English articles, Neurociencias, Noticias y artículos

Don’t underestimate the power of basic research. The neuronal and molecular mechanisms of sensory signaling. Una colaboración para el congreso de la Society for Neuroscience.

Hace unos días tuve la fortuna de asistir al congreso de la Society for Neuroscience (SfN) famoso por ser una de las reuniones científicas más importantes y grandes a nivel mundial (>30,000 asistentes). Ahí pude participar como uno de los 10 bloggers oficiales del congreso, les comparto en esta entrada uno de los textos escritos para la plataforma de Neuronline 

“Sensory transduction allow us to make sense of the complex world we are immersed in. Vision, hearing, olfaction, touch, nociception, although extremely complex all are biological adaptations of the same principle: detect physical/chemical stimuli and encode it in a signal that can be used by the system. With this in mind, it is not surprising at all that a line to attend the lecture “Start Making Sense: Neuronal and Molecular Mechanisms of Sensory Signaling” started 30 minutes prior the start of the talk. The lecturer, Dr. Piali Sengupta from Brandeis University, study the mechanisms of chemo and thermosensation in C. elegans with the ultimate goal of explaining how does sensory neurons in the periphery code specific stimuli.

I need to say that I don’t work with C. elegans, so it was surprising to me to learn that with around 60 ciliated sensory neurons C. elegans can sense and respond to a variety of stimuli such as the produced by chemicals, temperature, odorants and pheromones. The behaviors showed by C. elegans are, in words of Dr. Sengupta, extremely robust and complex, but quantifiable even distinguishable at high resolution (subdivisions of a particular behavior). Moreover, it is possible to differentiate any single neuron anatomically and morphologically. Finally, one can identify specific sensory molecules by using forward and reverse genetic approaches.

Studying C. elegans behaviors evoked by different stimuli, and the changes induced by the mutations of different genes represent a powerful tool to understand the basics of sensory systems. By using this logic Dr. Sengupta discovered and published in 1996 that the odr-10 gene encode a receptor for the odorant diacetyl but not for other odorants. But this was only the beginning, Odr-10 protein is localized in sensory cilia, but the architecture of ciliary processes is very complex and can vary a lot, think about the differences between a mammalian airway epithelial cell and rod photoreceptor. How does the neuronal sensory properties are shaped by the architecture of their sensory endings? It is a puzzling question that Dr. Sengupta is addressing right now. But as with other complex and sometimes perplexing scientific puzzles may be the answer lie in carefully observe and study a simple but invaluable organism using it as a model system for systems neuroscience.

I want to end this brief article with the words of Dr. Sengupta: Don’t underestimate the power of basic research.”

¿Interesante? Quizá quieras ver una ponencia de la Dra. Sengupta disponible en youtube

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English articles, Neurotransmisores, Noticias y artículos, Sin categoría, Videos y enseñanza.

El Premio Nobel al ciclo circadiano. Una colaboración con Ted-Ed.

Ha sido anunciado que el premio Nobel de medicina de este año va para los doctores Jeffrey C. Hall, Michael Rosbash y Michael W. Young, por sus descubrimientos de los mecanismos moleculares detrás del ciclo circadiano.

En este video hecho en colaboración con Ted-Ed les compartimos una explicación simplificada (y ahora con subtítulos en español) de este mecanismo, esperando les sea interesante.

Si gustan aquí dejamos nuestra otra colaboración con Ted Ed: ¿Qué sucede en nuestro cerebro cuando nos sentimos mal? Una colaboración con Ted-Ed.

 

Dolor, English articles, Noticias y artículos

Un nuevo papel de la hormona del crecimiento en el dolor neonatal.

Recientemente publicamos en la revista PAIN reports un análisis del artículo: Growth hormone regulates the sensitization of developing peripheral nociceptors during cutaneous inflammation del grupo del investigador Michael P Jankowski.

Los invitamos a leer este comentario en el cuál analizamos cómo la inflamación neonatal puede reducir los niveles de hormona del crecimiento y cómo sustituir farmacológicamente esta última puede prevenir la aparición de dolor.

El artículo se puede bajar de manera gratuita en la siguiente liga: PAIN Reports

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English articles, Videos y enseñanza.

¿Cómo sabe nuestro cuerpo qué hora es? Colaboración con Ted-Ed

¿Te has preguntado por qué siempre te da hambre o sueño a la misma hora? o ¿cómo es que puedes predecir cuándo el semáforo cambiará de color? Hoy en una colaboración con Ted-Ed les presentamos las respuestas

Y si quieres ver nuestro video anterior con Ted Ed te lo dejamos aquí: ¿Qué sucede en nuestro cerebro cuando nos sentimos mal? Una colaboración con Ted-Ed.

