Showing posts with label brain. Show all posts
Showing posts with label brain. Show all posts

The Resin For The Season

Biology concepts – sap, resin, latex, mucilage

Frankincense is a solid material than starts out as a 
liquid that oozes from a tree. In the presence of air, 
the resin turns hard. When burned, many 
fragrant and brain altering compounds are released.
We saw last week that gold doesn't just look good, it has a significant place in biology. This week we take a look at frankincense, a natural tree product prized for its use in sacred rituals. The Catholic Church is the number one purchaser of frankincense, but that may be about to change, especially for medicine. The wise men must have done some heavy thinking before they made their gift choices for Jesus – gift cards are so impersonal.

A 2008 study may have defined just why frankincense is used in religious rituals. Burning the resin releases incensole acetate (IA), one of the resin’s key components, which activates transient receptor potential vanilloid (TRPV3) ion channels in the skin and brain. This ion channel is responsible for mediating a warm feeling in the skin, but TRPV3 channels also mediate brain activity.

The researchers in Israel found that IA activates the cFos transcription factor in the brain, leading to anxiolytic (anxio = anxiety, and lytic = destroying) and anti-depressive feelings. Mice without TRPV3 channels did not show cFos activation or behavior changes when exposed to IA. It appears that burning frankincense makes one feel happier and more in tune with whatever activity is going on at the time, including religious rituals.

The fact that there is a psychoactive agent in frankincense is amazing enough, but there’s more biology to this second gift. Recent evidence indicates that the oils and other compounds in frankincense may save lives– if the trees that produce frankincense don’t disappear in the next 50 years. Unfortunately, their extinction is a distinct possibility – we must save this precious sap, or resin, or whatever it is.

Trees can produce various oozings and liquids. Pancake syrup most often comes from the sap of a maple tree, while your stick of Wrigley’s spearmint uses the latex that exude from many different kinds of plants. Gum drippings may also be used in chewing gum (Chiclets used chicle gum), but gums are now more commonly found in paints and erasers. The aloe vera you use on burns is a type of mucilage, rich in glycoproteins. But many plants, especially coniferous trees, exude resins when they are under attack or are damaged.

Amber is fossilized resin. Scientists learn much from organisms caught 
in it and thus preserved. Recent evidence also shows that amber can 
help us track bug attacks on plants from the days of dinosaurs. 
Gum is semi-solid, and rubbery. The gum shown is chicle, used 
for many years in Chiclets gum. Mucilage is produced by 
many pants, including as a treat and trap for insects in carnivorous
plants like this sundew. Maple sap is clear and dilute when tapped from
a tree. It must be boiled for hours to reduce it to syrup. Latex rubber is 
naturally white. The first car and bicycle tires were all white, not
just white-walled.
Gums can also be used for defense, but are made directly from disintegrating internal plant material. They harden to a certain degree after being exuded from the plant tissue, but are more known for their ability to increase the viscosity of a liquid, due to their long polysaccharide molecules. Bacterial agar plates use a gum from seaweed to grow microorganisms.

Sap is the sugary fluid that travels up and down in the xylem of vascular plants, providing the different structures with carbohydrate to produce ATP at the cellular level. Therefore, sap is a nutritive liquid and all trees produce it – but not all taste good.

Mucilage is similar to sap. It also contains glycoproteins and other carbohydrate-containing molecules, and is important for food and water storage in almost all plants, especially cacti. However, mucilage can be used for other purposes, like luring insects into carnivorous plant traps, such as the flypaper plant.

People used to lick mucilage everyday, but technology has reduced its role in our lives. When mixed with water, mucilage is an adhesive, like on the backs of stamps. You don’t have to lick your computer screen to send an e-mail, so mucilage is less important to us in these modern times.

Resins become definite solids when exposed to air. They are not nutritive, and contain primarily the byproducts and secondary metabolites of other cellular processes. While gums and saps are soluble (will dissolve) in water or fat, resins are stable in water but will dissolve in alcohol.

