By Neuronicus, 16 May 2017.
By Neuronicus, 16 May 2017.
It is April and the Northern Hemisphere is enjoying the sight and smell of blooming magnolias. Fittingly, today is the birthday of the man who described and named the genus. Charles Plumier (20 April 1646 – 20 November 1704) was a French botanist known for describing many plant genera and for preceding Linnaeus in botanical taxonomy. His (Plumier’s) taxonomy was later incorporated by Linnaeus and is still in use today.
Plumier traveled a lot as part of his job as Royal Botanist at the court of Louis XIV. Don’t envy him too much though because the monk order to which he belonged, the Minims, forced him to be a vegan, living mostly on lentil.
Among thousands of other plants described was the magnolia, a genus of gorgeous ornamental flowering trees that put out spectacularly big flowers in the Spring, usually before the leaves come out. Plumier found it in the island of Martinique and named it after Pierre Magnol, a contemporary botanist who invented the concept of family as a distinct taxonomical category.
Interestingly enough, Plumier named other plants either after famous botanists like fuchsia (Leonhard Fuchs) and lobelia (Mathias Obel) or people who helped his career as in begonia (Micheal Begon) and suriana (Josephe Donat Surian), but never after himself. I guess he took seriously the humility tenet of his order. Never fear, the botanists Joseph Pitton de Tournefort and the much more renown Carl Linnaeus named an entire genus after him: Plumeria.
Of interest to me, as a neuroscientist, is that the bark of the magnolia tree contains magnolol which is a natural ligand for the GABAA receptor.
REFERENCE: Plumier, C. (1703). Nova Plantarum Americanum Genera, Paris. http://dx.doi.org/10.5962/bhl.title.59135 FULLTEXT courtesy of the Biodiversity Heritage Library
By Neuronicus, 20 April 2017
The pineal gland held fascination since Descartes’ nefarious claim that it is the seat of the soul. There is no evidence of that; he said it might be where the soul resides because he thought the pineal gland was the only solitaire structure in the brain so it must be special. By ‘solitaire’ I mean that all other brain structures come in doublets: 2 amygdalae, 2 hippocampi, 2 thalami, 2 hemispheres etc. He was wrong about that as well, in that there are some other singletons in the brain besides the pineal, like the anterior or posterior comissure, the cerebellar vermis, some deep brainstem and medullary structures etc.
Descartes’ dualism was the only escape route the mystics at the time had from of the demanding of evidence by the budding natural philosophers later known as scientists. So when some scientists noted that some lizards have a third eye on top of their head, the mystics and, later, the conspiracy theorists went nuts. Here, see, if the soul seat is linked with the third eye, the awakening of this eye in people would surely result in heightened awareness, closeness to the Divinity, oneness with Universe and other similar rubbish that can be otherwise easily and reliably achieved by a good dollop of magic mushrooms. Cheaper, too.
Back to the lizards. Yes, you read right: some lizards and frogs have a third eye. This eye is not exactly like the other two, but it has cells sensitive to light, even if they are not perceiving light in the same way the retinal cells form the lateral eyes are. It is located on the top of the skull, so sometimes is called the parietal organ (because it’s in-between the parietal skull bones, see pic).
It is believed to be a vestigial organ, meaning that primitive vertebrates might have had it as a matter of course but it disappeared in the more evolved animals. Importantly, birds and mammals don’t have it. Not at all, not a bit, not atrophied, not able to be “awakened” no matter what your favorite “lemme see your chakras” guru says. Go on, touch your top of the skull and see if you have some peeking soft tissue there. And no, the soft tissue that babies are born with right there on the top of the skull is not a third eye; it’s a fontanelle that allows for the rapid expansion of the brain during the first year of life.
The parietal organ’s anatomical connection to the pineal gland is not surprising at all for scientists, because the pineal’s role in every single animal that has it is the regulation of some circadian rhythms by the production of melatonin. In humans, the eyes send the information to the pineal that is day or night and the pineal adjusts the melatonin production accordingly, i.e. less melatonin produced during day and more during night. The lizards’ third eye’s main role is to provide information to the pineal about the ambient light for thermoregulatory purposes.
