activity is great, which is always worth underlining. The statement can be read here.

Dietary supplement mix can delay aging

There are many neurological and neurodegenerative diseases that are driven by inflammation and oxidation. These processes are also responsible for aging and the associated cognitive decline. Dietary supplements containing natural ingredients with strong anti-inflammatory and anti-oxidant proprieties may therefore be a great alternative to drugs in the treatment of neurological conditions and in delaying cognitive aging.

A study published in Environmental and Molecular Mutagenesis therefore assessed the effect of a multi-ingredient dietary supplement on a mouse model of accelerated aging that is characterized by chronic oxidative stress, increased inflammation, severe cognitive decline, physical deterioration, and reduced longevity. It was shown that the supplement, containing around 30 ingredients, could reverse brain cell loss and cognitive decline, and increase sensory and motor function in aged mice, highlighting the therapeutic potential of dietary approaches.

A new approach to counteract the negative effects of general anesthesia

General anesthesia can have undesired cognitive and behavioral side-effects, particularly in children, whose brain is still developing. Effective preventive therapies are still lacking. A new study published in Science Translational Medicine has shown that ketamine anesthesia is responsible for a significant reduction in neuronal activity during the post-anesthesia recovery period. Since ketamine acts mainly by inhibiting glutamate receptors, the study tested the effect, in neonatal mice, of a drug designed to potentiate the activity of AMPA receptors (a type of glutamate receptor).

Administration of the drug during emergence from anesthesia led to an increase in neuronal activity, thereby counterbalancing the effects of ketamine. This therapeutic intervention was able to prevent the development of synaptic and motor learning deficits induced by repeated neonatal anesthesia, indicating that this may be an effective approach to reduce the detrimental effects of anesthesia on brain development.

A new drug delivery method for brain injuries

One of the main difficulties in the treatment of traumatic brain injury is the delivery of drugs to the affected area in a way that is both non-invasive (not requiring surgery) and directed to the injured area, minimizing potential undesired side-effects.

In June, Nature Communications published an article reporting a new drug delivery method that can specifically target injured areas of the brain. The authors identified a specific peptide that selectively binds to molecules that are overproduced following injury in the brains of both mice and humans. Using nanoparticles coated with this peptide allowed a targeted delivery of drugs by a simple intravenous administration. These findings may allow for significant improvements in the treatment of brain injuries.

Neural stem cells successfully applied to aged brains

New potential applications of neural stem cells keep appearing. A new study published in Stem Cells Translational Medicine adds to the list by showing that grafting neural stem cells into the hippocampus of both young and aged rats is effective and enduring, leading to the differentiation of those cells and to the formation of new neurons.

These results are important because they show that an aged brain retains the ability to allow the grafting of those cells and their proliferation. This opens a new line of potential treatments for neurodegenerative diseases and age-related cognitive decline, since the hippocampus plays a key role in some of the cognitive functions that are most affected by these conditions, namely memory.

THE WORST

Serotonin reuptake inhibitors negatively affect fetal brain development

There are many drugs that can affect fetal development and that are therefore counter-indicated during pregnancy. Animal studies had already provided evidence of a potential negative effect of antidepressant serotonin reuptake inhibitors (SRI) on brain development. Now, the journal Cerebral Cortex published a new study that used electroencephalography (EEG) to study if similar effects are also observed in newborn humans.

EEG recordings showed that there are indeed a number of developmental brain structural deficits in newborns exposed to SRIs during fetal development.

Acetaminophen during pregnancy may affect neurodevelopmental behavioral outcomes

Another drug whose effect during pregnancy has been the subject of research published in June is acetaminophen, also known as paracetamol. Acetaminophen is extensively used, including during pregnancy, but its effect on fetal brain development is poorly studied.

As reported in the International Journal of Epidemiology, the offspring of women who took acetaminophen during pregnancy showed a greater number of symptoms associated with autism spectrum disorder, in a way that was dependent on the frequency of exposure. However, this effect was only observed in males. Adverse effects on attention-related outcomes were observed for both genders.

Prolonged opioid treatment increases mortality

Opioids are widely used for the treatment of pain, but they present a myriad of undesired side-effects, including cardiorespiratory deficits that may lead to death. New research published in The Journal of the American Medical Association compared the mortality of patients with chronic non-cancer pain who were prescribed either opioids or non-opioid analgesic treatment, aiming to determine if continued opioid treatment could lead to a higher risk of death.

This study determined that, when compared with anticonvulsants or cyclic antidepressants, long-acting opioids were indeed associated with significantly higher mortality.

The link between stress and epileptic seizures

Stress can increase the frequency of epileptic seizures. Research published in Science Signaling showed that stress and anxiety induce the production of a neuropeptide called corticotropin-releasing factor (CRF), which coordinates many responses to stress in the central nervous system.

