Synaptopathy: Difference between revisions
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| caption = A common cause of synaptopathy is glutamate excitotoxicity. As shown in the animation, the over-activation of NMDA receptors leads to an increase in free intracellular calcium, which produces oxygen free-radicals and eventually neuronal dysfunction.<ref> |
| caption = A common cause of synaptopathy is glutamate excitotoxicity. As shown in the animation, the over-activation of NMDA receptors leads to an increase in free intracellular calcium, which produces oxygen free-radicals and eventually neuronal dysfunction.<ref>{{cite journal |last1= Mark |first1= Leighton P |last2= Prost |first2= Robert W |last3= Ulmer |first3= John L |last4= Smith |first4= Michelle M |last5= Daniels |first5= David L |last6= Strottmann |first6= James M |last7= Brown |first7=W Douglas |last8= Hacein-Bey |first8= Lotfi |date=November 2001 |title=Pictorial Review of glutamate excitotoxicity: fundamental concepts for neuroimaging |url=http://www.ajnr.org/content/22/10/1813 |journal=American Journal of Neuroradiology |volume=22 |issue=10 |pages=1813–1824 |pmid=11733308}}</ref> |
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A '''synaptopathy''' is a disease of the [[brain]], [[spinal cord]] or [[peripheral nervous system]] relating to the dysfunction of [[synapses]]. This can arise as a result of a mutation in a gene encoding a synaptic protein such as an [[ion channel]], [[neurotransmitter receptor]], or a protein involved in [[neurotransmitter release]]. It can also arise as a result of an [[autoantibody]] targeting a synaptic protein. Synaptopathies caused by [[ion channel]] mutations are also known as synaptic [[channelopathies]]. An example is [[episodic ataxia]]. [[Myasthenia gravis]] is an example of an [[autoimmune]] synaptopathy. Some toxins also affect synaptic function. Tetanus toxin and botulinum toxin affect neurotransmitter release. Tetanus toxin can enter the body via a wound, and botulinum toxin can be ingested or administered therapeutically to alleviate dystonia or as cosmetic treatment. |
A '''synaptopathy''' is a disease of the [[brain]], [[spinal cord]] or [[peripheral nervous system]] relating to the dysfunction of [[synapses]]. This can arise as a result of a mutation in a gene encoding a synaptic protein such as an [[ion channel]], [[neurotransmitter receptor]], or a protein involved in [[neurotransmitter release]]. It can also arise as a result of an [[autoantibody]] targeting a synaptic protein. Synaptopathies caused by [[ion channel]] mutations are also known as synaptic [[channelopathies]]. An example is [[episodic ataxia]]. [[Myasthenia gravis]] is an example of an [[autoimmune]] synaptopathy. Some toxins also affect synaptic function. Tetanus toxin and botulinum toxin affect neurotransmitter release. Tetanus toxin can enter the body via a wound, and botulinum toxin can be ingested or administered therapeutically to alleviate dystonia or as cosmetic treatment. |
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Another example of synaptopathy occurs in the auditory system. This cochlear synaptopathy has been seen after prolonged noise exposure in both primate and non-primate models. <ref> |
Another example of synaptopathy occurs in the auditory system. This cochlear synaptopathy has been seen after prolonged noise exposure in both primate and non-primate models. <ref>{{cite journal |last1= Valero |first1= MD |last2= Burton |first2= JA |last3= Hauser |first3= SN |last4= Hackett |first4= TA |last5= Ramachandran |first5= R |last6= Liberman |first6=MC |date=September 2017 |title=Noise-induced cochlear synaptopathy in rhesus monkeys (Macaca mulatta) |url=http://www.sciencedirect.com/science/article/pii/S0378595517301168 |journal=Hearing Research |volume=353 |pages= 213–223 |doi=10.1016/j.heares.2017.07.003 |pmid= 28712672}}</ref><ref>{{cite journal |last1= Ruel |first1= Jérôme |last2= Wang |first2= Jing |last3= Rebillard |first3= Guy |last4= Eybalin |first4= Michel |last5= Lloyd |first5= Ruth |last6= Pujol |first6= Rémy |last7= Puel |first7= Jean-Luc |date=May 2007 |title=Physiology, pharmacology and plasticity at the inner hair cell synaptic complex |url=http://www.sciencedirect.com/science/article/pii/S0378595506002474 |journal=Hearing Research |volume=227 |issue=1–2 |pages=19–27 |doi=10.1016/j.heares.2006.08.017 |pmid=17079104}}</ref> Two possible reasons for this neuronal death are both glutamate-mediated [[excitotoxicity]] in the postsynaptic terminal, and presynaptic ribbon damage which occurs by an unknown mechanism. <ref>{{cite journal |last= Pujol |first= Rémy |last2= Puel |first2= Jean‐Luc |date=November 1999|title=Excitotoxicity, synaptic repair, and functional recovery in the mammalian cochlea: a review of recent findings |url=http://onlinelibrary.wiley.com/doi/10.1111/j.1749-6632.1999.tb08646.x/abstract |journal=Annals of the New York Academy of Sciences |volume=884 |issue=1 |pages= 249–254 |doi=10.1111/j.1749-6632.1999.tb08646.x |pmid=10842598}}</ref> |