After this long introduction, here is the point: almost twenty years ago Xiong et al. (1998) looked at how this third eye perceives light. In the human eye, light hitting the rods and cones in the retina (reception) launches a biochemical cascade (transduction) that results in seeing (coding of the stimulus in the brain). Briefly, transduction goes thusly: the photon(s) causes a special protein sensitive to light (e.g. rhodopsin) in the photoreceptor cells in the retina to split into its components (photobleaching), one of these components changes its conformation, then activates a G-protein (transducin), which then activates the enzyme phosphodiesterase (PDE), which then destroys a nucleotide called cyclic guanosine monophosphate (cGMP), which results in the closing of the cell’s ion channels, which leads to less neurotransmitter GABA released, which causes the nearby cells (bipolar cells) to release another neurotransmitter (glutamate), which increases the firing rate of another set of cells (ganglion cells) and from there to the brain we go. Phew, visual transduction IS difficult. And this is the brief version.
It turns out that the third eye retina doesn’t have all the types of cells that the normal eyes have. Specifically, it misses the bipolar, horizontal and amacrine cells, having only ganglion and photoreception cells. So how goes the phototransduction in the third eye’s retina, if at all?
Xiong et al. (1998) isolated photoreceptor cells from the third eyes of the lizard Uta stansburiana. And then they did a bunch of electrophysiological recording on those cells under different illumination and chemical conditions.
They found that the phototransduction in the third eye is different from the lateral eyes in that when they expected to see hyperpolarization of the cell, they observed depolarization instead. Also, when they expected the PDE to break down cGMP they found that PDE is inhibited thereby increasing the amount of cGMP The fact that G-protein can inhibit PDE was totally unexpected and showed a novel way of cellular signaling. Moreover, they speculate that their results can make sense only if not one, but two G-proteins with opposite actions work in tandem.
A probably dumb technical question though: the human rhodopsin takes about 30 minutes to restore itself from photobleaching. Xiong et al. (1998) let the cells adapt to dark for 10 minutes before recordings. So I wonder if the results would have been slightly different if they allowed the cell more time to adapt? But I’m not an expert in retina science, you’ve seen how difficult it is, right? Maybe the lizard proteins are different or rhodopsin adaption time has little or nothing to do with their experiments? After all, later research has shown that the third eye has its own unique opsins, like the green-sensitive parietopsin discovered by Su et al. (2006).
REFERENCE: Xiong WH, Solessio EC, & Yau KW (Sep 1998). An unusual cGMP pathway underlying depolarizing light response of the vertebrate parietal-eye photoreceptor. Nature Neuroscience, 1(5): 359-365. PMID: 10196524, DOI: 10.1038/1570. ARTICLE
Tags: whole-cell electrophysiological recordings, perforated-patch electrophysiological recording, phototransduction, rhodopsin, photoreceptor, retina, G-protein, phosphodiesterase (PDE), cyclic guanosine monophosphate (cGMP), adenylyl cyclase, 3-isobutyl-1-methyl-xanthine (IBMX), parietal eye, third eye, lizard, opsin, G-protein, Uta stansburiana
By Neuronicus, 30 March 2017
By the late 18th and beginning of 19th century, some scientists were busily investigating how animals get their colors and how do they change colour in response to the environment. They identified several types of chromatophores, i.e. cells that contain pigments. Biological pigments are called melanins (don’t confuse them with melatonin). One of these cells is the melanophore which contains black pigments, called this way in the very typical scientist unimaginative style because “melas” in Greek means black or dark and “phoros” means carrier.
A couple of these scientists, McCord & Allen (1917), thought that the pineal gland from the brain might contain some substance that might interact with the melanophores. How did they get this idea is unclear from their paper; seems like a logical outcome of their contemporaries’ discussions and experiments, though they do not explain it in detail. They hint of other experiments where various glands have been fed to amphibians and then noticed their color change. So McCord & Allen obtained cow brains, extracted the pineal glands and fed them to tadpoles. Within 30 to 60 minutes, depending on the concentration, the tadpoles fed with pineal extract changed color from dark to light (see picture).