The reason for resin production is not fully understood. They may play a role in defense or tissue injury, but may instead serve to rid the plant of unneeded or unwanted waste products. Indeed, when trees are cut to harvest frankincense, the first resin produced is discarded, because it contains many toxins and foul smelling chemicals.

The Boswellia sacra tree grows in a harsh
environment. The roots can grip onto stones and
they grow out of the ground as buttresses to keep
the tree stable on the cliff sides.
Resinsare produced mostly by coniferous trees (like pine trees). This makes frankincense an exception, since it comes from the Boswellia sacratree, a deciduous tree (trees that lose their leaves in the winter). Frankincense is different from other resins in another aspect as well, it is technically a gum resin, since it has many compounds that are of the gum variety within its resin. The gum-like essential oils in frankincense are one of the reasons it is sought after as an incense.

B. sacra grows only in the middle eastern countries of Yemen and Oman, and possibly in Somalia. The tree is only 2-7 meters (6-23 ft.) when fully grown, and starts producing resin at a fairly young age of 8-10 years. Its small stature may be due in part to the arid climate that it lives in; there is so little water to be had that B. sacra survives only on the moisture it absorbs from fog.

However uninviting its environment might seem, B. sacra is well adapted to this area and is very finicky in growing anywhere else. In fact, a recent study indicates that they are more finicky than even previously believed. Though living in two different areas (Oman/Yemen vs. Somalia), it had been accepted that these plants were the same species. But based on chemical evaluation of the essential oils of the resins from trees in these two regions, the Oman/Yemen trees of B. sacra are truly different than the B. carterii trees of Somalia.

Initial gas chromatography-mass spectrum analysis did not show significant differences in the kinds of volatile molecules present, but there were large differences in the amounts of the individual compounds in the resin from each species of tree. Later experiments also showed chemical differences in the same compounds from each species.

Yemen and Oman are side by side and Somalia is
just across the Gulf of Aden. But recent studies show
that the frankincense trees that grow in Yemen and
Oman are distinctly different from those in Somalia.
This speciation difference shows that B. sacra REALLY likes to stay close to home. There’s nothing wrong with that, except that the small area that it grows in happens to be one of the most unstable parts of the world. The trees have been over harvested for resin, and this affects the rate at which the trees reproduce. Heavily tapped trees have seeds that germinate only 8-16% of the time, while trees that have not been tapped for resin germinate seeds at a rate of over 80%.

Add goats grazing on the existing trees, global warming, fires, and low genetic diversity in individual stands of trees to the low rate of propagation and this spells trouble for the B. sacra species. Estimates are as dire as a 50% decrease in frankincense production in the next 15 years, to a 90% loss of trees in the next 50 years – but there is hope.

A recent DNA study shows that trees from different parts of the Dhofar region are genetically distinct, and that there is a low level of heterozygosity in the trees of a single area. This low level of genetic diversity results in trees less able to survive changes in environment or biology (genetic diversity is key to natural selection). But some stands show more genetic diversity and arguments are now being made to initiate conservation efforts for the diverse stands, while increasing cross-pollination of the least genetically diverse trees. It is hoped that these efforts, as well as attempts to grow B. sacra in the Sonora Desert of North America, could stave off extinction of B. sacra.
 
The hippocampus is important in your sense of well-
being. Studies have shown that in people with
depression, the hippocampus is smaller, perhaps from
poor neurogenesis or from increased cell death. Why
the seahorse? In Greek, hippocampus means, “horse sea
monster.” I can see the resemblance.
Whyis it important that we save the frankincense trees? Because it is becoming evident that the resinous compounds in frankincense could have great medical benefits to humans – and unhappy mice.

We mentioned above that IA (incensole acetate) of frankincense acts on the brain to increase feelings of well-being. Mice bred to be submissive and to give up (quit) earlier in a test of depressive activity show a much stronger will to live and more positive behaviors when given IA. Recent research in Israel shows that IA influences brain molecular biology, especially in the hippocampus, altering depressive behaviors as much as other chemical interventions. It is hoped that IA may be a viable anti-depressant drug in the future.