English articles, Neurotransmisores, Videos y enseñanza.

¿Qué sucede en nuestro cerebro cuando nos sentimos mal? Una colaboración con Ted-Ed.

El día de hoy compartimos una colaboración con Ted-Ed en donde hablamos de los cambios que sufre el cerebro cuando estamos enfermos, en breve se agregarán subtítulos en español.

“It starts with a tickle in your throat that becomes a cough. Your muscles begin to ache, you grow irritable, and you lose your appetite. It’s official: you’ve got the flu. It’s logical to assume that this miserable medley of symptoms is the result of the infection coursing through your body — but is that really the case? Marco A. Sotomayor explains what’s actually making you feel sick.

Lesson by Marco A. Sotomayor, animation by Henrik Malmgren.”

 

English articles, Neurotransmisores, Videos y enseñanza.

GABA and your brain’s “off”button

Continuing with neurotransmitters now we review the main inhibitory neurotransmitter, gamma amino butiric acid a.k.a. GABA, we check out it’s physiology and pharmacology.

Want to know more about other neurotransmitters? Check this out: The King of Neurotransmitters: Glutamate

English articles, Noticias y artículos

New Frontiers in Depression

Depression is a terrible disease, according to the WHO approximately 350 million people from all ages has to live with it, it is the leading cause of disability worldwide and in severe cases it leads to suicide.

Despite the advances in the field and the availability of a range of antidepressants, still a number of patients have refractory depression, this can partly be explained due to our lack of a complete understanding of this disease, however new research into brain-immune communication could be the key we were missing.

We have all experienced the torment caused by an infection, we feel terrible, everything aches and hurts us, we are cranky, downhearted, we’re never hungry and we are really sleepy, but why do we feel like this? And what does it has to do with depression?

When something activates our immune system, like an infection, as a part of the response a group of glycoproteins called cytokines are released, these affect all of the cells around them in different ways, they can increase the activity of other immune cells to increase their capacity to phagocytize and destroy harmful agents, they can also prepare other cells to endure damage, secrete hormones and now we know they also change the way our brain works.

So to alter brain function cytokines must reach it first, but as we have reviewed in prior posts the blood-brain barrier is a problem for anything in the periphery that might need to do something in the brain, so to surpass this cytokines have 4 main routes to reach the brain:

  1. Citokines activate the vagus nerve, which sends the signal through the solitary tract nucleus in the medulla oblongata, modifying the activity of this area.
  2. The circumventricular organs (area postrema, subfornical organ, organum vasculosum laminae terminalis, choroid plexus) lack a traditional blood-brain barrier, allowing them to sense citokines and respond releasing cytokines to the brain.
  3. The blood-brain barrier has specialized transporters to some cytokines, which allows them to pass a certain quantity.
  4. A number of brain venules present a large number of macrophages and endothelial cells which upon cytokine activation secrete an other transmitter called prostaglandin E towards the brain.

This signals allow the brain to create an image of the immune’s system activity so it generates an adequate response, all of the manifestations that ensue are calles sickness behavior, that includes a heightened pain perception, fatigue, hypersomnia, lack of appetite, irritability and of great importance anhedonia, anxiety and depression.

When Smith in the 90s saw these manifestations, he proposed the “macrophage theory of depression”, he also found that depressed patients had an increased level of inflammatory markers (acute phase proteins) along with an increase in the hypothalamus-hypophysis-adrenal gland axis.

Other experiments supported this view, for example patients that received IL-2 or INF α, inflammatory mediators used in the treatment of hepatitis C and melanoma, developed major depressive disorder, the pretreatment with an antidepressant like paroxetine prevented the depressive effect of these mediators.

The mechanism through which inflammation generates the sickness behavior is still elusive, however a number of mechanisms seem to play a role. When macrophages in the periphery, or microglial cells in the brain are activated with cytokines they avidly take tryptophan and metabolize it to a compound named kynurenine, this process has 2 important outcomes, firstly there is a tryptophan depletion and since it is serotonin’s precursor this important neurotransmitter is also depleted, on the other hand kynurenine by itself can block the activity or release of other neurotransmitters like glutamate and dopamine.

Other proposed mechanisms are the hypothalamus-hypophysis-adrenal hyperactivity with the consequent excess of CRH and glucocorticoids, which are known to cause depression and even psicosis.

Inflammation can also inactivate tetrahydrobipterin, an essential cofactor in the synthesis of serotonin, melatonin, dopamine, noradrenaline and nitric oxide.

