By Neuronicus, 10 September 2017
By Neuronicus, 10 September 2017
Alzheimer’s Disease (AD) is the most common type of dementia with a progression that can span decades. Its prevalence is increasing steadily, particularly in the western countries and Australia. So some researchers speculated that this particular disease might be specific to humans. For various reasons, either genetic, social, or environmental.
A fresh e-pub brings new evidence that Alzheimer’s might plague other primates as well. Edler et al. (2017) studied the brains of 20 old chimpanzees (Pan troglodytes) for a whole slue of Alzheimer’s pathology markers. More specifically, they looked for these markers in brain regions commonly affected by AD, like the prefrontal cortex, the midtemporal gyrus, and the hippocampus.
Alzheimer’s markers, like Tau and Aβ lesions, were present in the chimpanzees in an age-dependent manner. In other words, the older the chimp, the more severe the pathology.
Interestingly, all 20 animals displayed some form of Alzheimer’s pathology. This finding points to another speculation in the field which is: dementia is just part of normal aging. Meaning we would all get it, eventually, if we would live long enough; some people age younger and some age older, as it were. This hypothesis, however, is not favored by most researchers not the least because is currently unfalsifiable. The longest living humans do not show signs of dementia so how long is long enough, exactly? But, as the authors suggest, “Aβ deposition may be part of the normal aging process in chimpanzees” (p. 24).
Unfortunately, “the chimpanzees in this study did not participate in formal behavioral or cognitive testing” (p. 6). So we cannot say if the animals had AD. They had the pathological markers, yes, but we don’t know if they exhibited the disease as is not uncommon to find these markers in humans who did not display any behavioral or cognitive symptoms (Driscoll et al., 2006). In other words, one might have tau deposits but no dementia symptoms. Hence the title of my post: “Old chimpanzees get Alzheimer’s pathology” and not “Old chimpanzees get Alzheimer’s Disease”
Good paper, good methods and stats. And very useful because “chimpanzees share 100% sequence homology and all six tau isoforms with humans” (p. 4), meaning we have now a closer to us model of the disease so we can study it more, even if primate research has taken significant blows these days due to some highly vocal but thoroughly misguided groups. Anyway, the more we know about AD the closer we are of getting rid of it, hopefully. And, soon enough, the aforementioned misguided groups shall have to face old age too with all its indignities and my guess is that in a couple of decades or so there will be fresh money poured into aging diseases research, primates be damned.
REFERENCE: Edler MK, Sherwood CC, Meindl RS, Hopkins WD, Ely JJ, Erwin JM, Mufson EJ, Hof PR, & Raghanti MA. (EPUB July 31, 2017). Aged chimpanzees exhibit pathologic hallmarks of Alzheimer’s disease. Neurobiology of Aging, PII: S0197-4580(17)30239-7, DOI: http://dx.doi.org/10.1016/j.neurobiolaging.2017.07.006. ABSTRACT | Kent State University press release
By Neuronicus, 23 August 2017
Nathan Lo is an evolutionary biologist interested in creepy crawlies, i.e. arthropods. Well, he’s Australian, so I guess that comes with the territory (see what I did there?). While postdoc’ing, he and his colleagues published a paper (Sassera et al., 2006) that would seem boring for anybody without an interest in taxonomy, a truly under-appreciated field.
The paper describes a bacterium that is a parasite for the mitochondria of a tick species called Ixodes ricinus, the nasty bugger responsible for Lyme disease. The authors obtained a female tick from Berlin, Germany and let it feed on a hamster until it laid eggs. By using genetic sequencing (you can use kits these days to extract the DNA, do PCR, gels and cloning, pretty much everything), electron microscopy (real powerful microscopes) and phylogenetic analysis (using computer softwares to see how closely related some species are) the authors came to the conclusion that this parasite they were working on is a new species. So they named it. And below is the full account of the naming, from the horse’s mouth, as it were:
“In accordance with the guidelines of the International Committee of Systematic Bacteriology, unculturable bacteria should be classified as Candidatus (Murray & Stackebrandt, 1995). Thus we propose the name ‘Candidatus Midichloria mitochondrii’ for the novel bacterium. The genus name Midichloria (mi.di.chlo′ria. N.L. fem. n.) is derived from the midichlorians, organisms within the fictional Star Wars universe. Midichlorians are microscopic symbionts that reside within the cells of living things and ‘‘communicate with the Force’’. Star Wars creator George Lucas stated that the idea of the midichlorians is based on endosymbiotic theory. The word ‘midichlorian’ appears to be a blend of the words mitochondrion and chloroplast. The specific epithet, mitochondrii (mi.to′chon.drii. N.L. n. mitochondrium -i a mitochondrion; N.L. gen. n. mitochondrii of a mitochondrion), refers to the unique intramitochondrial lifestyle of this bacterium. ‘Candidatus M. mitochondrii’ belongs to the phylum Proteobacteria, to the class Alphaproteobacteria and to the order Rickettsiales. ‘Candidatus M. mitochondrii’ is assigned on the basis of the 16S rRNA (AJ566640) and gyrB gene sequences (AM159536)” (p. 2539).
George Lucas gave his blessing to the Christening (of course he did).
Acknowledgements: Thanks go to Ms. BBD who prevented me from making a fool of myself – this time – on the social media by pointing out to me that midichloria are real and that they are a mitochondrial parasite.