This same group showed in 2008 that IA was a significant anti-inflammatory agent, through its inhibitor action on an important transcription factor (called NF-kB) that stimulates expression of inflammatory proteins. In mice with traumatic brain injuries, IA administration resulted in reduced inflammation and pressure on the brain, reduced neuron degeneration, and prevented loss of cognitive function. Their more recent study also indicates that IA is protective in stroke and in the damage that can come after strokes by reintroducing oxygen into the damage part of the brain (when blood flow resumes).

Boswellic acid is also of use in myeloid leukemia, a type
of cancer of the white blood cells. It seems that BA can
induce the cancer cells to commit suicide, and die after a
period of time like most cells do. BA trigger apoptosis by
stimulating the release of important compounds from the
mitochondria, suggesting to the cell that its energy making
organelles are irreparably damaged.
Anothercompound in frankincense is showing promise as an anti-cancer drug. An essential oil molecule called Boswellic Acid (BA) has been shown to slow the rate of cancer cell growth. A recent study has delineated at least part of the mechanism of BA-mediated inhibition of colorectal tumor growth.

Cancer is the result of mutations in genes that code for the production of proteins that keep cells living, growing, and dividing forever. BA stops the synthesis of some of these proteins. It turns out that BA stimulates production of a micro RNA (miRNA, a short RNA molecule of about 22 nucleotides) that can bind to the messages transcribed from DNA that would be translated into pro-cancer proteins and stop the proteins from being made. Do you think the three kings had any idea that they were giving a gift that can stop inflammation, depression, and cancer – or they did they just think it smelled nice?

Next week – the third Christmas gift, myrrh.

Takahashi, M., Sung, B., Shen, Y., Hur, K., Link, A., Boland, C., Aggarwal, B., & Goel, A. (2012). Boswellic acid exerts antitumor effects in colorectal cancer cells by modulating expression of the let-7 and miR-200 microRNA family Carcinogenesis, 33 (12), 2441-2449 DOI: 10.1093/carcin/bgs286

Moussaieff, A., Gross, M., Nesher, E., Tikhonov, T., Yadid, G., & Pinhasov, A. (2012). Incensole acetate reduces depressive-like behavior and modulates hippocampal BDNF and CRF expression of submissive animals Journal of Psychopharmacology, 26 (12), 1584-1593 DOI: 10.1177/0269881112458729

Coppi, A., Cecchi, L., Selvi, F., & Raffaelli, M. (2010). The Frankincense tree (Boswellia sacra, Burseraceae) from Oman: ITS and ISSR analyses of genetic diversity and implications for conservation Genetic Resources and Crop Evolution, 57 (7), 1041-1052 DOI: 10.1007/s10722-010-9546-8
 
For more information, see:

Resin –

Sap –

Gum –

Latex –

Mucilage –

Boswellia sacra –
http://www.iucnredlist.org/details/34533/0
 

The Best Cure for Insomnia Is To Get A Lot Of Sleep

Biology concepts – theories of sleep, REM sleep, circadian rhythms, neural plasticity

You open the door to your house and find your roommate sprawled out on the couch. Is he sleeping, unconscious, or dead? Knowing your roommate, you figure it could be any of them – you stop yourself short of naming a preference.


You find your roommate passed out in his underwear,
and can’t decide if he is sleeping, unconscious or dead.
If you have chosen Homer as a roommate, you have
already clued us in to your decision-making abilities.
The live/dead question is easy; hold a mirror under his nose and see if it fogs up. If he’s not breathing, there’s only one thing to do – go through his pockets and look for loose change (with a nod to “The Princess Bride”). But if you do see condensation, how do you decide if he is passed out or just sleeping - or are you considered unconscious when sleeping?

Sleep is voluntary, at least most of the time. I try to stay awake at the ballet, but I don’t always succeed. But besides drinking yourself into a stupor, going unconscious is usually not voluntary. Unfortunately (or fortunately), you weren’t there to see what preceded the crease marks on your roommate’s face or his drooling on the couch pillow, so how can you identify his state?

