Abstract
Autism spectrum disorder (ASD) is a complicated, interpersonally defined, static condition of the underdeveloped brain. Although the aetiology of autism remains unclear, disturbance of neuronglia interactions has lately been proposed as a significant event in the pathophysiology of ASD. In recent years, the contribution of glial cells to autism has been overlooked. In addition to neurons, glial cells play an essential role in mental activities, and a new strategy that emphasises neuron-glia interactions should be applied. Disturbance of neuron-glia connections has lately been proposed as a significant event in the pathophysiology of ASD because aberrant neuronal network formation and dysfunctional neurotransmission are fundamental to the pathology of the condition. In ASD, neuron and glial cell number changes cause brain circuits to malfunction and impact behaviour. A study revealed that reactive glial cells result in the loss of synaptic functioning and induce autism under inflammatory conditions. Recent discoveries also suggest that dysfunction or changes in the ability of microglia to carry out physiological and defensive functions (such as failure in synaptic elimination or aberrant microglial activation) may be crucial for developing brain diseases, especially autism. The cerebellum, white matter, and cortical regions of autistic patients showed significant microglial activation. Reactive glial cells result in the loss of synaptic functioning and induce autism under inflammatory conditions. Replacement of defective glial cells (Cell-replacement treatment), glial progenitor cell-based therapy, and medication therapy (inhibition of microglia activation) are all utilised to treat glial dysfunction. This review discusses the role of glial cells in ASD and the various potential approaches to treating glial cell dysfunction.
Graphical Abstract
[http://dx.doi.org/10.1016/bs.pmbts.2020.04.011] [PMID: 32711814]
[http://dx.doi.org/10.3389/fpsyt.2013.00139] [PMID: 24155727]
[http://dx.doi.org/10.1038/nrn1928] [PMID: 16715052]
[http://dx.doi.org/10.1016/j.conb.2016.09.016] [PMID: 27788368]
[http://dx.doi.org/10.1590/S0100-879X2001000500008] [PMID: 11323747]
[http://dx.doi.org/10.1016/j.neuron.2020.11.007] [PMID: 33271068]
[http://dx.doi.org/10.1016/j.neuroscience.2018.04.046] [PMID: 29753862]
[http://dx.doi.org/10.1002/glia.22727] [PMID: 25132502]
[http://dx.doi.org/10.1038/nn.3531] [PMID: 24077561]
[http://dx.doi.org/10.1155/2016/5214961] [PMID: 26881114]
[http://dx.doi.org/10.3389/fcell.2021.653101] [PMID: 33763430]
[http://dx.doi.org/10.1017/S1740925X0800001X] [PMID: 18634563]
[http://dx.doi.org/10.1007/s11064-017-2387-5] [PMID: 28918515]
[http://dx.doi.org/10.3389/fncel.2020.00020] [PMID: 32116564]
[http://dx.doi.org/10.3233/JAD-2009-0988] [PMID: 19276541]
[http://dx.doi.org/10.1038/s41598-019-45348-z] [PMID: 31217543]
[http://dx.doi.org/10.1016/S0149-7634(99)00080-9] [PMID: 10781693]
[http://dx.doi.org/10.1146/annurev-pathol-012414-040405] [PMID: 25621659]
