You are your brain

Sunday, September 29, 2013

Organization of Central Nervous System

Central nervous system is made up from different structures: a structure called encephalon, which is located inside the cranium and another structure called spinal cord, placed inside the spinal canal. In the base of the CNS, the spinal cord is joined to the diencephalon through the brainstem, whose components are: the medulla oblongata, the pons and the midbrain. The telencephalon lies above the diencephalon, while the cerebellum is located behind the medulla oblongata.

The spinal cord is located inside the spinal canal and, besides keeping communicated the brain with the rest of the body, it is made up from some spinal reflex circuits that take precedence over voluntary movement to those stimuli that could damage our body. There are two substances inside the spinal cord: the gray matter, which can be found in the center, and the white matter in the periphery. The gray matter contains the cell bodies of neurons, while the white matter is composed of myelinated axons. The neurons are cells composed by a body which is made up by a nucleus; also the dendrites, that are branched projections which conducts the information received from other neurons, and finally an axon terminal recovered of myelin which sends and receives electrical impulses.
The encephalon is composed of all the structures inside the cranium. In the base of the encephalon, it is found the brainstem whose components are: the medulla oblongata that continues the spinal cord structure, the pons that is made up of transverse fibers; and the mesencephalon located in the middle of the encephalon. Dislike the spinal cord, the subdivision of gray matter and white matter is not that clear since there are different gray matter nucleus which carry on both integrative and communicative functions. The brainstem is responsible of important organic functions such as cardiovascular system control, respiratory control and sleep cycle.
At the rear of brainstem, there are three peduncles connecting to the cerebellum, which is made up from the vermis and two hemispheres that are similar to those of the brain. Moreover, it could be said the cerebellum carries on all the functions of central nervous system, although it also plays an important role in language and motor learning control.

In contrast, the brain is composed of a structure made up from the diencephalon and the telencephalon. The diencephalon is located on the brainstem and is made up from the thalamus and another four components: the hypothalamus, the subthalamus, the metathalamus and the epithalamus. Each one of this structures has a specific function, the thalamus receives the sensitive information from the spinal cord and the brainstem and it is transmitted to the telencephalon. The main function of the metathalamus is the transmission of auditory and visual information to the telencephalon. The hypothalamus regulates the important functions of vegetative nervous system such as hunger, thirst and body temperature. The subthalamus is located between the fibers of a motor function associated system. Finally, the epithalamus can be identified by the pineal gland which produces melatonin that affects the modulation of wake/sleep patterns and our mood.

The telencephalon is the best-developed structure of our central nervous system, it is divided into two hemispheres: left and right, both separated by the interhemispheric fissure and connected by the corpus callosum that is an organ made up of myelinic associative fibers. The cerebral cortex is the outermost layered structure of the brain and it is characterized by its sulcus and gyrus which are necessary to increase its own area since it is limited by the cranium. The cerebral cortex is composed of five lobes: frontal, parietal, temporal, occipital and insular, which is located in the deepest part. Moreover, it can be found the limbic system which is made up from several structures with similar functions but different anatomy. The cerebral cortex is made up of the gray matter that contains the cell bodies of neurons whose axons are found in the white matter. This white matter is placed inside the telencephalon and it is known as semioval center (there is one in each hemisphere). There are large amounts of gray matter inside the white matter that are know as basal ganglia and have an important role in the motor activity. Korbinian Brodmann defined 52 distinct regions inside the cerebral cortex, each one of those divisions have a specific function. Overall, the cerebral cortex could be divided into three areas: sensory areas receive and process information from the senses., motor areas produce the different types of movements and association areas integrate information from receptors in order to produce a meaningful perception of the world.

Thursday, September 12, 2013

How do we control pain?

Nowadays it is not known so much about it, but enough to know that we are able to control the pain. For example, we know that placebo effect can make us feel better by thinking we are given a drug, or when we get hurt but we don't feel the pain within the next hours, and we have also noticed that not everybody faces the pain in the same way. The main reason is that the perception of pain depends on the circumstances and emotions involved in this situation. In terms of evolution, feeling pain could be disadvantageous in stress or emergency situations since our body must care about surviving. However, pain is something essential in the opposite situations in order to prevent further damages.

