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Neurochemistry is the study of chemicals, including neurotransmitters and other molecules such as psychopharmaceuticals and neuropeptides, that control and influence the physiology of the nervous system. This particular field within neuroscience examines how neurochemicals influence the operation of neurons, synapses, and neural networks. Neurochemists analyze the biochemistry and molecular biology of organic compounds in the nervous system, and their roles in such neural processes including cortical plasticity, neurogenesis, and neural differentiation.



While neurochemistry as a recognized science is relatively new, the idea behind neurochemistry has been around since the 18th century. Originally, the brain had been thought to be a separate entity apart from the peripheral nervous system. Beginning in 1856, there was a string of research that refuted that idea. The chemical makeup of the brain was nearly identical to the makeup of the peripheral nervous system. [1] The first large leap forward in the study of neurochemistry came from Johann Ludwig Wilhelm Thudichum, who is one of the pioneers in the field of "brain chemistry." He was one of the first to hypothesize that many neurological illnesses could be attributed to an imbalance of chemicals in the brain. He was also one of the first scientists to believe that through chemical means, the vast majority of neurological diseases could be treated, if not cured. [2]

Irvine Page (1901-1991) was an American psychologist that published the first major textbook focusing on neurochemistry in 1937. He had also established the first department that was solely devoted to the study of neurochemistry in 1928 at the Munich Kaiser Wilhelm Institute for Psychiatry. [3]

Back in the 1930s, neurochemistry was mostly referred to as "brain chemistry" and was mostly devoted to finding different chemical species without directly proposing their specific roles and functions in the nervous system. The first biochemical pathology test for any brain disease can be attributed to Maria Buscaino (1887-1978), a neuropsychiatrist who studied schizophrenia. She found that treating her patients' urine who had schizophrenia, extrapyramidal disorders, or amentia, with 5% silver nitrate produced a black precipitate linked with an abnormal level of amines. This became known as the "Buscaino Reaction." [3]

In the 1950s, neurochemistry became a recognized scientific research discipline. [4] The founding of neurochemistry as a discipline traces its origins to a series of "International Neurochemical Symposia", of which the first symposium volume published in 1954 was titled Biochemistry of the Developing Nervous System. [5] These meetings led to the formation of the International Society for Neurochemistry and the American Society for Neurochemistry. These early gatherings discussed the tentative nature of possible neurotransmitter substances such as acetylcholine, histamine, substance P, and serotonin. By 1972, ideas were more concrete.

One of the first major successes in using chemicals to alter brain function was the L-DOPA experiment. In 1961, Walter Burkmayer injected L-DOPA into a patient with Parkinson's disease. Shortly after injection, the patient had a drastic reduction in tremors, and they were able to control their muscles in ways they hadn't been able to in a long time. The effect peaked within 2.5 hours and lasted approximately 24 hours. [1]

Neurotransmitters and neuropeptides

The most important aspect of neurochemistry is the neurotransmitters and neuropeptides that comprise the chemical activity in the nervous system. There are many neurochemicals that are integral for proper neural functioning.

The neuropeptide oxytocin, synthesized in magnocellular neurosecretory cells, plays an important role in maternal behavior and sexual reproduction, particularly before and after birth. It is a precursor protein that is processed proteolytically to activate the neuropeptide as its shorter form. It is involved in the letdown reflex when mothers breastfeed, uterine contractions, and the hypothalamic-pituitary-adrenal axis where oxytocin inhibits the release of cortisol and adrenocorticotropic hormone. [6] [7] [8] [9]

Glutamate, which is the most abundant neurotransmitter, is an excitatory neurochemical, meaning that its release in the synaptic cleft causes the firing of an action potential. GABA, or Gamma-aminobutyric acid, is an inhibitory neurotransmitter. It binds to the plasma membrane in the synapses of neurons, triggering the influx of negatively charged chloride ions and the efflux of positively charged potassium ions. This exchange of ions leads to the hyperpolarization of the transmembrane potential of the neuron, which is caused by this negative change. [10] [11]

Dopamine is a neurotransmitter with much importance in the limbic system which regulates emotional function regulation. Dopamine has many roles in the brain including cognition, sleep, mood, milk production, movement, motivation, and reward. [12]