[http://dx.doi.org/10.4065/80.10.1326] [PMID: 16212146]
[http://dx.doi.org/10.1038/nature11310] [PMID: 22763451]
[http://dx.doi.org/10.1016/j.neuron.2014.06.033] [PMID: 25088363]
[http://dx.doi.org/10.1016/j.celrep.2015.09.011] [PMID: 26456829]
[http://dx.doi.org/10.1038/nature09582] [PMID: 21068835]
[http://dx.doi.org/10.1016/j.conb.2014.03.005] [PMID: 24694749]
[http://dx.doi.org/10.1038/s41398-019-0588-1] [PMID: 31594918]
[http://dx.doi.org/10.1016/j.bbi.2017.05.015] [PMID: 28546058]
[http://dx.doi.org/10.1186/2040-2392-2-13] [PMID: 21810230]
[http://dx.doi.org/10.1016/j.cell.2013.11.024] [PMID: 24315484]
[http://dx.doi.org/10.1126/science.aad0314] [PMID: 26822608]
[http://dx.doi.org/10.1001/archpedi.159.2.151] [PMID: 15699309]
[http://dx.doi.org/10.1523/JNEUROSCI.1895-18.2019] [PMID: 30683682]
[http://dx.doi.org/10.1111/ejn.14838] [PMID: 32463535]
[http://dx.doi.org/10.1542/peds.113.5.e472] [PMID: 15121991]
[http://dx.doi.org/10.3390/cells9102176] [PMID: 32992620]
[http://dx.doi.org/10.3389/fncel.2016.00021] [PMID: 26903806]
[http://dx.doi.org/10.1016/j.biopsych.2008.05.014] [PMID: 18602089]
[http://dx.doi.org/10.1080/02646830500381930] [PMID: 16401547]
[http://dx.doi.org/10.1159/000398791] [PMID: 25998072]
[http://dx.doi.org/10.1186/s13229-018-0254-0] [PMID: 30603062]
[http://dx.doi.org/10.1002/ana.20315] [PMID: 15546155]
[http://dx.doi.org/10.1016/j.tins.2019.05.011] [PMID: 31300246]
[http://dx.doi.org/10.1016/j.biopsych.2015.03.012] [PMID: 25861701]
[http://dx.doi.org/10.1038/nature10110] [PMID: 21614001]
[http://dx.doi.org/10.1186/2040-2392-5-3] [PMID: 24410870]
[http://dx.doi.org/10.1016/j.gpb.2016.04.003] [PMID: 27245308]
[http://dx.doi.org/10.1177/13623613211014408] [PMID: 34107793]
[http://dx.doi.org/10.1016/j.expneurol.2016.05.010]
[http://dx.doi.org/10.1523/JNEUROSCI.1781-07.2007] [PMID: 17670977]
[http://dx.doi.org/10.3389/fncel.2020.00278] [PMID: 32973460]
[http://dx.doi.org/10.1017/S1740925X12000142] [PMID: 22874006]
[http://dx.doi.org/10.1016/j.neubiorev.2013.11.008] [PMID: 24300694]
[http://dx.doi.org/10.1038/s41467-020-15530-3] [PMID: 32286273]
[http://dx.doi.org/10.1101/gad.188326.112] [PMID: 22549954]
[http://dx.doi.org/10.1038/s41467-021-23843-0] [PMID: 34059669]
[http://dx.doi.org/10.1016/j.biopsych.2017.09.021] [PMID: 29129319]
[http://dx.doi.org/10.2174/1570159X11311020004] [PMID: 23997752]
[http://dx.doi.org/10.1017/S1092852919001603] [PMID: 31659946]
[http://dx.doi.org/10.1186/scrt128] [PMID: 23021042]
[http://dx.doi.org/10.1371/journal.pone.0017328] [PMID: 21407803]
[http://dx.doi.org/10.1016/j.neulet.2013.10.055] [PMID: 24184876]
[http://dx.doi.org/10.1016/bs.pbr.2017.02.010] [PMID: 28554396]
[http://dx.doi.org/10.1523/JNEUROSCI.19-22-09986.1999] [PMID: 10559406]
[http://dx.doi.org/10.1126/science.1218071] [PMID: 23112326]
[http://dx.doi.org/10.1016/j.semcdb.2020.12.004] [PMID: 33414060]
[http://dx.doi.org/10.1017/S1740925X09990317] [PMID: 19807941]
[http://dx.doi.org/10.1016/j.nec.2006.10.009] [PMID: 17244557]
