Neurochemistry

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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.

Contents

History

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 Vito Maria Buscaino (1887-1978), a neuropsychiatrist who studied schizophrenia. He 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 found in the nervous system of animals

A neuron, neurone, or nerve cell is an excitable cell that fires electric signals called action potentials across a neural network in the nervous system. Neurons communicate with other cells via synapses, which are specialized connections that commonly use minute amounts of chemical neurotransmitters to pass the electric signal from the presynaptic neuron to the target cell through the synaptic gap.

<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, 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, behavior, judgment and evaluation, and memory. 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">Enteric nervous system</span> Vital system controlling the gastrointestinal tract

The enteric nervous system (ENS) or intrinsic nervous system is one of the three main divisions of the autonomic nervous system (ANS), the other being the sympathetic (SNS) and parasympathetic nervous system (PSNS), 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 SNS and PSNS, 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.

The following outline is provided as an overview of and topical guide to neuroscience:

<span class="mw-page-title-main">Monoamine transporter</span> Proteins that function as integral plasma-membrane transporters

Monoamine transporters (MATs) are proteins that function as integral plasma-membrane transporters to regulate concentrations of extracellular monoamine neurotransmitters. The three major classes are serotonin transporters (SERTs), dopamine transporters (DATs), and norepinephrine transporters (NETs) and 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 post-translational 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 travels, each neuron often making numerous connections with other cells of neurons. 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">Dopaminergic pathways</span> Projection neurons in the brain that synthesize and release dopamine

Dopaminergic pathways in the human brain are involved in both physiological and behavioral processes including movement, cognition, executive functions, reward, motivation, and neuroendocrine control. Each pathway is a set of projection neurons, consisting of individual dopaminergic neurons.

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

The arcuate nucleus of the hypothalamus (ARH), or ARC, is also known as the infundibular nucleus to distinguish it from the arcuate nucleus of the medulla oblongata in the brainstem. The arcuate nucleus 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 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.

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.

<span class="mw-page-title-main">Neuromodulation</span> Regulation of neurons by neurotransmitters

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 altering intrinsic firing activity, increasing or decreasing voltage-dependent currents, altering synaptic efficacy, increasing bursting activity and reconfiguring synaptic connectivity.

<span class="mw-page-title-main">Synapse</span> Structure connecting neurons in the nervous system

In the nervous system, a synapse is a structure that permits a neuron to pass an electrical or chemical signal to another neuron or to the target effector cell. Synapses can be chemical or electrical. In case of electrical synapses, neurons are coupled bidirectionally in continuous-time to each other and are known to produce synchronous network activity in the brain. As such, signal directionality cannot always be defined across electrical synapses.

<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 "microbiota–gut–brain axis" highlights the role of gut microbiota in these biochemical signaling. 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.

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.