Serotonin is a neurotransmitter that regulates mood, sleep, and other roles of the brain. It is a peripheral signal mediator and is found in the gastrointestinal tract as well as in blood. Research also suggests that serotonin may play an important role in liver regeneration. [13]

Neurotypical neurochemistry

Neurochemistry is the study of the different types, structures, and functions of neurons and their chemical components. Chemical signaling between neurons is mediated by neurotransmitters, neuropeptides, hormones, neuromodulators, and many other types of signaling molecules. Many neurological diseases arise due to an imbalance in the brain's neurochemistry. For example, in Parkinson's Disease, there is an imbalance in the brain's level of dopamine. Medications include neurochemicals that are used to alter brain function and treat disorders of the brain. A typical neurochemist might study how the chemical components of the brain interact, neural plasticity, neural development, physical changes in the brain during disease, and changes in the brain during aging. [14] [15]

Neurochemistry of PTSD

One of the major areas of research within neurochemistry is looking at how post-traumatic stress disorder alters the brain. Neurotransmitter level fluctuations can dictate whether a PTSD episode occurs and how long the episode lasts. Dopamine has less of an effect than norepinephrine. Different neurochemicals can affect different parts of the brain. This allows drugs to be used for PTSD to not have an undesired effect on other brain processes. An effective medication to help alleviate nightmares associated with PTSD is Prazosin. [16]

See also

Related Research Articles

<span class="mw-page-title-main">Neuron</span> Electrically excitable cell that communicates via synapses

A neuron, neurone, or nerve cell is an electrically excitable cell that communicates with other cells via specialized connections called synapses. The neuron is the main component of nervous tissue in all animals except sponges and placozoa. Non-animals like plants and fungi do not have nerve cells.

<span class="mw-page-title-main">Neurotransmitter</span> Chemical substance that enables neurotransmission

A neurotransmitter is a signaling molecule secreted by a neuron to affect another cell across a synapse. The cell receiving the signal, any main body part or target cell, may be another neuron, but could also be a gland or muscle cell.

<span class="mw-page-title-main">Psychopharmacology</span> Study of the effects of psychoactive drugs

Psychopharmacology is the scientific study of the effects drugs have on mood, sensation, thinking, and behavior. It is distinguished from neuropsychopharmacology, which emphasizes the correlation between drug-induced changes in the functioning of cells in the nervous system and changes in consciousness and behavior.

<span class="mw-page-title-main">Substantia nigra</span> Structure in the basal ganglia of the brain

The substantia nigra (SN) is a basal ganglia structure located in the midbrain that plays an important role in reward and movement. Substantia nigra is Latin for "black substance", reflecting the fact that parts of the substantia nigra appear darker than neighboring areas due to high levels of neuromelanin in dopaminergic neurons. Parkinson's disease is characterized by the loss of dopaminergic neurons in the substantia nigra pars compacta.

<span class="mw-page-title-main">Enteric nervous system</span> Vital system controlling the gastrointestinal tract

The enteric nervous system (ENS) or intrinsic nervous system is one of the main divisions of the autonomic nervous system (ANS) and consists of a mesh-like system of neurons that governs the function of the gastrointestinal tract. It is capable of acting independently of the sympathetic and parasympathetic nervous systems, although it may be influenced by them. The ENS is nicknamed the "second brain". It is derived from neural crest cells.

<span class="mw-page-title-main">Monoamine neurotransmitter</span> Monoamine that acts as a neurotransmitter or neuromodulator

Monoamine neurotransmitters are neurotransmitters and neuromodulators that contain one amino group connected to an aromatic ring by a two-carbon chain (such as -CH2-CH2-). Examples are dopamine, norepinephrine and serotonin.

