|
|
| (4 intermediate revisions by the same user not shown) |
| Line 1: |
Line 1: |
| {{More footnotes|date=August 2014}} | | {{Short description|Adverse effects of substances on the nervous system}} |
| | '''Neurotoxicity''' refers to the damage to the [[nervous system]] caused by exposure to natural or artificial toxic substances, known as [[neurotoxins]]. These substances can adversely affect the function of [[neurons]], which are the primary cells of the nervous system responsible for transmitting and processing information. |
|
| |
|
| '''Neurotoxicity''' is a form of [[toxicity]] in which a biological, chemical, or physical agent produces an adverse effect on the structure or function of the [[central nervous system|central]] and/or [[peripheral nervous system|peripheral]] [[nervous system]].<ref name="Neurotoxicity review">{{cite journal | vauthors = Cunha-Oliveira T, Rego AC, Oliveira CR | title = Cellular and molecular mechanisms involved in the neurotoxicity of opioid and psychostimulant drugs | journal = Brain Research Reviews | volume = 58 | issue = 1 | pages = 192–208 | date = June 2008 | pmid = 18440072 | doi = 10.1016/j.brainresrev.2008.03.002 | quote = The Interagency Committee on Neurotoxicology defined neurotoxicity as a broad concept, including any adverse effect on the structure or function of the central and/or peripheral nervous system by a biological, chemical or physical agent. In this definition, neurotoxic effects may be permanent or reversible and result from direct or indirect actions on the nervous system (Erinoff, 1995).| hdl = 10316/4676 | url = https://estudogeral.sib.uc.pt/bitstream/10316/4676/1/file0b55e04b59fa488cb610af0d72a5683b.pdf }}</ref> It occurs when exposure to a substance – specifically, a [[neurotoxin]] or [[neurotoxicant]]– alters the normal activity of the nervous system in such a way as to cause permanent or reversible damage to [[nervous tissue]].<ref name="Neurotoxicity review" /> This can eventually disrupt or even kill [[neuron]]s, which are cells that [[neurotransmission|transmit and process signals]] in the brain and other parts of the nervous system. Neurotoxicity can result from [[organ transplant]]s, [[radiation treatment]], certain [[drug therapy|drug therapies]] (e.g., substances used in [[chemotherapy]]), [[recreational drug use]], and exposure to [[heavy metals]], bites from certain species of [[venomous snake]]s, [[pesticide]]s,<ref>Neurotoxicity of pesticides. Keifer MC(1), Firestone J. Author information: (1)University of Washington, Department of Medicine, Seattle, WA 98195-7234, USA., 2007</ref><ref>Jan 1, 2008 - Neurotoxicity of pesticides: a brief review. Costa LG(1), Giordano G, Guizzetti M, Vitalone A. Author information: (1)Dept. of Environmental and ...</ref> certain industrial cleaning [[solvent]]s<ref>{{Cite journal|last=Sainio|first=Markku Alarik|date=2015|title=Neurotoxicity of solvents|journal=Handbook of Clinical Neurology|volume=131|pages=93–110|doi=10.1016/B978-0-444-62627-1.00007-X|issn=0072-9752|pmid=26563785|isbn=9780444626271}}</ref>, fuels<ref>{{Cite journal|last=Ritchie|first=G. D.|last2=Still|first2=K. R.|last3=Alexander|first3=W. K.|last4=Nordholm|first4=A. F.|last5=Wilson|first5=C. L.|last6=Rossi|first6=J.|last7=Mattie|first7=D. R.|date=2001-07-07|title=A review of the neurotoxicity risk of selected hydrocarbon fuels|journal=Journal of Toxicology and Environmental Health Part B: Critical Reviews|volume=4|issue=3|pages=223–312|doi=10.1080/109374001301419728|issn=1093-7404|pmid=11503417}}</ref> and certain naturally occurring substances. Symptoms may appear immediately after exposure or be delayed. They may include limb weakness or numbness, loss of memory, vision, and/or intellect, uncontrollable obsessive and/or compulsive behaviors, delusions, headache, cognitive and behavioral problems and sexual dysfunction. Chronic mold exposure in homes can lead to neurotoxicity which may not appear for months to years of exposure. All symptoms listed above are consistent with mold mycotoxin accumulation.<ref>{{Cite journal|last=Kilburn|first=Kaye H.|date=2004|title=Role of molds and mycotoxins in being sick in buildings: neurobehavioral and pulmonary impairment|journal=Advances in Applied Microbiology|volume=55|pages=339–359|doi=10.1016/S0065-2164(04)55013-X|issn=0065-2164|pmid=15350801|isbn=9780120026579}}</ref>
| | ==Mechanisms of Neurotoxicity== |
| | Neurotoxicity can occur through various mechanisms, including: |
|
| |
|
| The term ''neurotoxicity'' implies the involvement of a neurotoxin; however, the term ''neurotoxic'' may be used more loosely to describe states that are known to cause physical [[brain damage]], but where no specific neurotoxin has been identified.
