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2015 ended on a high note. December was full of good news. Last month’s best discoveries provide a handful of new promising therapies, including new evidence for a beneficial effect of exercise on the brain. Still, not even the holiday spirit managed to keep us away from some bad news. Here are the best and worst findings I came across in December.
Cannabidiol for the treatment of epilepsy
Many patients with epilepsy are unaffected by pharmacological treatment. This treatment-resistant form of epilepsy is associated with severe disability and a higher mortality rate. In recent years, alternative treatments based on cannabis use have been showing some promising effects, but clinical studies are still lacking.
In December, The Lancet Neurology presented a study that aimed at determining if the addition of cannabidiol (CBD), one of the active compounds found in cannabis, to existing anti-epileptic treatment regimens would be safe, well-tolerated, and effective in children and young adults with treatment-resistant epilepsy. The results showed that CBD was indeed safe and effective in children and young adults with highly treatment-resistant forms of epilepsy, being able to reduce seizure frequency.
The effect of aerobic exercise on memory
In the last years, evidence supporting a beneficial effect of exercise on cognition has been accumulating. Aerobic exercise prevents cognitive decline, particularly affecting learning and memory. Research has suggested that this effect may be due to changes in the hippocampus, a brain region with a key role in learning and memory. Animal studies have also shown that aerobic exercise increases the production of growth factors acting on the brain.
A study published in NeuroImage addressed this issue by testing the association between cardio-respiratory fitness and the volume of the hippocampus and the entorhinal cortex, another key region in memory processing. Results showed that there was indeed a positive link between entorhinal cortex volume, cardio-respiratory fitness and memory performance, providing evidence for another target of the cerebral effects of aerobic exercise and fitness.
Overcoming obstacles in Parkinson’s disease therapy
A couple of years ago, research had shown that the administration of a molecule named GM1 ganglioside had neuroprotective and neuroregenerative effects in Parkinson’s disease, both in animal models and in patients. However, a number of obstacles have hampered its therapeutic application. Therefore, a study published in PLoS ONE aimed at finding an alternative approach to the systemic administration of GM1 to enhance its levels in the brain.
The authors applied an enzyme named sialidade to convert endogenous molecules into GM1 and tested the neuroprotective potential of this approach. Results showed that this strategy is effective in mice, increasing the GM1 levels in the brain and showing a neuroprotective effect in Parkinson’s disease. If applicable to humans, this may be a promising therapy.
A double function for an antidepressant drug
Depression has been associated with increased chronic inflammation. This is most likely due to the close association between depression and stress. Stress can stimulate the immune system and induce a pro-inflammatory response that, with time, brings about a variety of health issues.
A study published in the Journal of Psychiatric Research examined whether treatment with the antidepressant drug escitalopram could decrease inflammation in patients with major depressive disorder. The blood levels of neurotoxic substances secreted by the immune system were measured and it was found that their levels were higher in the depressed patients. Treatment with escitalopram decreased the levels of two of those neurotoxic compounds showing an additional beneficial effect of this antidepressant compound.
Neuroprotection following global cerebral ischemia
Global cerebral ischemia is one of the immediate consequences of cardiac arrest. As soon as the heart stops beating, oxygen delivery to the brain via the blood is impaired, and oxidative damage to the brain ensues, which can potentially lead to cognitive impairment.
With the goal of preventing such consequences of cardiac arrest, a new neuroprotective peptide that can stimulate antioxidant and cell-defense mechanisms in the brain has been developed, as reported in The Journal of Neuroscience. This work showed that this peptide, named DEETGE-CAL-Tat, allows the activation of molecular mechanisms of injury response in an animal model of global cerebral ischemia. It induced the expression of antioxidant and neuroprotective genes, reduced oxidative stress, and protected cognitive function after global cerebral ischemia. Interestingly, these effects were not observed in control animals, showing that they were injury-specific.
A link between stress and memory loss
NG2 glia is a type of glial cell better known for being progenitors of myelinating glial cells. A few new functions have been discovered for these cells, having been shown that NG2 glia may also have other important roles in maintaining a balanced central nervous system.
A new study published in Neuron showed that the ablation of NG2 glia in the prefrontal cortex of the adult brain of mice can cause depressive-like behaviors. Importantly, the study also showed that chronic social stress can cause a decrease in the density of NG2 glial cells in areas of the brain that play a key role in major depressive disorder. This study therefore establishes a link between stress-induced cell loss in the brain and the development of depressive symptoms, highlighting the impact of stress on mental health.
Deficient iron intake affects prenatal development
Iron is an essential mineral with numerous health functions in our body. Insufficient exposure to iron during prenatal development is known to affect motor and cognitive development. To better determine the link between iron exposure and brain development, work published in Pediatric Research assessed for the first time the effect of daily iron intake during the third pregnancy trimester in healthy pregnant adolescents. It was shown that iron intake affects the organization of newborns’ brain tissue.
Higher maternal prenatal iron intake was associated with greater complexity in brain tissue, indicating greater brain maturity; lower intake, on the other hand, was associated with delayed structural development of gray matter in the brain. This study thereby highlights the impact of diet, namely iron intake, on infant brain development.
Human herpesvirus can directly infect neurons
Human herpesvirus 4 (HHV4), also known as Epstein-Barr virus (EBV) is associated with a number of human cancers, along with various neurological diseases. Despite the link with these neurological conditions, the possibility that EBV and Kaposi’s sarcoma-associated herpesvirus (KSHV) can directly infect neurons has been disregarded.
