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*Corresponding Author: Arpita Doshi, Innovator & Founder of Nutrition Dynamic Foods LLP, Ahmedabad – Gujarat, India.
Citation: Arpita Doshi, (2022). Role of Stress and Inflammation on Neurotransmission affecting Signalling release of Dietary Acetylcholine, Role of Serotonin to Induce Normal Sleep Cycle. J. Clinical Research Notes. 3(3); DOI: 10.31579/2690-8816/064
Copyright: © 2022 Arpita Doshi, this is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.
Received: 22 March 2022 | Accepted: 04 April 2022 | Published: 22 April 2022
Keywords: mental health; brain, neurotransmitters; acetylcholine; serotonin; sleep; diet composition; quality nutrition; gut brain axis; hypothalamus pituitary adrenal axis
Mental health has seen to apprehend the burden on national healthcare after escalating event like COVID where need for awareness, understanding its role in behaviour and medical care requirements surged. However, socioeconomic disparity, stress of lockdown, work from home, traumatic brain injury happening due to death and fear accelerated the need to focus on mental wellness. The burden of Mental diseases has almost doubled since 1990, and the uncertainty to predictthe growth rate prevails. Stress has been a major activator factor to increasethe burden of all inflammatory response happening at cellular level as stress affects our Hypothalamus-Pituitary- Adrenal Axis and Gut-Brain Axis [2]. Inflammation has become major cause in disturbing our cellular gradient potentiality, membrane permeability and thereby causing disruptions in major signalling biochemical pathways which affectour thought process,dietary choices and overall wellbeing.
Exposure to radiations, chemical toxins, inhaling polluted air, dependence on convenience foods and lack of physical activity are few major contributing factors that are affecting our secondary chemical metabolites resulting in primary damage of our cellular membrane. Acetylcholine a neurotransmitter is highly affected with cellular gradient disturbances thereby affecting our nervous system and overall behaviour of our body. Serotonin a neurotransmitter to induce sleep is hampered due to insufficient tryptophan content in our diet and inability to digest tryptophan rich foods due to gradient and electrochemical chargesimbalances happening at our membranelevels. Through this article an attempt has been made to simplify the understanding of stress and inflammation on primary function of tissue membrane in energy and metabolism which initiates a series of secondary biochemical chain reactions.
According to a survey 792 million people were suffering with some mental illness and most common prevailing are anxiety and depression. Contributing factors were socioeconomic disparity, inequality, lack of education, unhygienic living conditions, nutrient deficit diet. Our internal biochemical pathways are highly sensitive towards quality of what we think, breathe and consume on daily basis. The adverse effects of our ill health care been heightened when we enter our 30s due to work and financial pressure which affects our neurotransmission and signaling pathways. Stress is defined as an absolute response that is generated in our Central Nervous System (CNS) and distributed using our neurotransmission network throughout the body which is regulated by secretion and diffusion process. Many external factors like infection, pollution, unhygienic conditions and foods have played major role in disturbing our inner metabolic environment resulting into inflammatory responses (headaches, acidity and bloating), changed behavior (depression, anxiety, hypersensitivity), dietary preferences (cravings, unbalanced proportion, junk foods over healthy foods), are few observable changes that we have witnessedmore especially post pandemic. Many scientists and researchers are presently working to find a concrete solution either drugs, tools or foods that can help in preventing inflammatory responses generated due to unhealthy eating habits, however as many biochemical processes like membrane permeability, gradient imbalances, genetics, metabolic rate and metabolic compounds are compromised during inflammatory responses. Two parallel axis namely Hypothalamus-Pituitary-Adrenal Axis and Gut-Brain Axis that determines our anatomical and physiological performances creates a resonating chain reactions under stress and inflammatory responses.
Inflammation and Tissue Injury
When any viral, bacterial, chemical, heat, trauma affects and damages our tissue in any stressful events numerous substances are released that brings in secondary changes to the adjacent undamaged tissues, the process is termed as Inflammation [1]. Characteristics of Inflammation includes 1) Vasodilation of blood vessels(excess blood flow) 2)Increase permeability of capillaries causing chemical membrane gradient imbalance 3)Fluid clots are generated due to interaction with fibrinogen and other proteins from the leaking capillaries 4)Migration of granulocytes and monocytes into tissue 5)Swelling of the tissue [1]. The chemical substances produced due to tissue damage and cause the above reactions are histamine, bradykinin, serotonin, prostaglandins, plasma proteins, lymphokines, these together activate, and they initiate the tissue macrophage system our body’s first defence system against infection [1]. The phagocytic action of macrophages begins within few minutes of inflammation depending on the site of inflammation like histiocytes in subcutaneous tissues, alveolar in lungs and microglia in the brain.[1] Based on the invading neutrophil and its adhesion molecules second line of defence is initiated within an hour of infection where pool of neutrophils begin their scavenging activity.[1] When the neutrophilia condition is attained monocytes from the blood enters the inflamed tissue and activates second macrophage invasionprocess which is the thirdline of defence. [1] Lastly increase production of granulocytes and monocytes by bone marrow if continued as stimulus from the inflamed tissue the process lasts for months and years resulting in non-healing conditions. During this defence activation period control chemicals like tumor necrosis factor(TNF), interleukin-1(IL-1), granulocyte-monocyte colony- stimulating factor(GM-CSF) and monocyte colony stimulating factor (M-CSF) are formed that combines to proceed the formation of white blood cells that helps in eliminating the cause of inflammation.