| | * '''Disruption of Neuronal Communication''': Neurotoxins can interfere with the normal transmission of signals between neurons by affecting [[neurotransmitter]] release, uptake, or receptor binding. |
| | * '''Oxidative Stress''': Many neurotoxins induce oxidative stress, leading to the production of [[reactive oxygen species]] (ROS) that can damage cellular components such as [[lipids]], [[proteins]], and [[DNA]]. |
| | * '''Mitochondrial Dysfunction''': Neurotoxins can impair the function of [[mitochondria]], the energy-producing organelles in cells, leading to energy deficits and cell death. |
| | * '''Apoptosis and Necrosis''': Exposure to neurotoxins can trigger programmed cell death (apoptosis) or uncontrolled cell death (necrosis) in neurons. |
|
| |
|
| The presence of [[neurocognitive deficit]]s alone is not usually considered sufficient evidence of neurotoxicity, as many substances may impair [[neurocognitive]] performance without resulting in the death of neurons. This may be due to the direct action of the substance, with the impairment and neurocognitive deficits being temporary, and resolving when the substance is [[drug elimination|eliminated]] from the body. In some cases the level or exposure-time may be critical, with some substances only becoming neurotoxic in certain doses or time periods. Some of the most common naturally occurring brain toxins that lead to neurotoxicity as a result of excessive drug use are [[beta amyloid]] (Aβ), [[glutamate]], [[dopamine]], and [[oxygen radicals]]. When present in high concentrations, they can lead to neurotoxicity and death ([[apoptosis]]). Some of the symptoms that result from cell death include loss of motor control, cognitive deterioration and autonomic nervous system dysfunction. Additionally, neurotoxicity has been found to be a major cause of [[neurodegenerative diseases]] such as [[Alzheimer's disease]] (AD).
| | ==Common Neurotoxins== |
| | Several substances are known to be neurotoxic, including: |
|
| |
|
| ==Neurotoxic agents==
| | * '''Heavy Metals''': [[Lead]], [[mercury]], and [[arsenic]] are well-known neurotoxins that can cause significant damage to the nervous system. |
| | * '''Pesticides''': Certain [[organophosphates]] and [[carbamates]] used in agriculture can be neurotoxic. |
| | * '''Solvents''': Industrial solvents such as [[toluene]] and [[xylene]] can have neurotoxic effects. |
| | * '''Drugs and Alcohol''': Chronic use of substances like [[alcohol]], [[methamphetamine]], and [[cocaine]] can lead to neurotoxicity. |
|
| |
|
| ===Beta amyloid=== | | ==Symptoms of Neurotoxicity== |
| Aβ was found to cause neurotoxicity and cell death in the brain when present in high concentrations. Aβ results from a mutation that occurs when protein chains are cut at the wrong locations, resulting in chains of different lengths that are unusable. Thus they are left in the brain until they are broken down, but if enough accumulate, they form [[Senile plaques|plaques]] which are toxic to [[neurons]]. Aβ uses several routes in the [[central nervous system]] to cause cell death. An example is through the [[nicotinic acetylcholine receptor]] (nAchRs), which is a receptor commonly found along the surfaces of the cells that respond to nicotine stimulation, turning them on or off. Aβ was found manipulating the level of [[nicotine]] in the brain along with the [[MAP kinase]], another signaling receptor, to cause cell death. Another chemical in the brain that Aβ regulates is [[JNK]]; this chemical halts the [[extracellular signal-regulated kinases]] (ERK) pathway, which normally functions as memory control in the brain. As a result, this memory favoring pathway is stopped, and the brain loses essential memory function. The loss of memory is a symptom of [[neurodegenerative disease]], including AD. Another way Aβ causes cell death is through the phosphorylation of [[AKT]]; this occurs as the element phosphate is bound to several sites on the protein. This phosphorylation allows AKT to interact with [[Bcl-2-associated death promoter|BAD]], a protein known to cause cell death. Thus an increase in Aβ results in an increase of the AKT/BAD complex, in turn stopping the action of the anti-apoptotic protein [[Bcl-2]], which normally functions to stop cell death, causing accelerated neuron breakdown and the progression of AD.