Fast forward now to 1958 when an MD PhD called Aaron B. Lerner with an interest in dermatology thought that whatever was responsible for the skin color changes in the McCord & Allen (1917) paper might be useful in treating skin diseases. But first he had to extract the substance from the pineal glands and he and his colleagues had better tools for this task than the mere alcohol and acetone of his brethren of 40 years ago.
Lerner et al. (1958) made full use of the then-recently discovered paper chromatography and some standard biochemistry techniques for the time like Soxhlet extraction and fluorescence spectroscopy and discovered a substance that can lighten frog skin color and can inhibit the melanocyte stimulating hormone (MSH). “It is suggested that this substance be called melatonin” (p. 2587). Lerner and his colleagues also isolated the MSH and cryoglobulin.
Changing skin color is one of melatonin’s minor roles; its main function is to regulate circadian rhythms like sleep and awake cycles in animals (it has an oxidative stress protection in plants). Melatonin, in animals, is produced by the pineal gland only, more during the night, less during the day. Pineal gets information about the day/night cycles from the eyes. In some countries melatonin is sold as an over the counter soporific, i.e. sleeping pill.
1) McCord CP & Allen FP (Jan 1917). Evidences associating pineal gland function with alterations in pigmentation. Journal of Experimental Zoology, Part A, 23 (1): 207–224, DOI: 10.1002/jez.1400230108 ARTICLE
2) Lerner AB, Case JD, Takahashi Y, Lee TH, & Mori W (May 1958). Isolation of Melatonin, the Pineal Gland Factor that Lightens Melanocytes. Journal of the American Chemical Society, 80 (10), p. 2587–2587, DOI: 10.1021/ja01543a060 ARTICLE (although JACS gives access only to the first page of a paper, the fact that this article is only half a page makes their endeavour useless in this case)
By Neuronicus, 18 March 2017
Ultraviolet irradiation exposure from our sun accelerates the skin aging, process called photoaging. It can even cause skin cancers. There has been some considerable research on how our beloved sun does that.
For example, one way the UV radiation leads to skin damage is by promoting the production of free radicals as reactive oxygen species (ROS), which do many bad things, like direct DNA damage. Another bad thing done by ROS is the upregulation of the mitogen-activated protein kinase (MAPK) signaling pathway which activates all sorts of transcription factors which, in turn, produce proteins that lead to collagen degradation and voilà, aged skin. I know I lost some of you at the MAPK point; you can think of MAPK as a massive proteinaceous hub, a multi-button console with many inputs and outputs. A very sensitive and incredibly complex hub that controls nearly all important aspects of cell function, with many feedback loops, so if you mess with it, cell Armageddon may be happening. Or nothing at all. It’s that complex.
But I digress. What MAPK is doing is less relevant for the paper I am introducing to you today than the fact that we have physiological markers for skin aging due to UV. Bravo et al. (2017) cultured human skin cells in a Petri dish, treated them with various concentrations of an extract of passion fruit (Passiflora tarminiana) and then bombarded them with UV (the B type, 280–315 nm). The authors made the extract themselves, is not something you just buy (yet).
The UV produced the expected damage, translated as increased matrix mettoproteinase-1 (MMP-1), collagenase, and ROS production and decreased procollagen. Pretreatment with passion fruit extract significantly mitigated these UV effects in a dose-dependant manner. The concentration of their concoction that worked best was 10 μg/mL. Then the authors did some more chemistry to figure out what in their concoction is responsible, or at least probably responsible, for the observed wonderful effects. The authors believe the procyianidins and flavonoids are the culprits because 1) they have been proven to be strong antioxidants before and 2) this plant has them in very high amounts.
Good news then for the antiaging cosmetics industry. Perhaps even for dermatologists and their patients.