<span class="mw-page-title-main">Monoamine transporter</span>

Monoamine transporters (MATs) are protein structures that function as integral plasma-membrane transporters to regulate concentrations of extracellular monoamine neurotransmitters. Three major classes of MATs are responsible for the reuptake of their associated amine neurotransmitters. MATs are located just outside the synaptic cleft (peri-synaptically), transporting monoamine transmitter overflow from the synaptic cleft back to the cytoplasm of the pre-synaptic neuron. MAT regulation generally occurs through protein phosphorylation and posttranslational modification. Due to their significance in neuronal signaling, MATs are commonly associated with drugs used to treat mental disorders as well as recreational drugs. Compounds targeting MATs range from medications such as the wide variety of tricyclic antidepressants, selective serotonin reuptake inhibitors such as fluoxetine (Prozac) to stimulant medications such as methylphenidate (Ritalin) and amphetamine in its many forms and derivatives methamphetamine (Desoxyn) and lisdexamfetamine (Vyvanse). Furthermore, drugs such as MDMA and natural alkaloids such as cocaine exert their effects in part by their interaction with MATs, by blocking the transporters from mopping up dopamine, serotonin, and other neurotransmitters from the synapse.

A neurochemical is a small organic molecule or peptide that participates in neural activity. The science of neurochemistry studies the functions of neurochemicals.

<span class="mw-page-title-main">Excitatory synapse</span> Sort of synapse

An excitatory synapse is a synapse in which an action potential in a presynaptic neuron increases the probability of an action potential occurring in a postsynaptic cell. Neurons form networks through which nerve impulses travel, each neuron often making numerous connections with other cells. These electrical signals may be excitatory or inhibitory, and, if the total of excitatory influences exceeds that of the inhibitory influences, the neuron will generate a new action potential at its axon hillock, thus transmitting the information to yet another cell.

<span class="mw-page-title-main">Arcuate nucleus</span>

The arcuate nucleus of the hypothalamus is an aggregation of neurons in the mediobasal hypothalamus, adjacent to the third ventricle and the median eminence. The arcuate nucleus includes several important and diverse populations of neurons that help mediate different neuroendocrine and physiological functions, including neuroendocrine neurons, centrally projecting neurons, and astrocytes. The populations of neurons found in the arcuate nucleus are based on the hormones they secrete or interact with and are responsible for hypothalamic function, such as regulating hormones released from the pituitary gland or secreting their own hormones. Neurons in this region are also responsible for integrating information and providing inputs to other nuclei in the hypothalamus or inputs to areas outside this region of the brain. These neurons, generated from the ventral part of the periventricular epithelium during embryonic development, locate dorsally in the hypothalamus, becoming part of the ventromedial hypothalamic region. The function of the arcuate nucleus relies on its diversity of neurons, but its central role is involved in homeostasis. The arcuate nucleus provides many physiological roles involved in feeding, metabolism, fertility, and cardiovascular regulation.

<span class="mw-page-title-main">Neuropeptide</span> Peptides released by neurons as intercellular messengers

Neuropeptides are chemical messengers made up of small chains of amino acids that are synthesized and released by neurons. Neuropeptides typically bind to G protein-coupled receptors (GPCRs) to modulate neural activity and other tissues like the gut, muscles, and heart.

Neuropharmacology is the study of how drugs affect cellular function in the nervous system, and the neural mechanisms through which they influence behavior. There are two main branches of neuropharmacology: behavioral and molecular. Behavioral neuropharmacology focuses on the study of how drugs affect human behavior (neuropsychopharmacology), including the study of how drug dependence and addiction affect the human brain. Molecular neuropharmacology involves the study of neurons and their neurochemical interactions, with the overall goal of developing drugs that have beneficial effects on neurological function. Both of these fields are closely connected, since both are concerned with the interactions of neurotransmitters, neuropeptides, neurohormones, neuromodulators, enzymes, second messengers, co-transporters, ion channels, and receptor proteins in the central and peripheral nervous systems. Studying these interactions, researchers are developing drugs to treat many different neurological disorders, including pain, neurodegenerative diseases such as Parkinson's disease and Alzheimer's disease, psychological disorders, addiction, and many others.

Hypokinesia is one of the classifications of movement disorders, and refers to decreased bodily movement. Hypokinesia is characterized by a partial or complete loss of muscle movement due to a disruption in the basal ganglia. Hypokinesia is a symptom of Parkinson's disease shown as muscle rigidity and an inability to produce movement. It is also associated with mental health disorders and prolonged inactivity due to illness, amongst other diseases.