| | The symptoms of neurotoxicity can vary widely depending on the specific neurotoxin and the extent of exposure. Common symptoms include: |
|
| |
|
| ===Glutamate===
| | * '''Cognitive Impairment''': Memory loss, difficulty concentrating, and confusion. |
| [[Glutamate]] is a chemical found in the brain that poses a toxic threat to [[neuron]]s when found in high concentrations. This concentration equilibrium is extremely delicate and is usually found in millimolar amounts extracellularly. When disturbed, an accumulation of glutamate occurs as a result of a mutation in the [[glutamate transporters]], which act like pumps to drain glutamate from the brain. This causes glutamate concentration to be several times higher in the blood than in the brain; in turn, the body must act to maintain equilibrium between the two concentrations by pumping the glutamate out of the bloodstream and into the neurons of the brain. In the event of a mutation, the glutamate transporters are unable to pump the glutamate back into the cells; thus a higher concentration accumulates at the [[glutamate receptors]]. This opens the ion channels, allowing calcium to enter the cell causing excitotoxicity. Glutamate results in cell death by turning on the [[N-methyl-D-aspartic acid]] receptors (NMDA); these receptors cause an increased release of calcium ions (Ca<sup>2+</sup>) into the cells. As a result, the increased concentration of Ca<sup>2+</sup> directly increases the stress on [[mitochondria]], resulting in excessive [[oxidative phosphorylation]] and production of [[reactive oxygen species]] (ROS) via the activation of [[nitric oxide synthase]], ultimately leading to cell death. Aβ was also found aiding this route to neurotoxicity by enhancing neuron vulnerability to glutamate.
| | * '''Motor Dysfunction''': Muscle weakness, tremors, and coordination problems. |
| | * '''Sensory Disturbances''': Numbness, tingling, and loss of sensation. |
| | * '''Behavioral Changes''': Mood swings, anxiety, and depression. |
|
| |
|
| ===Oxygen radicals=== | | ==Diagnosis and Treatment== |
| The formation of [[oxygen radicals]] in the brain is achieved through the [[nitric oxide synthase]] (NOS) pathway. This reaction occurs as a response to an increase in the Ca<sup>2+</sup> concentration inside a brain cell. This interaction between the Ca<sup>2+</sup> and NOS results in the formation of the cofactor [[tetrahydrobiopterin]] (BH4), which then moves from the plasma membrane into the cytoplasm. As a final step, NOS is dephosphorylated yielding [[nitric oxide]] (NO), which accumulates in the brain, increasing its [[oxidative stress]]. There are several ROS, including [[superoxide]], [[hydrogen peroxide]] and [[hydroxyl]], all of which lead to neurotoxicity. Naturally, the body utilizes a defensive mechanism to diminish the fatal effects of the reactive species by employing certain enzymes to break down the ROS into small, benign molecules of simple oxygen and water. However, this breakdown of the ROS is not completely efficient; some reactive residues are left in the brain to accumulate, contributing to neurotoxicity and cell death. The brain is more vulnerable to oxidative stress than other organs, due to its low oxidative capacity. Because [[neuron]]s are characterized as [[postmitotic]] cells, meaning that they live with accumulated damage over the years, accumulation of ROS is fatal. Thus, increased levels of ROS age neurons, which leads to accelerated neurodegenerative processes and ultimately the advancement of AD.