Reference: Bravo K, Duque L, Ferreres F, Moreno DA, & Osorio E. (EPUB ahead of print: 3 Feb 2017). Passiflora tarminiana fruits reduce UVB-induced photoaging in human skin fibroblasts. Journal of Photochemistry and Photobiology, 168: 78-88. PMID: 28189068, DOI: 10.1016/j.jphotobiol.2017.01.023. ARTICLE
By Neuronicus, 13 February 2017
Aging is being quite extensively studied these days and here is another advance in the field. Pardo et al. (2017) looked at what happens in the hippocampus of 2-months old (young) and 28-months old (old) female rats. Hippocampus is a seahorse shaped structure no more than 7 cm in length and 4 g in weight situated at the level of your temples, deep in the brain, and absolutely necessary for memory.
First the researchers tested the rats in a classical maze test (Barnes maze) designed to assess their spatial memory performance. Not surprisingly, the old performed worse than the young.
Then, they dissected the hippocampi and looked at neurogenesis and they saw that the young rats had more newborn neurons than the old. Also, the old rats had more reactive microglia, a sign of inflammation. Microglia are small cells in the brain that are not neurons but serve very important functions.
After that, the researchers looked at the hippocampal transcriptome, meaning they looked at what proteins are being expressed there (I know, transcription is not translation, but the general assumption of transcriptome studies is that the amount of protein X corresponds to the amount of the RNA X). They found 210 genes that were differentially expressed in the old, 81 were upregulated and 129 were downregulated. Most of these genes are to be found in human too, 170 to be exact.
But after looking at male versus female data, at human and mouse aging data, the authors came up with 11 genes that are de-regulated (7 up- and 4 down-) in the aging hippocampus, regardless of species or gender. These genes are involved in the immune response to inflammation. More detailed, immune system activates microglia, which stays activated and this “prolonged microglial activation leads to the release of pro-inflammatory cytokines that exacerbate neuroinflammation, contributing to neuronal loss and impairment of cognitive function” (p. 17). Moreover, these 11 genes have been associated with neurodegenerative diseases and brain cancers.
These are the 11 genes: C3 (up), Cd74 (up), Cd4 (up), Gpr183 (up), Clec7a (up), Gpr34 (down), Gapt (down), Itgam (down), Itgb2 (up), Tyrobp (up), Pld4 (down).”Up” and “down” indicate the direction of deregulation: upregulation or downregulation.
I wish the above sentence was as explicitly stated in the paper as I wrote it so I don’t have to comb through their supplemental Excel files to figure it out. Other than that, good paper, good work. Gets us closer to unraveling and maybe undoing some of the burdens of aging, because, as the actress Bette Davis said, “growing old isn’t for the sissies”.
Reference: Pardo J, Abba MC, Lacunza E, Francelle L, Morel GR, Outeiro TF, Goya RG. (13 Jan 2017, Epub ahead of print). Identification of a conserved gene signature associated with an exacerbated inflammatory environment in the hippocampus of aging rats. Hippocampus, doi: 10.1002/hipo.22703. ARTICLE
By Neuronicus, 25 January 2017
A few days ago I was reading random stuff on the internet, as is one’s procrastination proclivity, catching up after the holiday, and I exclaimed out loud: “They discovered an 100% effective Ebola Vaccine!”. I expected some ‘yeay’-s or at least some grunts along the lines of ‘that’s nice’ or ‘cool’. Naturally, I turned around from my computer to check the source of unaccustomed silence to the announcement of such good news or, at least, to make sure that everybody is still breathing and present in the room. What met my worried glare was a gloom face and a shaking head. That’s because news like that are misleading, because, duh, it finally dawned on me, there is no such thing as ‘100% effective vaccine’.
And yet…, and yet this is exactly what Henao-Restrepo et al. (2016) say they found! The study is huge, employing more that 10 000 people. Such a tremendous endeavor has been financed by WHO (World Health Organization) and various departments from several countries (UK, USA, Switzerland, South Africa, Belgium, Germany, France, Guinea, and Norway) and, I’m assuming, a lot of paid and unpaid volunteers. I cannot even imagine the amount of work and the number of people that made this happen. And the coordination required for such speedy results!