The discoveries in this field of the neurosciences has important repercussions, for example in the treatment of depression that is refractory to current therapy, for example in patients with depression accompanied with high inflammatory markers in blood, the addition of aspirin or a COX 2 inhibitor like celecoxib can lead to an important recovery, the use of antibodies that block cytokines has also shown promise, drugs like etanercept can also help alleviate depression in a subset of patients.

The research in neuro-immune interactions has shown a lot of promise in a number of pathologies and depression could be next, offering hope to patients with severe refractory depression, and maybe later even diseases like anxiety, schizophrenia and autism, that we will cover in further articles.

 

OMS depresión: http://www.who.int/mediacentre/factsheets/fs369/en/

Dantzer, R., Connor, J. C. O., Freund, G. G., Johnson, R. W., & Kelley, K. W. (2010). NIH Public Access, 9(1), 46–56. http://doi.org/10.1038/nrn2297.From

Smith RS. The macrophage theory of depression. Med Hypotheses 1991;35:298–306. [PubMed: 1943879]

Berk, M., Dean, O., Drexhage, H., McNeil, J. J., Moylan, S., O’Neil, A., … Maes, M. (2013). Aspirin: a review of its neurobiological properties and therapeutic potential for mental illness. BMC Medicine, 11(1), 74. http://doi.org/10.1186/1741-7015-11-74

Muller N, et al. The cyclooxygenase-2 inhibitor celecoxib has therapeutic effects in major depression: results of a double-blind, randomized, placebo controlled, add-on pilot study to reboxetine. Mol Psychiatry 2006;11:680–684. [PubMed: 16491133]

Tyring S, et al. Etanercept and clinical outcomes, fatigue, and depression in psoriasis: double-blind placebo-controlled randomised phase III trial. Lancet 2006;367:29–35. [PubMed: 16399150]

English articles

The origin of intelligence, is it acquired or is it inherited?

Academic

The origin of intelligence has been a historical debate, is it acquired or is it inherited? Let us just think about the Bohr family. Christian Bohr was a successful physician in Edinburgh, his son, Niehls Bohr, was a Nobel Laureate in Physics, and his grandson, Aage Bohr also won a Nobel Prize in Physics. So, here is the question: Was geniality printed in their genes or did they live in an enriching environment that facilitated their academic achievements?

Nowadays it is hard to deny that academic achievement has become a major goal in society; indeed, academic achievement has been associated to better health, life expectancy and career success. And, as with intelligence, academic achievement appears to depend, at least partially, on the subject’s genetics.

On the other hand, the role of a common environment (family, income, school, educational system, etc) is more difficult to explain. It is an everyday observation that children in the same school, even in the same classroom exhibit higher, or lower, performance that their peers.

An article addressing this question of genetic versus environmental influences on academic achievement has been recently published by a research group from King’s College London (United Kingdom). This large study investigated the academic outcomes of more than 12,000 twins that took their GCSE* (General certificate of Secondary Education – an important test performed at age 16) and analyzed if these outcomes were more related to inheritance or environment.

The results were interesting. The heritability had a correlation of around 54 to 65% with the GCSE outcomes, while environment only had one of 14 to 21%. Heritability had an even greater impact on intelligence, with a correlation of 56%. On the contrary, environment factors were only 5% correlated.

But here is a problem: twins are often raised in the same environment, so to eliminate this factor, the researchers also used a new technique called GCTA (Genome-Wide Complex Trait Analysis). The GCTA is a genetic tool that enables us to study the effect of genetic influence of unrelated individuals**. In this case in academic performance. After the exclusion of 1 out of every twin, a correlation between the genetic similarity of unrelated individuals and the academic performance was addressed again. The new results supported the previous findings in wins, even using the new GCTA technique, a genetic correlation was found in both intelligence and academic achievement in unrelated individuals.

So, it might appear as if all is lost and that our genes will always write our destiny, but do not despair. The researchers explain that the negligible effect of environment may be due to the highly standardized curriculum in the United Kingdom, a country with a strongly centralized educational system. In other studies the effect of environment, health, family, educational system, etc. have proven to be more important when compared with the present study.

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* The GCSE evaluates different academic subjects such as mathematics, science, English, art, humanities and second language learning.
** GCTA search for thousands of single nucleotide polymorphisms (SNPs) to calculate the phenotypic variance.

Reference:
Rimfeld K, Kovas Y, Dale PS, Plomin R. Pleiotropy across academic subjects at the end of compulsory education. Sci Rep. 2015 Jul 23;5:11713. doi: 10.1038/srep11713.