| | Diagnosing neurotoxicity involves a combination of clinical evaluation, [[neuroimaging]] techniques, and laboratory tests to identify the presence of neurotoxins. Treatment focuses on removing the source of exposure, managing symptoms, and supporting recovery through rehabilitation. |
|
| |
|
| ==Prognosis== | | ==Prevention== |
| The prognosis depends upon the length and degree of exposure and the severity of neurological injury. In some instances, exposure to neurotoxins or neurotoxicants can be fatal. In others, patients may survive but not fully recover. In other situations, many individuals recover completely after treatment.<ref>{{Cite book|title=Environmental neurotoxicology|date=1992|publisher=National Academy Press|others=National Research Council (U.S.). Committee on Neurotoxicology and Models for Assessing Risk.|isbn=0-585-14379-X|location=Washington, D.C.|oclc=44957274}}</ref>
| | Preventing neurotoxicity involves minimizing exposure to known neurotoxins through: |
|
| |
|
| The word ''neurotoxicity'' ({{IPAc-en|ˌ|n|ʊər|oʊ-|t|ɒ|k|ˈ|s|ɪ|s|ᵻ|t|i}}) uses [[classical compound|combining forms]] of ''[[wikt:neuro-#Prefix|neuro-]]'' + ''[[wikt:tox-#Prefix|tox-]]'' + ''[[wikt:-icity#Suffix|-icity]]'', yielding "[[nervous tissue]] poisoning".
| | * '''Regulation and Safety Standards''': Implementing and adhering to safety standards for the use of chemicals in industry and agriculture. |
| | | * '''Personal Protective Equipment (PPE)''': Using appropriate PPE when handling potentially neurotoxic substances. |
| ==See also==
| | * '''Public Health Initiatives''': Educating the public about the risks of neurotoxins and promoting safe practices. |
| {{col div|colwidth=30em}}
| |
| * [[Batrachotoxin]]
| |
| * [[Cytotoxicity]]
| |
| * [[Multiple chemical sensitivity]]
| |
| * [[Nephrotoxicity]]
| |
| * [[Ototoxicity]]
| |
| * [[Penitrem A]]
| |
| * [[Excitotoxicity]]
| |
| * [[Toxicity]]
| |
| {{colend}}
| |
| | |
| ==Further reading==
| |
| {{Scholia}}
| |
| *{{citation |doi=10.1007/s12031-009-9236-1 |title=Mechanisms of Neuroprotective Effects of Nicotine and Acetylcholinesterase Inhibitors: Role of α4 and α7 Receptors in Neuroprotection |year=2009 |last1=Akaike |first1=Akinori |last2=Takada-Takatori |first2=Yuki |last3=Kume |first3=Toshiaki |last4=Izumi |first4=Yasuhiko |journal=Journal of Molecular Neuroscience |volume=40 |pages=211–6 |pmid=19714494 |issue=1–2}}
| |
| *{{Citation|title=Nicotinic Acetylcholine Receptor Signaling: Roles in Alzheimer's Disease and Amyloid Neuroprotection|journal= Pharmacological Reviews |volume=61|issue=1|year=2009|pages=39–61|doi=10.1124/pr.108.000562|pmid= 19293145 |last1=Buckingham|first1=S. D.|last2=Jones|first2=A. K.|last3=Brown|first3=L. A.|last4=Sattelle|first4=D. B.|pmc=2830120}}
| |
| *{{Citation|author1=Burkle, A |author2=Huber, A |author3=Stuchbury, G |title=Neuroprotective Therapies for Alzheimer's Disease|journal= Current Pharmaceutical Design|volume= 12|issue=6|year=2006|pages=705–717|doi=10.2174/138161206775474251|pmid=16472161|display-authors=etal}}
| |
| *{{Citation|pmid=19252271|year=2009|last1=Takada-Takatori|first1=Y|last2=Kume|first2=T|last3=Izumi|first3=Y|last4=Ohgi|first4=Y|last5=Niidome|first5=T|last6=Fujii|first6=T|last7=Sugimoto|first7=H|last8=Akaike|first8=A|title=Roles of nicotinic receptors in acetylcholinesterase inhibitor-induced neuroprotection and nicotinic receptor up-regulation|volume=32|issue=3|pages=318–24|journal=Biological & Pharmaceutical Bulletin|doi=10.1248/bpb.32.318|doi-access=free}}
| |