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Synaptopathies are attracting research interest because they provide an insight into fundamental mechanisms of [[synaptic transmission]] and because an improved understanding of disease mechanisms may lead to new treatments. |
Synaptopathies are attracting research interest because they provide an insight into fundamental mechanisms of [[synaptic transmission]] and because an improved understanding of disease mechanisms may lead to new treatments. |
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Some diseases of unknown etiology have been proposed to be synaptopathies. Examples include [[autism spectrum disorder]] and [[schizophrenia]]. Synaptic dysfunction can also occur in [[neurodegenerative]] disorders such as [[Alzheimer's disease|Alzheimer's]]. Increasing knowledge of the genetic basis of these diseases has linked proteins to the function of the synapse. Age-related cochlear synaptic and neural degeneration has also been demonstrated in mice.<ref>{{cite |
Some diseases of unknown etiology have been proposed to be synaptopathies. Examples include [[autism spectrum disorder]] and [[schizophrenia]]. Synaptic dysfunction can also occur in [[neurodegenerative]] disorders such as [[Alzheimer's disease|Alzheimer's]]. Increasing knowledge of the genetic basis of these diseases has linked proteins to the function of the synapse. Age-related cochlear synaptic and neural degeneration has also been demonstrated in mice.<ref>{{cite journal |last1=Sergeyenko |first1=Yevgeniya |last2=Lall |first2= Kumud |last3= Liberman |first3= M Charles |last4=Kujawa |first4=Sharon G |date=21 August 2013 |title=Age-related cochlear synaptopathy: an early-onset contributor to auditory functional decline |url=http://www.jneurosci.org/content/33/34/13686.full |accessdate=1 April 2015 |journal=The Journal of Neuroscience |volume=33 |issue=34 |pages=13686–13694 |doi=10.1523/JNEUROSCI.1783-13.2013 |pmc=3755715 |pmid=23966690}}</ref> |
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Molecules such as [[FMR1|FMRP1]] act as translational repressor thus when ablated such as in [[fragile X syndrome|FXS]] result in varying degrees of cellular and behavioural abnormalities. Additional molecules thought to be involved include SynGAP and [[SHANK1]].<ref>{{cite journal|last1=Brose|title=Synaptopathy: dysfunction of synaptic function?|journal= |
Molecules such as [[FMR1|FMRP1]] act as translational repressor thus when ablated such as in [[fragile X syndrome|FXS]] result in varying degrees of cellular and behavioural abnormalities. Additional molecules thought to be involved include SynGAP and [[SHANK1]].<ref>{{cite journal |last1=Brose |first1=Nils |last2=O'Connor |first2=Vincent |last3=Skehel |first3=Paul |date=April 2010 |title=Synaptopathy: dysfunction of synaptic function? |journal=Biochemical Society Transactions |volume=38 |issue=2 |page=443 |doi=10.1042/bst0380443 |pmid=20298199}}</ref> |
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==References== |
==References== |
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Revision as of 20:46, 3 October 2018
 | This article needs additional citations for verification. (November 2012) |
| Synaptopathy | |
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| A common cause of synaptopathy is glutamate excitotoxicity. As shown in the animation, the over-activation of NMDA receptors leads to an increase in free intracellular calcium, which produces oxygen free-radicals and eventually neuronal dysfunction.[1] |
A synaptopathy is a disease of the brain, spinal cord or peripheral nervous system relating to the dysfunction of synapses. This can arise as a result of a mutation in a gene encoding a synaptic protein such as an ion channel, neurotransmitter receptor, or a protein involved in neurotransmitter release. It can also arise as a result of an autoantibody targeting a synaptic protein. Synaptopathies caused by ion channel mutations are also known as synaptic channelopathies. An example is episodic ataxia. Myasthenia gravis is an example of an autoimmune synaptopathy. Some toxins also affect synaptic function. Tetanus toxin and botulinum toxin affect neurotransmitter release. Tetanus toxin can enter the body via a wound, and botulinum toxin can be ingested or administered therapeutically to alleviate dystonia or as cosmetic treatment.