The successful vaccine in rodents and non-human primates, called the recombinant, replication-competent, vesicular stomatitis virus-based vaccine expressing the glycoprotein of a Zaire Ebolavirus (rVSV-ZEBOV) has been taken to the Republic of Guinea and rapidly administered to volunteers who were in contact with somebody that had Ebola symptoms. And their contacts. I mean the contacts and the contacts of contacts of the Ebola patient. Who were contacted by the researchers within 2 days of a new Ebola case based on the patient’s list of contacts. And of contacts of contacts. Is not that complicated, honest.
After vaccinations, the “vaccinees were observed for 30 min post-vaccination and at home visits on days 3, 14, 21, 42, 63, and 84” (p.4). Some volunteers received the vaccine immediately, others after 3 weeks. No one who received the vaccine immediately developed Ebola, which lead the researchers to claim that the vaccine is 100% effective. Only 9 from the delayed vaccination group developed Ebola within 10 days of vaccination, but the researchers figured that these people probably contacted Ebola prior to the vaccination, since the disease requires typically about 10 days to show its ugly horns.
So this is great news. Absolutely great. Even if, as always, I could nitpick thorough the paper, squabble over the “typically” 10-day incubation period, and cock an eyebrow at the new-fangled ring vaccination design as opposed to the old-fashioned placebo approach. Even after these minor criticisms this is – I repeat – GREAT NEWS!
P.S. Don’t ever say that the UN didn’t do anything for you.
Reference: Henao-Restrepo AM, Camacho A, Longini IM, Watson CH, Edmunds WJ, Egger M, Carroll MW, Dean NE, Diatta I, Doumbia M, Draguez B, Duraffour S, Enwere G, Grais R, Gunther S, Gsell PS, Hossmann S, Watle SV, Kondé MK, Kéïta S, Kone S, Kuisma E, Levine MM, Mandal S, Mauget T, Norheim G, Riveros X, Soumah A, Trelle S, Vicari AS, Røttingen JA, Kieny MP. (22 Dec 2016). Efficacy and effectiveness of an rVSV-vectored vaccine in preventing Ebola virus disease: final results from the Guinea ring vaccination, open-label, cluster-randomised trial (Ebola Ça Suffit!). Lancet. pii: S0140-6736(16)32621-6. doi: 10.1016/S0140-6736(16)32621-6. PMID: 28017403 [Epub ahead of print] ARTICLE | FREE FULLTEXT PDF | Good Nitpicking in The Conversation
By Neuronicus, 18 January 2017
Whoever didn’t roll out a tongue to catch a few snowflakes? Probably only those who never encountered snow.
The bad news is that snow, particularly urban snow is bad, really bad for you. The good news is that this was not always the case. So there is hope that in the far future it will be pristine again.
Nazarenko et al. (2016) constructed a very clever contraption that reminds me of NASA space exploration instruments. The authors refer to this by the humble name of ‘environmental chamber’, but is in fact a complex construction with different modules designed to measure out how car exhaust and snow interact (see Fig. 1).
After many experiments, researchers concluded that snow absorbs pollutants very effectively. Among the many kinds of organic compounds soaked by snow in just one hour after exposure to fume exhaust, there were the infamous BTEX (benzene, toluene, ethylbenzene, and xylenes). The amounts of these chemicals in the snow were not at all negligible; to give you an example, the BTEX concentration increased from virtually 0 to 50 and up to 380 ug kg-1. The authors provide detailed measurements for all the 40+ compounds they have identified.
Needles to say, many these compounds are known carcinogenics. Snow absorbs them, alters their size distributions, and then it melts… Some of them may be released back in the air as they are volatile, some will go in the ground and rivers as polluted water. After this gloomy reality check, I’ll leave you with the words of the researchers:
“The accumulation and transfer of pollutants from exhaust – to snow – to meltwater need to be considered by regulators and policy makers as an important area of focus for mitigation with the aim to protect public health and the environment” (p. 197).