This is due to the descending control of pain which goes from the brain to the spinal cord and let our brain select those pain stimuli we want to feel. A lot of different areas in our brain has been identified to inhibit the transmission of pain sensation at the level of the spinal cord.

One of these areas is the rostral ventrolateral medula, which is located in the nucleus raphe magnus where a serotonergic pathway (release serotonin) is derived and projected to the spinal cord, thus inhibiting pain transmission. This pathway is the final part of a system that begins in another levels, in fact, the nucleus raphe magnus receives information from periaqueductal gray matter, which receives information from the cortex and the limbic system. The cortex has an important role in the thinking process, while the limbic system is responsible of the emotions and our behavior, as well as of the sense of smell and other functions. Therefore, it could be thought we can control these structures in order to elaborate the necessary information to restrict the pain sensation.

Describing in detail, rostral ventrolateral medula is made up from neurons, including on-cells and off-cells. On-cells act by activating the transmission of pain impulses, while off-cells act by inhibiting that trasmission when they are activated. These cells are the target of opioids such as morphine, which inhibits the action of on-cells and activates off-cells which produces an interruption of pain, thus causing an analgesia.

It is quite similar in a stress situation or the effects of placebo in our body, which are capable of activating endogenous opioid system by producing substances that are similar to morphine which binds to the same receptors and activate the descending pain control system. As a result, a strong analgesia will be caused by the stress or the supply of that drug.

There are some evidences to show the endogenous opioid substances our brain produces are essential for analgesia. For example, naloxone, an opioid antagonist, blocks the analgesic placebo effect, while other drugs antagonize cholecystokinin (an anti-opioid) and increase analgesic placebo effects.

Thursday, September 5, 2013

The mystery of sleep

Have you ever found yourself wondering why we sleep? Which hidden mechanism is the responsible of that apparently easy but indispensable function in our brain? Let us take a closer look of what happen while we are sleeping.

There is a transition between the wakefulness state and sleep state where the subject experiences a feeling of sleepiness and it exists a gradual disconnection from the environment around us. It is quite important the role of thalamus in this process since it acts like a "door" that blocks the stimuli coming from the outside. There are three main factors that lead us to lay in a comfortable place, close our eyes and take a little nap: vigilance factor, circadian factor and homeostatic factor.

Before doing a through analysis, we must consider the four nervous systems present in our brain that regulates both wakefulness and sleep states: reticular activating system (RAS), hypothalamic sleep system, REM sleep sign generator and suprachiasmatic circadian clock. The reticular activating system (RAS) is the responsible of wakefulness state, depending on whether or not it is working, we will be awake or sleeping, respectively. The hypothalamic sleep system does the opposite process. It will be working during sleep hours and will stop working while we are awake. The circadian clock controls the two previous systems by activating the first one and inhibiting the second during daylight hours, and making the opposite procedure during the night. The REM sleep sign generator has the role of regulating REM and Non-REM sleep cycles, which we will discuss further.

Once we have talked about these systems, we can explain the three most important factors in the sleep. The vigilance factor activates the reticular activating system (RAS) by determining the wakefulness state even when we are really tired or in the dead of night. All anxiety and emergency reactions can be included in this factor, and also those substances such as caffeine and drugs that act by keeping active the reticular system. The circadian factor ensures that we respect the sleeping hours at nigh. This function is carried out by the circadian clock, which is located in the hypothalamic suprachiasmatic area. The homeostatic factor maintain a proper balance by increasing the need to sleep in the case we have been awake longer than usual.

Thus, if we find ourselves in a dark place, whether or not at night, without any kind of problem or thought, and after a hard day of work, the previous three factors will activate the hypothalamic sleep system and inhibit the reticular activatig system (RAS). This way, the threshold of external stimuli will be higher and we will fall asleep.

Let's talk about REM sleep. Does everybody know what I am talking about? I think so.

