Synaptopathy
 | This articleneeds additional citations forverification.(November 2012) |
| Synaptopathy | |
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| A common cause of synaptopathy is glutamateexcitotoxicity.As shown in the animation, the over-activation ofNMDA receptorsleads to an increase in free intracellular calcium, which produces oxygen free-radicals and eventually neuronal dysfunction.[1] |
Asynaptopathyis a disease of thebrain,spinal cordorperipheral nervous systemrelating to the dysfunction ofsynapses.This can arise as a result of a mutation in a gene encoding a synaptic protein such as anion channel,neurotransmitter receptor,or a protein involved inneurotransmitter release.It can also arise as a result of anautoantibodytargeting a synaptic protein. Synaptopathies caused byion channelmutations are also known as synapticchannelopathies.An example isepisodic ataxia.Myasthenia gravisis an example of anautoimmunesynaptopathy. Some toxins also affect synaptic function.Tetanus toxinandbotulinum toxinaffect neurotransmitter release. Tetanus toxin can enter the body via a wound, and botulinum toxin can be ingested or administered therapeutically to alleviatedystoniaor 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-mediatedexcitotoxicityin 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 ofsynaptic transmissionand because an improved understanding of disease mechanisms may lead to new treatments.
Some diseases of unknown etiology have been proposed to be synaptopathies. Examples includeautism spectrum disorder[5]andschizophrenia.[6]Synaptic dysfunction can also occur inneurodegenerativedisorders such asAlzheimer's.[7]Immune-mediated cerebellar ataxias represent a group of disorders causing cerebellar ataxia induced by a dysfunction of synapses.[8]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.[9]
Molecules such asFMRP1act as translational repressor thus when ablated such as inFXSresult in varying degrees of cellular and behavioural abnormalities. Additional molecules thought to be involved include SynGAP andSHANK1.[10]
References
[edit]- ^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.PMC7973850.PMID11733308.
- ^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.PMC5632522.PMID28712672.
- ^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.PMID17079104.S2CID21778893.
- ^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.Bibcode:1999NYASA.884..249P.doi:10.1111/j.1749-6632.1999.tb08646.x.PMID10842598.S2CID25371542.
- ^Wang, Xin xing; Kery, Rachel; Xiong, Qiaojie (June 2018). "Synaptopathology in autism spectrum disorders: Complex effects of synaptic genes on neural circuits".Progress in Neuro-Psychopharmacology and Biological Psychiatry.84(Pt B): 398–415.doi:10.1016/j.pnpbp.2017.09.026.ISSN0278-5846.PMID28986278.S2CID207411792.
- ^Hayashi-Takagi, Akiko (January 2017)."Synapse pathology and translational applications for schizophrenia".Neuroscience Research.114:3–8.doi:10.1016/j.neures.2016.09.001.PMID27633835.S2CID1806948.
- ^Jha, Saurabh Kumar; Jha, Niraj Kumar; Kumar, Dhiraj; Sharma, Renu; Shrivastava, Abhishek; Ambasta, Rashmi K.; Kumar, Pravir (2017). "Stress-induced synaptic dysfunction and neurotransmitter release in Alzheimer's Disease: Can neurotransmitters and neuromodulators be potential therapeutic targets?".Journal of Alzheimer's Disease.57(4): 1017–1039.doi:10.3233/JAD-160623.PMID27662312.
- ^Mitoma, H.; Honnorat, J.; Yamaguchi, K.; Manto, M. (2020)."Fundamental Mechanisms of Autoantibody-Induced Impairments on Ion Channels and Synapses in Immune-Mediated Cerebellar Ataxias".Int J Mol Sci.21(14): E4936.doi:10.3390/ijms21144936.PMC7404345.PMID32668612.
- ^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.PMC3755715.PMID23966690.
- ^Brose, Nils; O'Connor, Vincent; Skehel, Paul (April 2010). "Synaptopathy: dysfunction of synaptic function?".Biochemical Society Transactions.38(2): 443–4.doi:10.1042/bst0380443.PMID20298199.