Role of Stress on Central Nervous System
Stress has become an inevitable process in today’s lifestyle and pandemic was a catalyst to this process where stress is defined as absolute responseto any claimed change that body experiences. The HPA axis and Sympathetic Nervous System (SNS) are the peripheral limbs of stress which are activated inside the brain and are transported to lymphatic system through neurons and neurotransmitters [2]. Nervous system is highly complex messenger network system that controls our thinking process and actions resulting from our thought process. Cell membranes comprisesof positive charge and negativecharge, nerves and musclecells membranes are involved in rapid electrochemical impulse generation that are used to transmit our signals, however during stressful conditions the diffusion potentials at cell membrane is disturbed due to which nerve action potential is hampered.
Neuromuscular junctions contain proteins named acetylcholine that are released in synaptic space when nerve impulse passes by.[1]
DietaryAcetylcholine (ACh):
Acetylcholine was first discovered in 1914 by Ewins in non-animal cells and since then many scientists started researching on its role in plant metabolism. In 1966 Cumming and Wagner first time noted that in plants just like animals, bioelectric potentials arose in response to light stimuli.[3]. Table 1 indicates Acetylcholine occurrence in higher plants (ACh). The chemical formula of Acetylcholine is (CH3COOCH2CH2N+(CH3)3) and its molecular mass is 146.2 and is highlydependent on the pH level. The stability of ACh solutions decrease with increase in pH levels and in basic solutions the substance hydrolysis rapidly to choline and acetic acid.[3] Thus ACh is highly sensitive to pH and also it was noted that at temperature 25oC and pH7.0 decomposition takes place in about 20days but at pH12 it only takes 12seconds, indicating that along with pHtemperature also plays vital role in decomposition of ACh.[3]
The Central Nervous System (CNS) contains more than 100billion neurons which receives millions of bits of information from different sensory nerves and organs that are integrated and determines responses to be made by the body.[1] Fig. 2 shows the structure of neuron with its important functional parts
Most of the information that our brain receives through neurons are generated from sensory excited receptors like eyes, ears, smell and touch. These experiences determine our response reactions to happeninstantly or storein memory for minutes,weeks and years.The motor functions of the body are controlled by contraction of skeletal muscle, smooth muscle guarding internal organs and secretion of hormones in exocrine and endocrine glands in the body. CNS main role is processing the information by balancing sensory and motor receptors through synapses (Synapses is the junction point from one neuron to next)i.e. synapses determines the direction of the nervous signals and are controlled by inhibitory and facilitatory signals from other areas of CNS. There are two types of synapses 1) Chemical and 2) Electrical most of all the synapse uses chemical synapses that release neurotransmitters which acts on receptor proteins in the membrane. More then 40 neurotransmitters have been identified but widely explored ones are Acetylcholine, Norepinephrine, Epinepherine, Histamine, Gamma-aminobutyricacid (GABA), Glycine,Serotonine and Glutamate.
Electric synapses are characterised by direct open fluid channels that conduct electricity from one cell to next and are made up of small tubular protein structures called “Gap Junctions” [1]. Fig. 3 depicts the somatosensory response generated from the excited sensory receptors throughout the body.