REFERENCE: Sassera D, Beninati T, Bandi C, Bouman EA, Sacchi L, Fabbi M, Lo N. (Nov. 2006). ‘Candidatus Midichloria mitochondrii’, an endosymbiont of the tick Ixodes ricinus with a unique intramitochondrial lifestyle. International Journal of Systematic and Evolutionary Microbiology, 56(Pt 11): 2535-2540. PMID: 17082386, DOI: 10.1099/ijs.0.64386-0. ABSTRACT | FREE FULLTEXT PDF
By Neuronicus, 29 July 2017
REFERENCE: Burns CS, Heyerick A, De Keukeleire D, Forbes MD. (5 Nov 2001). Mechanism for formation of the lightstruck flavor in beer revealed by time-resolved electron paramagnetic resonance. Chemistry – The European Journal, 7(21): 4553-4561. PMID: 11757646, DOI: 10.1002/1521-3765(20011105)7:21<4553::AID-CHEM4553>3.0.CO;2-0. ABSTRACT
By Neuronicus, 12 July 2017
Few people seem to know that although global warming and climate change are hotly debated topics right now (at least on the left side of the Atlantic) the effect of CO2 levels on the planet’s surface temperature was investigated and calculated more than a century ago. CO2 is one of the greenhouse gases responsible for the greenhouse effect, which was discovered by Joseph Fourier in 1824 (the effect, that is).
Let’s start with a terminology clarification. Whereas the term ‘global warming’ was coined by Wallace S. Broecker in 1975, the term ‘climate change’ underwent a more fluidic transformation in the ’70s from ‘inadvertent climate modification’ to ‘climatic change’ to a more consistent use of ‘climate change’ by Jule Charney in 1979, according to NASA. The same source tells us:
“Global warming refers to surface temperature increases, while climate change includes global warming and everything else that increasing greenhouse gas amounts will affect”.
But before NASA there was one Svante August Arrhenius (1859–1927). Dr. Arrhenius was a Swedish physical chemist who received the Nobel Prize in 1903 for uncovering the role of ions in how electrical current is conducted in chemical solutions.
S.A. Arrhenius was the first to quantify the variations of our planet’s surface temperature as a direct result of the amount of CO2 (which he calls carbonic acid, long story) present in the atmosphere. For those – admittedly few – nitpickers that say his views on the greenhouse effect were somewhat simplistic and his calculations were incorrect I’d say cut him a break: he didn’t have the incredible amount of data provided by the satellites or computers, nor the work of thousands of scientists over a century to back him up. Which they do. Kind of. Well, the idea, anyway, not the math. Well, some of the math. Let me explain.
First, let me tell you that I haven’t managed to pass past page 3 of the 39 pages of creative mathematics, densely packed tables, parameter assignments, and convoluted assumptions of Arrhenius (1896). Luckily, I convinced a spectroscopist to take a crack at the original paper since there is a lot of spectroscopy in it and then enlighten me.
Second, despite his many accomplishments, including being credited with laying the foundations of a new field (physical chemistry), Arrhenius was first and foremost a mathematician. So he employed a lot of tedious mathematics (by hand!) together with some hefty guessing along with what was known at the time about Earth’s infrared radiation, solar radiation, water vapor and CO2 absorption, temperature of the Moon, greenhouse effect, and some uncalibrated spectra taken by his predecessors to figure out if “the mean temperature of the ground [was] in any way influenced by the presence of the heat-absorbing gases in the atmosphere” (p. 237). Why was he interested in this? We find out only at page 267 after a lot of aforesaid dreary mathematics where he finally shares this with us:
“I certainly not have undertaken these tedious calculations if an extraordinary interest had not been connected with them. In the Physical Society of Stockholm there have been occasionally very lively discussions on the probable causes of the Ice Age”.
So Arrhenius was interested to find out if the fluctuations of CO2 levels could have caused the Ice Ages. And yes, he thinks that could have happened. I don’t know enough about climate science to tell you if this particular conclusion of his is correct today. But what he managed to accomplish though was to provide for the first time a way to mathematically calculate the amount of rise in temperature due the rise of CO2 levels. In other words, he found a direct relationship between the variations of CO2 and temperature. Today, it turns out that his math was incorrect because he left out some other variables that influence the global temperature that were discovered and/or understood later (like the thickness of the atmosphere, the rate of ocean absorption of CO2 and others which I won’t pretend I understand). Nevertheless, Arrhenius was the first to point out to the following relationship, which, by and large, is still relevant today:
“Thus if the quantity of carbonic acid increased in geometric progression, the augmentation of the temperature will increase nearly in arithmetic progression” (p. 267).
P.S. Technically, Joseph Fourier should be credited with the discovery of global warming by increasing the levels of greenhouse gases in the atmosphere in 1824, but Arrhenius quantified it so I credited him. Feel fee to debate :).
REFERENCE: Arrhenius, S. (April 1896). XXXI. On the Influence of Carbonic Acid in the Air upon the Temperature of the Ground, The London, Edinburgh, and Dublin Philosophical Magazine and Journal of Science (Fifth Series), 49 (251): 237-276. General Reference P.P.1433. doi: http://dx.doi.org/10.1080/14786449608620846. FREE FULLTEXT PDF
By Neuronicus, 24 June 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 on 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 (Michel 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 commissure, 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 from 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 recently 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 the day and more during the 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 adaptation 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
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