References

  1. 1 2 Foley, P. (2007). "Succi nervorum: A brief history of neurochemistry". Neuropsychiatric Disorders an Integrative Approach. Journal of Neural Transmission. Supplementa. Vol. 72. Springer Vienna. pp. 5–15. doi:10.1007/978-3-211-73574-9_2. ISBN   9783211735732. PMID   17982872.{{cite book}}: |journal= ignored (help)
  2. ↑ Thudichum, J. L. W. (1962). A treatise on the chemical constitution of the brain. Archon Books. OCLC   1030309150.
  3. 1 2 Boullerne, Anne I.; Foley, Paul; Turner, Anthony J.; Johnston, Graham A.R.; Beart, Philip M. (January 2020). "The origins and early history of neurochemistry and its societies". Journal of Neurochemistry. 152 (1): 8–28. doi: 10.1111/jnc.14839 . hdl: 11343/286491 . ISSN   0022-3042. PMID   31357242.
  4. ↑ Agranoff, Bernard W. (22 July 2003). "History of Neurochemistry". eLS. doi:10.1038/npg.els.0003465. ISBN   978-0470016176.{{cite book}}: |journal= ignored (help)
  5. ↑ Siegel, George J.; Albers, R.W.; Brady, S.T.; Price, D.L. (2006). Basic Neurochemistry, 7th Ed. Academic Press. ISBN   978-0-12-088397-4.
  6. ↑ Lee, Heon-Jin; Macbeth, Abbe H.; Pagani, Jerome; Young, W. Scott (2009-04-10). "Oxytocin: The Great Facilitator of Life". Progress in Neurobiology. 88 (2): 127–151. doi:10.1016/j.pneurobio.2009.04.001. ISSN   0301-0082. PMC   2689929 . PMID   19482229.
  7. ↑ "Human Milk and Lactation" . Medscape. 2022-03-15.
  8. ↑ Takayanagi, Yuki; Yoshida, Masahide; Bielsky, Isadora F.; Ross, Heather E.; Kawamata, Masaki; Onaka, Tatsushi; Yanagisawa, Teruyuki; Kimura, Tadashi; Matzuk, Martin M.; Young, Larry J.; Nishimori, Katsuhiko (2005-10-25). "Pervasive social deficits, but normal parturition, in oxytocin receptor-deficient mice". Proceedings of the National Academy of Sciences. 102 (44): 16096–16101. Bibcode:2005PNAS..10216096T. doi: 10.1073/pnas.0505312102 . ISSN   0027-8424. PMC   1276060 . PMID   16249339.
  9. ↑ Siebielec, Sylwia; Siebielec, Grzegorz; Samolińska, Wioletta (2018-06-30). "The content of lead and cadmium in selected vegetables in the Lublin region". Nauka Przyroda Technologie. 12 (2). doi: 10.17306/j.npt.00237 . ISSN   1897-7820. S2CID   92547848.
  10. ↑ Sapolsky, Robert. "Biology and Human Behavior: The Neurological Origins of Individuality, 2nd Edition". PsycEXTRA Dataset. doi:10.1037/e526622012-001 . Retrieved 2022-04-29.
  11. ↑ Majumdar, Devashis; Guha, Sephali (November 1988). "Conformation, electrostatic potential and pharmacophoric pattern of GABA (gamma-aminobutyric acid) and several GABA inhibitors". Journal of Molecular Structure: THEOCHEM. 180: 125–140. doi:10.1016/0166-1280(88)80084-8.
  12. ↑ Benes, Francine M (January 2001). "Carlsson and the discovery of dopamine". Trends in Pharmacological Sciences. 22 (1): 46–47. doi:10.1016/s0165-6147(00)01607-2. ISSN   0165-6147. PMID   11165672.
  13. ↑ George J. Siegel; et al., eds. (2006). Basic neurochemistry: molecular, cellular and medical aspects (7th ed.). Amsterdam. ISBN   978-0-08-047207-2. OCLC   123438340.{{cite book}}: CS1 maint: location missing publisher (link)
  14. ↑ Heinbockel, Thomas; Csoka, Antonei B. (2019-10-23). Introductory Chapter: The Chemical Basis of Neural Function and Dysfunction. IntechOpen. ISBN   978-1-83880-000-0.
  15. ↑ Beyene, Abraham G.; Yang, Sarah J.; Landry, Markita P. (2019-07-01). "Review Article: Tools and trends for probing brain neurochemistry". Journal of Vacuum Science & Technology A. 37 (4): 040802. Bibcode:2019JVSTA..37d0802B. doi:10.1116/1.5051047. ISSN   0734-2101. PMC   6559927 . PMID   31235991.
  16. ↑ Arnsten, Amy F.T.; Raskind, Murray A.; Taylor, Fletcher B.; Connor, Daniel F. (January 2015). "The effects of stress exposure on prefrontal cortex: Translating basic research into successful treatments for post-traumatic stress disorder". Neurobiology of Stress. 1: 89–99. doi:10.1016/j.ynstr.2014.10.002. ISSN   2352-2895. PMC   4244027 . PMID   25436222.
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