Traumatic Brain Injury:
Trauma is defined as emotional response generated due to accident, physical abuse, death or natural disasters. Traumatic Brain Injury is defined as damaged caused by external forces like violent blow, bump or blast that damages our brains protective capacity.[4] Based on the damage TBI can be classified as Mild, Moderate or Severe and the effect can be temporarily, few days, weeks, months or lifetime. Clinical symptoms of TBI are headaches, dizziness, nausea, fatigue, sleep disruptions, hearing and visual disturbances.[4] TBI is classified as primarily that affects the cognitivefunctionality namely attentiondeficient, memory problemsand white matter diffusion while secondary injury affects the behavioural patterns like irritability, mood swings, aggressive, impulsive and self-centred behaviour. Apart from cognitive and behavioural disruption also neuroinflammatory responses increases the chances of neurodegenerative diseases like Schizophrenia, Parkinson, Alzheimer’s, Dementia which are often found in females due to dysfunction of motor nervous system, older adults due to low socioeconomic status. The moment TBI impacts a chain reaction from primary injury activates the secondary chemical avalanche resulting in disruption in blood- brain-barrier (BBB)(Neuronal cell death), oxidative stress(accumulation of Reactive oxygen species(ROS) and reactive nitrogen species(RON)), mitochondrial dysfunction, excitotoxicity(accumulation of intracellular glutamateto extracellular space) and inflammation.[4]
Importance of Sleep:
Sleep is defined as unconscious state of body that can be brought to conscious state by sensory stimuli. It is a passive process associated with amplitude of brain activation. Functionality of sleep isto bring restorative, homeostatic function and normalized thermoregulation and energy conservation.[5] There are two physiological state of sleep 1) Non-Rapid Eye Movement (NREM) 2) Rapid Eye Movement (REM). In order to understand the two types of sleep and the function of brain an electroencephalogram helps in better understanding and Fig. 4 shows an electroencephalogram patterns of stages of human sleep and wakefulness followed by Table 2 depicting electrophysiological criteria.
NREM | REM |
Peaceful state with dreams that arelucid and purposeful | Near to awake state withdreams that are abstract andbizarre |
Pulse rate, Respiration rate, Bloodpressure is low | Pulse rate, Respiration rate, Blood pressure is high alongwith high brainoxygen requirement |
Resting muscle potential is low | Near to total paralysis of skeletal(postural) muscles |
Hemothermic Regulation | Thermoregulation altered |
Dietary Sources of Tryptophan Precurssor of Serotonin:
Serotonin (5-hydroxytryptamine, 5-HT) is an important neurotransmitter synthesized by very limited number of cells in brainstem raphe nuclei. The physiological role of 5-HT as CNS modulator has been obstructed due to diversification of serotonergic receptorsand its transmission which is mostly paracrine in nature.[6] The synthesis of brain 5-HT synthesis rate is physiologically regulated by substrate l-tryptophan(Trp) levels with enzyme Tryptophan hydroxylase(TPH)2 acting as rate limiting enzyme. An experiment on rats conducted by Ogiso E.,et.al[6] in 2012 strongly suggested that 5-HT has a significant role on circadian rhythm of sleep-wake cycles. Tryptophan is an amino acid that is crucially obtained from dietary sources and is metabolised intracellularly in different tissues to perform numerous physiological functions. It is found circulating in plasma and blood with its binding protein albumin, however free form of tryptophan content is just 10-12% and many drugs or fatty acids have shown to modify binding of tryptophan to albumin.[7] There are two types of tryptophan L-Tryptophan produced during food processing and D-Tryptophan produced by gut microbiome.[8] Degradation of tryptophan into kynurenine in presence of Indoleamine2,3dioxygenase in immune cells plays vital role during infections, inflammations and preganancy.[7] In order to understand the bioavailability of tryptophan that can enter the complexprotein metabolism pathway numerous analytical methods were proposed to understand optimal pH and temperature requirement. Many research has shown that protein hydrolysates are beneficiary during tissue repair mechanism due to its increase absorption ability based on which tryptophan hydrolysates are widely used in dietary supplements and food fortification industries. Fig. 5 shows common cereals and millets along with grain and legumes that contain tryptophan.[12] The RDA of tryptophan is in between 250mg – 425mg/day which means dietary intake of 3.6-6.0mg/kg of the body weight.[13] The article also mentions that hydroslyte form of tryptophan has better absorption functionality pure tryptophan.[7]
FutureWork:Thus, as observed inflammatory response that are created due to tissue injury, infection or toxic chemical ingestion are the primary cause of overall health damage. Most of the diseases that are engulfing presently are causing harmful effect on our tissue membrane which disturbs our haemostasis, cause inflammation of the cell and are remodelling our tissue repair process that creates a challenging tasks for drug formulation. Study on rodentswas conducted by[9] that showedhow toxicokinetics and toxicodynamics follows the same rule of absorption, distribution, metabolism and excretionthat interfers with our signalling pathways, growth factorsand hormone secretion.
This study also showed how nutrients like protein, carbohydrates and lipids affects the toxic responses generated and affecting our energy metabolism at cellular levels. Another study was conducted on membrane composition that indicated that manipulation of membrane composition depending on size of the body molecular activity of membrane proteins are also affected.[10] Thus much work on role of nutrition, inflammatory genes suppression, toxin evaluation needs to be conducted based on geographic, demographic, socioeconomic differences which can help in future design of some novel functional foods that can bring a communicating pathway to communicate with all inflammatory non communicable diseases.
There are no conflicts of interest.
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