Reference: Nazarenko Y, Kurien U, Nepotchatykh O, Rangel-Alvarado RB, & Ariya PA. (Feb 2016). Role of snow and cold environment in the fate and effects of nanoparticles and select organic pollutants from gasoline engine exhaust. Environmental Science: Processes & Impacts, 18(2):190-199. doi: 10.1039/c5em00616c. ARTICLE | FREE FULTEXT PDF
By Neuronicus, 26 December 2016
There is no news or surprise that strong hits to the head produce transient or permanent brain damage. But how about mild hits produced by light objects like, say, a volley ball or soccer ball?
During a game of soccer, a player is allowed to touch the ball with any part of his/her body minus the hands. Therefore, hitting the ball with the head, a.k.a. soccer heading, is a legal move and goals marked through such a move are thought to be most spectacular by the refined connoisseur.
A year back, in 2015, the United States Soccer Federation forbade the heading of the ball by children 10 years old and younger after a class-action lawsuit against them. There has been some data that soccer players display loss of brain matter that is associated with cognitive impairment, but such studies were correlational in nature.
Now, Di Virgilio et al. (2016) conducted a study designed to explore the consequences of soccer heading in more detail. They recruited 19 young amateur soccer players, mostly male, who were instructed to perform 20 rotational headings as if responding to corner kicks in a game. The ball was delivered by a machine at a speed of approximately 38 kph. The mean force of impact for the group was 13.1 ± 1.9 g. Immediately after the heading session and at 24 h, 48 h and 2 weeks post-heading, the authors performed a series of tests, among which are a transcranial magnetic stimulation (TMS) recording, a cognitive function assessment (by using the Cambridge Neuropsychological Test Automated Battery), and a postural control test.
Not being a TMS expert myself, I was wondering how do you record with a stimulator? TMS stimulates, it doesn’t measure anything. Or so I thought. The authors delivered brief (1 ms) stimulating impulses to the brain area that controls the leg (primary motor cortex). Then they placed an electrode over the said muscle (rectus femoris or quadriceps femoris) and recorded how the muscle responded. Pretty neat. Moreover, the authors believe that they can make inferences about levels of inhibitory chemicals in the brain from the way the muscle responds. Namely, if the muscle is sluggish in responding to stimulation, then the brain released an inhibitory chemical, like GABA (gamma-amino butyric acid), hence calling this process corticomotor inhibition. Personally, I find this GABA inference a bit of a leap of faith, but, like I said, I am not fully versed in TMS studies so it may be well documented. Whether or not GABA is responsible for the muscle sluggishness, one thing is well documented though: this sluggishness is the most consistent finding in concussions.
The subjects had impaired short term and long term memory functions immediately after the ball heading, but not 24 h or more later. Also transient was the corticomotor inhibition. In other words, soccer ball heading results in measurable changes in brain function. Changes for the worst.
Even if these changes are transient, there is no knowing (as of yet) what prolonged ball heading might do. There is ample evidence that successive concussions have devastating effects on the brain. Granted, soccer heading does not produce concussions, at least in this paper’s setting, but I cannot think that even sub-concussion intensity brain disruption can be good for you.
On a lighter note, although the title of the paper features the word “soccer”, the rest o the paper refers to the game as “football”. I’ll let you guess the authors’ nationality or at least the continent of provenance ;).
Reference: Di Virgilio TG, Hunter A, Wilson L, Stewart W, Goodall S, Howatson G, Donaldson DI, & Ietswaart M. (Nov 2016, Epub 23 Oct 2016). Evidence for Acute Electrophysiological and Cognitive Changes Following Routine Soccer Heading. EBioMedicine, 13:66-71. PMID: 27789273, DOI: 10.1016/j.ebiom.2016.10.029. ARTICLE | FREE FULLTEXT PDF
By Neuronicus, 20 December 2016