| *{{citation|pmid=16762377|year=2006|last1=Takada-Takatori|first1=Y|last2=Kume|first2=T|last3=Sugimoto|first3=M|last4=Katsuki|first4=H|last5=Sugimoto|first5=H|last6=Akaike|first6=A|title=Acetylcholinesterase inhibitors used in treatment of Alzheimer's disease prevent glutamate neurotoxicity via nicotinic acetylcholine receptors and phosphatidylinositol 3-kinase cascade|volume=51|issue=3|pages=474–86|doi=10.1016/j.neuropharm.2006.04.007|journal=Neuropharmacology}}
| |
| *{{Citation|pmid=19252273|year=2009|last1=Shimohama|first1=S|title=Nicotinic receptor-mediated neuroprotection in neurodegenerative disease models|volume=32|issue=3|pages=332–6|journal=Biological & Pharmaceutical Bulletin|doi=10.1248/bpb.32.332|doi-access=free}}
| |
| | |
| ==References==
| |
| {{Reflist}}
| |
|
| |
|
| | ==Related Pages== |
| | * [[Neurodegenerative disease]] |
| | * [[Toxicology]] |
| | * [[Central nervous system]] |
| | * [[Peripheral nervous system]] |
| {{Neurotoxins}} | | {{Neurotoxins}} |
|
| |
| [[Category:Neurological disorders]] | | [[Category:Neurological disorders]] |
| [[Category:Toxicology]] | | [[Category:Toxicology]] |
| | [[Category:Neurotoxicity]] |
| | [[Category:Toxicology]] |
| | [[Category:Neurology]] |
Adverse effects of substances on the nervous system
Neurotoxicity refers to the damage to the nervous system caused by exposure to natural or artificial toxic substances, known as neurotoxins. These substances can adversely affect the function of neurons, which are the primary cells of the nervous system responsible for transmitting and processing information.
Mechanisms of Neurotoxicity[edit]
Neurotoxicity can occur through various mechanisms, including:
- Disruption of Neuronal Communication: Neurotoxins can interfere with the normal transmission of signals between neurons by affecting neurotransmitter release, uptake, or receptor binding.
- Oxidative Stress: Many neurotoxins induce oxidative stress, leading to the production of reactive oxygen species (ROS) that can damage cellular components such as lipids, proteins, and DNA.
- Mitochondrial Dysfunction: Neurotoxins can impair the function of mitochondria, the energy-producing organelles in cells, leading to energy deficits and cell death.
- Apoptosis and Necrosis: Exposure to neurotoxins can trigger programmed cell death (apoptosis) or uncontrolled cell death (necrosis) in neurons.
Common Neurotoxins[edit]
Several substances are known to be neurotoxic, including:
Symptoms of Neurotoxicity[edit]
The symptoms of neurotoxicity can vary widely depending on the specific neurotoxin and the extent of exposure. Common symptoms include:
- Cognitive Impairment: Memory loss, difficulty concentrating, and confusion.
- Motor Dysfunction: Muscle weakness, tremors, and coordination problems.
- Sensory Disturbances: Numbness, tingling, and loss of sensation.
- Behavioral Changes: Mood swings, anxiety, and depression.
Diagnosis and Treatment[edit]
Diagnosing neurotoxicity involves a combination of clinical evaluation, neuroimaging techniques, and laboratory tests to identify the presence of neurotoxins. Treatment focuses on removing the source of exposure, managing symptoms, and supporting recovery through rehabilitation.
Prevention[edit]
Preventing neurotoxicity involves minimizing exposure to known neurotoxins through:
- Regulation and Safety Standards: Implementing and adhering to safety standards for the use of chemicals in industry and agriculture.
- Personal Protective Equipment (PPE): Using appropriate PPE when handling potentially neurotoxic substances.
- Public Health Initiatives: Educating the public about the risks of neurotoxins and promoting safe practices.
Related Pages[edit]