Neuropsychopharmacology, an interdisciplinary science related to psychopharmacology and fundamental neuroscience, is the study of the neural mechanisms that drugs act upon to influence behavior. It entails research of mechanisms of neuropathology, pharmacodynamics, psychiatric illness, and states of consciousness. These studies are instigated at the detailed level involving neurotransmission/receptor activity, bio-chemical processes, and neural circuitry. Neuropsychopharmacology supersedes psychopharmacology in the areas of "how" and "why", and additionally addresses other issues of brain function. Accordingly, the clinical aspect of the field includes psychiatric (psychoactive) as well as neurologic (non-psychoactive) pharmacology-based treatments. Developments in neuropsychopharmacology may directly impact the studies of anxiety disorders, affective disorders, psychotic disorders, degenerative disorders, eating behavior, and sleep behavior.

Neuromodulation is the physiological process by which a given neuron uses one or more chemicals to regulate diverse populations of neurons. Neuromodulators typically bind to metabotropic, G-protein coupled receptors (GPCRs) to initiate a second messenger signaling cascade that induces a broad, long-lasting signal. This modulation can last for hundreds of milliseconds to several minutes. Some of the effects of neuromodulators include: alter intrinsic firing activity, increase or decrease voltage-dependent currents, alter synaptic efficacy, increase bursting activity and reconfiguration of synaptic connectivity.

<span class="mw-page-title-main">Clinical neurochemistry</span>

Clinical neurochemistry is the field of neurological biochemistry which relates biochemical phenomena to clinical symptomatic manifestations in humans. While neurochemistry is mostly associated with the effects of neurotransmitters and similarly functioning chemicals on neurons themselves, clinical neurochemistry relates these phenomena to system-wide symptoms. Clinical neurochemistry is related to neurogenesis, neuromodulation, neuroplasticity, neuroendocrinology, and neuroimmunology in the context of associating neurological findings at both lower and higher level organismal functions.

<span class="mw-page-title-main">Gut–brain axis</span> Biochemical signaling between the gastrointestinal tract and the central nervous system

The gut–brain axis is the two-way biochemical signaling that takes place between the gastrointestinal tract and the central nervous system (CNS). The term "gut–brain axis" is occasionally used to refer to the role of the gut microbiota in the interplay as well. The "microbiota–gut–brainaxis" explicitly includes the role of gut microbiota in the biochemical signaling events that take place between the GI tract and the CNS. Broadly defined, the gut–brain axis includes the central nervous system, neuroendocrine system, neuroimmune systems, the hypothalamic–pituitary–adrenal axis, sympathetic and parasympathetic arms of the autonomic nervous system, the enteric nervous system, vagus nerve, and the gut microbiota.

Central nervous system fatigue, or central fatigue, is a form of fatigue that is associated with changes in the synaptic concentration of neurotransmitters within the central nervous system which affects exercise performance and muscle function and cannot be explained by peripheral factors that affect muscle function. In healthy individuals, central fatigue can occur from prolonged exercise and is associated with neurochemical changes in the brain, primarily involving serotonin (5-HT), noradrenaline, and dopamine. Central fatigue plays an important role in endurance sports and also highlights the importance of proper nutrition in endurance athletes.

Functional Ensemble of Temperament (FET) is a neurochemical model suggesting specific functional roles of main neurotransmitter systems in the regulation of behaviour.

Fernando Garcia de Mello is a renowned neurochemist from Brazil. He obtained his degree in Biochemistry in 1968 from the State University of Rio de Janeiro. Fernando Mello started his scientific training as an undergraduate student at the Brazilian National Institute of Cancer, and later at the Institute of Biophysics from the Federal University of Rio de Janeiro, being mentored by dr. Firmino de Castro, which greatly influenced him to have a more humanistic approach towards the students that he would train. It was only during his post-doc period (1973-1976) at the National Institutes of Health under supervision of dr. Marshall Warren Nirenberg that Mello began his research in Neurochemistry, using the embryonary Retina as a model for his investigations.


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