It is named REM sleep due to the fast movements of our eyes during this cycle. In fact, REM means Rapid Eye Movement. REM and Non-REM phases are alternated during the sleep state. Non-REM phase is made up of three stages: the fist one is a transition from wakefulness to sleep state where eye movements are slowed down and muscle tone is reduced. When a person is woken up during this stage, he/she is convinced of not having fallen asleep. It becomes difficult to wake up during the second stage, and even more difficult during the third stage since we enter in a deeper sleep where there is a lack of oniric activity or eye movements. The EEG pattern shows slow brainwaves, and blood pressure along with heart rate and cardiac output decrease substantially. After this last stage of Non-REM phase, we enter into REM phase, which is also called paradoxical sleep since the EEG pattern is similar to wakefulness state, although the sleep is as deep as in the third stage. In REM phase, our body experiences eye movements, muscle spasms, atony in the muscles that maintain an upright posture, and, at last, vivid dreams. So, we dream during REM phase.

Both REM and Non-REM phases are alternated while we are sleeping. A new REM phase occurs every 90-100 minutes, so during an eight-hour sleep period we will experience more than five REM phases and their respective dreams. However, we usually remember the last dream before waking up, which it is part of the last REM phase.

The sleep pattern varies considerably over the years and there are some modifications in REM and Non-REM phases length.

We already explained how we fall asleep and the different phases of sleep, but why do we sleep? Unfortunately, nobody has found a definitive answer so far. It is thought that it could be related to the memory consolidation and brain restoration, but why does sleep have such a determining role in every species? It is still a mystery.

Tuesday, September 3, 2013

Effects of nicotine on our brain

Nicotine is an active principle which is found in tobacco leaves. Its popularity is due to the effects this natural alkaloid produces in our brain.

Inside our body it exists different types of receptors that are activated once they bind to acetylcholine. There are two types of receptors: nicotinic receptors, which are also activated by nicotine, and muscarinic receptors, which are activated by muscarine, an alkaloid present in Amanita muscaria.

Nicotinic receptors can be found in the periphery, that is, in the postsynaptic membrane of skeletal muscle fibers, and in the central nervous system. The axon terminals of the neurons secrete acetylcholine, that binds to the postsynaptic membrane receptor. This causes the opening of cation channels, creating the depolarization of that neuron. As a result, peripheral receptors cause a muscle contraction and a nerve impulse is transmitted through depolarization by central receptors.

The amount of nicotine per cigarette (no more than 3 mg) is not enough to activate peripheral receptors of neuromuscular junction since a high concentration is needed, but they can bind to central nervous system receptors and activate or desensitize them (desactivate), depending on the dose. The effects of nicotine depend on the localization of these receptors.

Let us see the path of nicotine inside our body. The smoke of the cigarette goes inside our lungs, the nicotine reaches the pulmonary alveolus and it is absorbed into the bloodstream through the respiratory membrane. Once the nicotine is in the bloodstream, it substitutes the acetylcholine, acting on two principal neural systems where nicotine has a substantial effect on. These systems are: mesolimbic system and septo-hyppocampal system.

Mesolimbic system plays a fundamental role in dependence syndrome. Nicotine binds to the receptors of interneuron presynaptic membrane that inhibits the dopamine transmission of ventral tegmental area and desensitize them. This way, the inhibition of neurons which secrete dopamine gets interrupted and it creates an increase in this neurotransmitter. The release of dopamine stimulates the gratification and, therefore, the dependence. The continued exposure to nicotine increases the number of receptors at the level of inhibitory interneurons, creating the necessity of increasing even more the nicotine dose in order to get the initial gratification. The explanation is due to the amount of receptors which remain active is lower, and interneurons respond by increasing the number.

Septo-hyppocampal system is substantial in learning and memory abilities. Nicotine acts also at this level since this system is composed by cholinergic neurons that use the action of nicotinic receptors. All the effects of nicotine are not negative. If it is used in a moderate way, some learning and memory functions can be potentially stimulated, creating beneficial effects in our brain. This means that nicotine is not directly responsible for all the pathologies related to consumption of tobacco, but dependence. Moreover, dependence is the main cause of the immediate effects of tobacco because of the release of catecholamines in the bloodstream, such as the increase of heart rate and blood pressure.