Another example of synaptopathy occurs in the auditory system. This cochlear synaptopathy has been seen after prolonged noise exposure in both primate and non-primate models. [2][3] Two possible reasons for this neuronal death are both glutamate-mediated excitotoxicity in the postsynaptic terminal, and presynaptic ribbon damage which occurs by an unknown mechanism. [4]
Synaptopathies are attracting research interest because they provide an insight into fundamental mechanisms of synaptic transmission and because an improved understanding of disease mechanisms may lead to new treatments.
Some diseases of unknown etiology have been proposed to be synaptopathies. Examples include autism spectrum disorder and schizophrenia. Synaptic dysfunction can also occur in neurodegenerative disorders such as Alzheimer's. Increasing knowledge of the genetic basis of these diseases has linked proteins to the function of the synapse. Age-related cochlear synaptic and neural degeneration has also been demonstrated in mice.[5]
Molecules such as FMRP1 act as translational repressor thus when ablated such as in FXS result in varying degrees of cellular and behavioural abnormalities. Additional molecules thought to be involved include SynGAP and SHANK1.[6]
References
- ^ Mark, Leighton P; Prost, Robert W; Ulmer, John L; Smith, Michelle M; Daniels, David L; Strottmann, James M; Brown, W Douglas; Hacein-Bey, Lotfi (November 2001). "Pictorial Review of glutamate excitotoxicity: fundamental concepts for neuroimaging". American Journal of Neuroradiology. 22 (10): 1813–1824. PMID 11733308.
- ^ Valero, MD; Burton, JA; Hauser, SN; Hackett, TA; Ramachandran, R; Liberman, MC (September 2017). "Noise-induced cochlear synaptopathy in rhesus monkeys (Macaca mulatta)". Hearing Research. 353: 213–223. doi:10.1016/j.heares.2017.07.003. PMID 28712672.
- ^ Ruel, Jérôme; Wang, Jing; Rebillard, Guy; Eybalin, Michel; Lloyd, Ruth; Pujol, Rémy; Puel, Jean-Luc (May 2007). "Physiology, pharmacology and plasticity at the inner hair cell synaptic complex". Hearing Research. 227 (1–2): 19–27. doi:10.1016/j.heares.2006.08.017. PMID 17079104.
- ^ Pujol, Rémy; Puel, Jean‐Luc (November 1999). "Excitotoxicity, synaptic repair, and functional recovery in the mammalian cochlea: a review of recent findings". Annals of the New York Academy of Sciences. 884 (1): 249–254. doi:10.1111/j.1749-6632.1999.tb08646.x. PMID 10842598.
- ^ Sergeyenko, Yevgeniya; Lall, Kumud; Liberman, M Charles; Kujawa, Sharon G (21 August 2013). "Age-related cochlear synaptopathy: an early-onset contributor to auditory functional decline". The Journal of Neuroscience. 33 (34): 13686–13694. doi:10.1523/JNEUROSCI.1783-13.2013. PMC 3755715. PMID 23966690. Retrieved 1 April 2015.
- ^ Brose, Nils; O'Connor, Vincent; Skehel, Paul (April 2010). "Synaptopathy: dysfunction of synaptic function?". Biochemical Society Transactions. 38 (2): 443. doi:10.1042/bst0380443. PMID 20298199.