Sleeping implies that one has a diminished ability to respond to external stimuli with reduced sensory perception. However, unconsciousness appears much the same. The difference lies in the degree of diminished capacity; you can be roused more easily from sleep and perhaps not at all from deeper unconsciousness. Some people I know must pass out every night, because they are tough to wake up. You might parse the difference and just say that sleep is more easily rousable unconsciousness.

Sleep has stages and these stages have cycles. If deprived
of a particular stage the night before, your body will
change your cycles so that you make up the lost time in
that stage on the next night. Source for image: http://xavier 
appsychology.wikispaces.com/Chapter+5,+ Period+6
A more profound difference between the two exists, but you won’t be able to detect it in your roommate without monitoring his brain waves. In sleep, you go through different phases, each with characteristic brain wave patterns. In 2007, a revised set of sleep stages was published, identifying 4 distinct phases, although stages 2 and 4 are repeated more than twice. Stage 4 is REM sleep, in which many many animals dream.

In general, the safer an animal is, the more it dreams. Predators dream more than prey and big species dream more than small species, though there are several exceptions to this rule. For example, ruminants (cows, deer, goats, and buffalo) dream very little (about 5 minutes/night), and cetaceans (whales, dolphins, porpoises) may not dream at all.

In contrast, animals that are born immature (not able to live on their own) tend to experience lots of REM sleep. These altricial (meaning “requiring nourishment") animals, including marsupials, cats, dogs, and most rodents, may have 6-8 hours of REM sleep a night. What is more, as adults they continue to dream heavily – about what, I have no idea.


Do you know the differences between dolphins and porpoises? Dolphins have longer bodies and snouts, and porpoises have a straight front edge on their dorsal fin. But, they are both cetaceans and have the same sleep patterns. Opposums, the only marsupials in North America, have immature young, and for some reason they dream much more. They are probably dreaming about the day their kids will get off their back.
 But even this exception has an exception. Many birds are born very immature. They have no feathers, they can’t fly, they usually have their huge eyes closed, so they are definitely altricial species. But, birds have extremely short cycles of non-REM and REM sleep. Avian REM cycles might total only 5 minutes in a night, and each episode might be only 9 seconds long. What can you get done in a 9 second dream?


Brain waves recorded on an electroencephalogram
(EEG) show that dolphins and birds have normal
activity in one hemisphere while the other is at rest.
The heartbeat is constant showing that there is
normal body rhythm. This is unihemispheric sleep.
Image is taken from: Ridgeway, S. et. al. J. Exp. Med.
209:2902-2910, 2006.
REM sleep is deeper and harder to be roused from compared to non-REM sleep, the short cycles might be related to birds’ sleep pattern, which is unihemispheric (one half of the brain) in non-REM sleep, and is probably related to their need to keep watch for predators. Birds don’t lose muscle tone when they sleep; often they have to remain on a perch while they sleep. How embarrassing it would be for a bird to fall asleep and then fall off their branch- they would deserve to be eaten.

Other species of bird can sleep while flying, the arctic tern for example, whose migration can be as long as 22,000 miles one way. During flight, the eye connected the active half of the brain will remain open to navigate, but the bird will not dream, since both hemispheres are required in all animals for REM sleep.

Dreaming less doesn’t necessarily correlate with sleeping less. Animals that dream little may still sleep a considerable amount. For prey animals, sleep may represent a dicey time when they must be on the lookout. But it might also represent a way to stay motionless, blend in, and avoid predators. Either theory is practical, since predators seem to take the old, young, and diseased, whether sleeping or not.

Indisputably, every animal needs to sleep to survive, but why? It is interesting that science hasn’t quite figured this out yet. It is known that many beneficial events occur during sleep, but just being good for you doesn’t make them vital. But it must be vital, since even hibernating animals will cycle from hibernation to sleep in order to reap the benefits. Several theories exist for the necessity of sleep:

Energy conservation theory of sleep. Smaller animals carry less fat than large animals, which means they have a smaller margin of error in energy usage – they must conserve energy or feed more often. By sleeping longer, smaller animals keep their metabolic rate low and conserve more energy for when they need it, like for finding more food.