But a study published in mBio has, for the first time, shown that both EBV and KSHV can directly infect neuronal cells. This work also showed that the infection of neurons by EBV and KSHV is efficient and productive, with the viruses being able to replicate in infected neurons in vitro. These findings indicate that neuronal infection with EBV or KSHV may be a key contributor to the pathogenesis of different neurological diseases, namely multiple sclerosis, primary central nervous system lymphoma, and Alzheimer’s disease, which have been associated to these viruses.
A genetic background for congenital heart disease and neurodevelopmental delays
Children with congenital heart disease are known to be at a higher risk of neurodevelopmental disorders, often showing cognitive impairments, as well as diminished language and social skills. The reason for this pattern remained unknown, but it was hypothesized that it could be due to an insufficient delivery of nutrients and oxygen to the brain, or to a common genetic background causing both the cardiac and neurological deficits.
The answer to this question was exactly what the Pediatric Cardiovascular Genetics Consortium sought in a study published in Science. The consortium performed a genetic analysis of over 1,200 children and their parents and found that children having both congenital heart disease and neurodevelopmental disorders share genetic mutations that compromise the normal development of the heart and the brain. These results underline the likelihood of children with congenital heart disease also having neurological deficits, while also raising awareness for the need for an early therapeutic intervention.
Chemotherapy-induced cognitive impairments
Chemotherapy exposure is a known risk factor for cancer-related cognitive impairments. Chemotherapies based on anthracycline have been shown to be associated with cognitive impairment and brain changes in clinical studies. Therefore, to better understand the contribution of anthracycline to chemotherapy-associated cognitive impairments, research published in JAMA Oncology aimed at directly comparing the effects of anthracycline and nonanthracycline chemotherapy on cognitive function.
Using data primary breast cancer survivors who had either received anthracycline or nonanthracycline-based chemotherapy or no chemotherapy at all, it was found that the anthracycline group demonstrated significantly lower verbal memory performance. These results therefore indicate that anthracycline may have a greater negative impact on cognitive function and brain connectivity than nonanthracycline treatment, although some nonspecific effects were also observed with the latter.
Birey F, Kloc M, Chavali M, Hussein I, Wilson M, Christoffel DJ, Chen T, Frohman MA, Robinson JK, Russo SJ, Maffei A, & Aguirre A (2015). Genetic and Stress-Induced Loss of NG2 Glia Triggers Emergence of Depressive-like Behaviors through Reduced Secretion of FGF2. Neuron, 88 (5), 941-56 PMID: 26606998
Devinsky O, Marsh E, Friedman D, Thiele E, Laux L, Sullivan J, Miller I, Flamini R, Wilfong A, Filloux F, Wong M, Tilton N, Bruno P, Bluvstein J, Hedlund J, Kamens R, Maclean J, Nangia S, Singhal NS, Wilson CA, Patel A, & Cilio MR (2015). Cannabidiol in patients with treatment-resistant epilepsy: an open-label interventional trial. The Lancet. Neurology PMID: 26724101
Halaris A, Myint AM, Savant V, Meresh E, Lim E, Guillemin G, Hoppensteadt D, Fareed J, & Sinacore J (2015). Does escitalopram reduce neurotoxicity in major depression? Journal of psychiatric research, 66-67, 118-26 PMID: 26009299
Homsy, J., Zaidi, S., Shen, Y., Ware, J., Samocha, K., Karczewski, K., DePalma, S., McKean, D., Wakimoto, H., Gorham, J., Jin, S., Deanfield, J., Giardini, A., Porter, G., Kim, R., Bilguvar, K., Lopez-Giraldez, F., Tikhonova, I., Mane, S., Romano-Adesman, A., Qi, H., Vardarajan, B., Ma, L., Daly, M., Roberts, A., Russell, M., Mital, S., Newburger, J., Gaynor, J., Breitbart, R., Iossifov, I., Ronemus, M., Sanders, S., Kaltman, J., Seidman, J., Brueckner, M., Gelb, B., Goldmuntz, E., Lifton, R., Seidman, C., & Chung, W. (2015). De novo mutations in congenital heart disease with neurodevelopmental and other congenital anomalies Science, 350 (6265), 1262-1266 DOI: 10.1126/science.aac9396
Jha HC, Mehta D, Lu J, El-Naccache D, Shukla SK, Kovacsics C, Kolson D, & Robertson ES (2015). Gammaherpesvirus Infection of Human Neuronal Cells. mBio, 6 (6) PMID: 26628726
Kesler SR, & Blayney DW (2015). Neurotoxic Effects of Anthracycline- vs Nonanthracycline-Based Chemotherapy on Cognition in Breast Cancer Survivors. JAMA oncology, 1-8 PMID: 26633037
Monk C, Georgieff MK, Xu D, Hao X, Bansal R, Gustafsson H, Spicer J, & Peterson BS (2015). Maternal prenatal iron status and tissue organization in the neonatal brain. Pediatric research PMID: 26599151
Schneider JS, Seyfried TN, Choi HS, & Kidd SK (2015). Intraventricular Sialidase Administration Enhances GM1 Ganglioside Expression and Is Partially Neuroprotective in a Mouse Model of Parkinson’s Disease. PloS one, 10 (12) PMID: 26629687
Tu J, Zhang X, Zhu Y, Dai Y, Li N, Yang F, Zhang Q, Brann DW, & Wang R (2015). Cell-Permeable Peptide Targeting the Nrf2-Keap1 Interaction: A Potential Novel Therapy for Global Cerebral Ischemia. The Journal of neuroscience : the official journal of the Society for Neuroscience, 35 (44), 14727-39 PMID: 26538645
Whiteman AS, Young DE, Budson AE, Stern CE, & Schon K (2015). Entorhinal volume, aerobic fitness, and recognition memory in healthy young adults: A voxel-based morphometry study. NeuroImage, 126, 229-238 PMID: 26631814
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