Nicotine must be metabolized and eliminated from our body. The metabolization is carried out by a cytochrome P450 enzyme (CYP2A6). This is a polymorphous enzyme, its effects may vary depending on the person. Some people can metabolize nicotine faster than other. The degree of susceptibility to nicotine dependence will be higher or lower depending on the type of enzyme we have. Nicotine will remain much longer inside the body of a person with a slower metabolism, which means that this person won't need to consume nicotine for longer than someone with a faster metabolism.

Friday, August 30, 2013

Tetanus and Botulinum...How they act

We are used to hearing about tetanus and botulinum but, what are we really talking about? How do they act in our body?

Clostriudium tetani and Clostriudium botulinum are two types of anaerobic organisms which produce spores and are part of the Bacillaceae family. Their capacity of spore production make them possible to live even in the presence of oxygen. The effects of toxins can go unnoticed until they start producing two powerful neurotoxins capable of causing different sorts of neurological syndromes. Let us take a close look at the way these powerful toxins act in our body.

C. tetani spores can be found in the ground and can contaminate the wounds. When it exists a low presence of oxygen, especially with covered or infected wounds, the spores re-create the bacteria from which they have emerged by a process called germination. The bacteria is thereby active again and it can synthesize the neurotoxin. In this case it is called tetanospasmin. This toxin is produced as one single polypeptide, which is activated by an endopeptidase through a process called proteolysis and it creates two different fragments: a protein subunit α (light chain) and a protein subunit β (heavy chain), both joined by a disulfide bond. When tetanus toxin is located inside our body, the lymphatic vessels carry it through the nerve fibers. The toxin binds to the membrane of motor neurons α since it exists a correlation between heavy chain β and GM2 receptor, which is present in this type of neurons. Inside the neurons, the toxin is carried through the anterior horns of the spinal cord by using the dynein and then through the inhibitory interneurons via trans-synaptic. These have the function of inhibiting the motor neuron action by the release of inhibitory neurotransmitters. At this point it acts the protein subunit α, which contains zinc endopeptidase and are able to attack SNARE proteins necessary to release the neurotransmitters. As a result, there is a lack of inhibition of motor neurons, it causes a simultaneous spasm in agonist muscles and antagonists muscles (spastic paralysis) producing muscle rigidity and convulsions. This is called tetanus. The symptoms can occur within 4 to 15 days since the wound is created (incubation period). The most common symptom is called trismus, that is the contraction of the masseter muscle, since the distance to the facial nerves is shorter, thus causing the "Risus sardonicus". This contraction affects the muscles around and causes generalised muscle spasms which manifests as opisthotonus, an exaggerated contraction of muscles of the back. More than 90% of the patients without a treatment die and the main reason is the paralysis of muscles of respiration.

There is a similar bacteria called C. botulinum, which was named after the latin word for sausage, botulus since most of the cases of botulism are transmitted by consumption of contaminated food. This bacteria can be present either in ground or water. There are seven types of botulinum toxin (identified from letter A to G). Nevertheless, the human being is just susceptible to types A, B, E and F. The toxin A is the strongest poison of the world, 70 µg of toxin A are enough to kill a person weighing 70 kg. This toxin consists of a light chain α and a heavy chain β, like the rest of the toxins, and its action mechanism is similar to the tetanus toxin. The spores grow under anaerobiosis, especially in preserved food, where the toxin is produced and goes inside our body by the consumption of this food. The chain β protects the neurotoxin from the stomach acidity, the intestine absorbs it and then is carried by the blood through the nerve endings where acetylcholine is inhibited without going all the way back to the spinal cord, like C. tetani does.

Acetylcholine is an important neurotransmitter for muscle contraction, and without it there is an alteration of contractions which produces flaccid paralysis.

The effects of this toxin can be noticed within a couple of days after the consumption of contaminated food. The muscles become weaker and it causes respiratory muscle paralysis and, therefore, the death.

This disease can be prevented by avoiding the growth of spores in the food. In order to do so, the food pH must been acid or the temperature food must been maintained at 4º C (39.2º F) or lower. The food can also be heated up to 100º C (212º F) for 10 minutes in order to destroy the toxin.

The botulinum toxin is used as a local therapy to treat some disorders such as migraine, asthma, achalasia or even expression lines between eyebrows. These expression lines, spasms or twitches can be avoided through the flaccid paralysis of facial muscles.