But while in normal conditions CRF acts to decrease excitability in areas prone to the occurrence of seizures, in the context of epilepsy this neuropeptide acquires other functions due to changes in cellular signaling pathways, becoming a promotor of seizures. So, what would otherwise be a protective response to stress, becomes a damaging response to stress in subjects with epilepsy, explaining why stress and anxiety can increase the occurrence of seizures.

Cerebral vascular conditions as risk factors for dementia

Cerebral atherosclerosis limits the flow of blood and oxygen to the brain, therefore having the potential to negatively affect brain function. A study published in The Lancet Neurology assessed clinical data recorded between 1994 and 2015 to determine whether cerebral blood vessel diseases could increase the likelihood of developing dementia and cognitive impairment associated with Alzheimer’s disease.  

The results of this work, which included 1143 subjects, showed that cerebral atherosclerosis and arteriolosclerosis are associated with Alzheimer’s disease dementia and decreased cognitive scores. This data indicates that cerebral vascular pathologies may be a risk factor for dementia associated with Alzheimer’s disease.

References

Arvanitakis, Z., Capuano, A., Leurgans, S., Bennett, D., & Schneider, J. (2016). Relation of cerebral vessel disease to Alzheimer’s disease dementia and cognitive function in elderly people: a cross-sectional study The Lancet Neurology, 15 (9), 934-943 DOI: 10.1016/S1474-4422(16)30029-1

Avella-Garcia, C., Julvez, J., Fortuny, J., Rebordosa, C., García-Esteban, R., Galán, I., Tardón, A., Rodríguez-Bernal, C., Iñiguez, C., Andiarena, A., Santa-Marina, L., & Sunyer, J. (2016). Acetaminophen use in pregnancy and neurodevelopment: attention function and autism spectrum symptoms International Journal of Epidemiology DOI: 10.1093/ije/dyw115

Bangsbo J, Krustrup P, Duda J, Hillman C, Andersen LB, Weiss M, Williams CA, Lintunen T, Green K, Hansen PR, et al (2016). The Copenhagen Consensus Conference 2016: children, youth, and physical activity in schools and during leisure time. Br J Sports Med [Epub ahead of print] doi: 10.1136/bjsports-2016-096325

Huang, L., Cichon, J., Ninan, I., & Yang, G. (2016). Post-anesthesia AMPA receptor potentiation prevents anesthesia-induced learning and synaptic deficits Science Translational Medicine, 8 (344), 344-344 DOI: 10.1126/scitranslmed.aaf7151

Lemon, J., Aksenov, V., Samigullina, R., Aksenov, S., Rodgers, W., Rollo, C., & Boreham, D. (2016). A multi-ingredient dietary supplement abolishes large-scale brain cell loss, improves sensory function, and prevents neuronal atrophy in aging mice Environmental and Molecular Mutagenesis, 57 (5), 382-404 DOI: 10.1002/em.22019

Mann, A., Scodeller, P., Hussain, S., Joo, J., Kwon, E., Braun, G., Mölder, T., She, Z., Kotamraju, V., Ranscht, B., Krajewski, S., Teesalu, T., Bhatia, S., Sailor, M., & Ruoslahti, E. (2016). A peptide for targeted, systemic delivery of imaging and therapeutic compounds into acute brain injuries Nature Communications, 7 DOI: 10.1038/ncomms11980

Narla, C., Scidmore, T., Jeong, J., Everest, M., Chidiac, P., & Poulter, M. (2016). A switch in G protein coupling for type 1 corticotropin-releasing factor receptors promotes excitability in epileptic brains Science Signaling, 9 (432) DOI: 10.1126/scisignal.aad8676

Ray, W., Chung, C., Murray, K., Hall, K., & Stein, C. (2016). Prescription of Long-Acting Opioids and Mortality in Patients With Chronic Noncancer Pain JAMA, 315 (22) DOI: 10.1001/jama.2016.7789
Shetty AK, Hattiangady B (2016). Grafted Subventricular Zone Neural Stem Cells Display Robust Engraftment and Similar Differentiation Properties and Form New Neurogenic Niches in the Young and Aged Hippocampus. Stem Cells Transl Med [Epub ahead of print]. doi: 10.5966/sctm.2015-0270

Videman, M., Tokariev, A., Saikkonen, H., Stjerna, S., Heiskala, H., Mantere, O., & Vanhatalo, S. (2016). Newborn Brain Function Is Affected by Fetal Exposure to Maternal Serotonin Reuptake Inhibitors Cerebral Cortex DOI: 10.1093/cercor/bhw153

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