Related to this, animals with fewer predators seem to sleep longer than animals who may be hunted by many other species (as discussed above). However, since resting saves 90% as much energy as sleeping and that animals could watch for predators while resting, there clearly must be additional reasons to sleep instead of just rest.

Repair theory of sleep. This theory contends that non-REM sleep is important for repairing the physical body. Indeed, cell division and protein synthesis increase during non-REM sleep. On the other hand, REM sleep is necessary for restoring mental function, but we will leave the reasons for why we dream for another discussion.

Information packaging theory of sleep. You may sleep in order to provide the brain with time to process all that occurred the previous day, and be ready to take in more the next day. This relates to something called neural plasticity (new connections, ie. learning) and memory consolidation. Recent evidence shows that sleep deprivation harms recall, so sleep may help move information from short-term to long-term memory.


One theory of sleep is that your brain returns to a set
point so you can learn things the next day. Learning
means making new connections between neurons;
these connections are reinforced by neurotransmitters
being released to stimulate the next neuron in series. If
the neuron isn’t fired, it will not release neurotransmitters
to stimulate the next neuron in the path. If they are not
repeatedly fired, the pathway will no longer exist, and
new connections can be made.
In terms of plasticity, a 2007 study indicated that the slow brain waves in non-REM sleep are linked to our ability to learn new information. Dr. Guioli Tononi stated that neural connections become progressively weaker during slow wave sleep, so that by morning, the connections are ready to record new information, but still strong enough to hold the old memories. 


An extension of this study, published in 2011 by the same group showed that in some groups of neurons, synapse size and number was affected by the amount of sleep that fly and the amount of experience that the fly had. More experience required more sleep in order to prune the connections and strengthen those that were used repeatedly. After a few hours of wake, synapse size and number increased, and sleep was required to reduce those that are weak and strengthen the remaining circuits.

If sleep provides all these benefits, and higher animals can’t survive without it (even insects and worms have periods of inactivity that look a lot like sleep), then how is it that the giraffe sleeps only 2-4 hours per day? As prey, nature may have deemed it more important to stay alert; or maybe they just can’t find a long enough blanket.

Cetaceans, like birds, only let half their brain sleep at a time, so they probably don’t dream either. Being mammals, they still have to be able to surface to inhale and exhale while sleeping, called conscious breathing. This might require that some part of their brain be active at all times.

I say might because most cetacean sleep studies have been done in captive animals (the smaller species). But in 2008, the boat of a cetacean research team accidentally floated into the middle of a pod of inactive sperm whales. The whales were unresponsive to the researchers and had both eyes closed. This agreed with another observation that electronically tagged sperm whales spent about 7% (1.68 hr/day) of their drifting with the tide. If this is true sleep (not unihemispheric), it would be a new finding in cetaceans and would indicate that that sperm whales sleep less than any other mammal.


The American bullfrog is fully alert when inactive, so is it
asleep? Scientists think that the bullfrog is so territorial and
is such a good parent that it will not let its guard down until
it dies.
An even more amazing exception to the sleep rule is the American bullfrog (Rana catesbeiana). Brain wave studies (electroencephalography) of the nocturnally active bullfrog did show signs of rest during the day, but bullfrogs had no loss of sensory perception. They could react to stimuli just as if awake. Other frogs show similar brain waves, but are much harder to arouse. The bullfrog might be the only animal to pull a lifetime all-nighter. He should really be ready for that math test.

Nobody yet knows exactly how sleep restores the brain or why bullfrogs and giraffes need so little, but we do know that people who are deprived of sleep suffer physically, emotionally, and intellectually – or worse. How would you like to be condemned to death for not taking a nap? We’ll talk about this next time.

Daniel Bushey, Giulio Tononi, Chiara Cirelli (2011). Sleep and Synaptic Homeostasis: Structural Evidence in Drosophila Science DOI: 10.1126/science.1202839

For more information, classroom activities, and laboratories on theories of sleep, and sleep in animals, see:
sleep –


stages of sleep and REM sleep –

sleep in animals –
http://thebrain.mcgill.ca/flash/capsules/outil_jaune07.html
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