[http://dx.doi.org/10.1177/1073858411403317] [PMID: 21609943]
[http://dx.doi.org/10.1038/srep19003] [PMID: 26750620]
[http://dx.doi.org/10.3390/cells9112451] [PMID: 33182669]
[http://dx.doi.org/10.1016/j.celrep.2016.07.035] [PMID: 27498872]
[http://dx.doi.org/10.1212/WNL.0b013e3182a4a577] [PMID: 23946308]
[http://dx.doi.org/10.3389/fncel.2018.00488] [PMID: 30618635]
[http://dx.doi.org/10.3390/ph10040095] [PMID: 29232822]
[http://dx.doi.org/10.1517/17425255.4.10.1265] [PMID: 18798697]
[http://dx.doi.org/10.1146/annurev-immunol-032713-120240] [PMID: 24471431]
[http://dx.doi.org/10.3389/fncel.2013.00071] [PMID: 23734099]
[http://dx.doi.org/10.1159/000494761] [PMID: 30517945]
[http://dx.doi.org/10.3390/ijms21093293] [PMID: 32384730]
[http://dx.doi.org/10.3389/fncel.2020.00198] [PMID: 32848611]
[http://dx.doi.org/10.3389/fnagi.2020.594571] [PMID: 33192490]
[http://dx.doi.org/10.1186/s12974-019-1464-x] [PMID: 30961627]
[http://dx.doi.org/10.3389/fimmu.2021.676255] [PMID: 34113350]
[http://dx.doi.org/10.1186/s13229-021-00428-8] [PMID: 33676530]
[http://dx.doi.org/10.1186/s12974-021-02204-0] [PMID: 34238328]
[http://dx.doi.org/10.20517/2347-8659.2020.02] [PMID: 33154976]
[http://dx.doi.org/10.2353/ajpath.2007.070231] [PMID: 17717149]
[http://dx.doi.org/10.1016/j.neuint.2005.04.018] [PMID: 15904993]
[http://dx.doi.org/10.1371/journal.pone.0057827]
[http://dx.doi.org/10.1186/1742-2094-5-15] [PMID: 18477398]
[http://dx.doi.org/10.1159/000492225] [PMID: 30184549]
[http://dx.doi.org/10.3389/fendo.2016.00078] [PMID: 27445981]
[http://dx.doi.org/10.1155/2017/5071786]
[http://dx.doi.org/10.1186/s13063-020-04365-4] [PMID: 32513294]
[http://dx.doi.org/10.3945/jn.110.123273] [PMID: 20685893]
[http://dx.doi.org/10.1186/1742-2094-7-3] [PMID: 20074346]
[http://dx.doi.org/10.9758/cpn.2018.16.3.246] [PMID: 30121973]
[http://dx.doi.org/10.1016/j.jpain.2003.09.006] [PMID: 14975378]
[http://dx.doi.org/10.1007/s12264-022-00986-8] [PMID: 36445556]
[http://dx.doi.org/10.1016/bs.pmbts.2019.06.012] [PMID: 31601405]
[http://dx.doi.org/10.1016/j.neuroscience.2013.02.041] [PMID: 23485816]
[http://dx.doi.org/10.1186/s13287-018-0890-5] [PMID: 29871694]
[http://dx.doi.org/10.1126/science.285.5428.754] [PMID: 10427001]
[http://dx.doi.org/10.1002/glia.22859] [PMID: 26010717]
[http://dx.doi.org/10.1038/s41598-020-66753-9] [PMID: 32555386]
[http://dx.doi.org/10.1124/mol.111.071290] [PMID: 21350020]
[http://dx.doi.org/10.1111/bph.12615] [PMID: 24641282]
[http://dx.doi.org/10.1038/tp.2017.80] [PMID: 28485733]
[http://dx.doi.org/10.1016/j.brainres.2015.10.052] [PMID: 26551768]
[http://dx.doi.org/10.1038/tp.2015.142] [PMID: 26418275]
[http://dx.doi.org/10.1177/039463201202500201] [PMID: 22697063]
[http://dx.doi.org/10.1016/j.jneuroim.2009.08.012] [PMID: 19766327]
[http://dx.doi.org/10.1038/tp.2014.33] [PMID: 24937094]
[http://dx.doi.org/10.1002/acn3.424] [PMID: 28695149]
[http://dx.doi.org/10.1038/sj.npp.1300130] [PMID: 12700706]
[http://dx.doi.org/10.1186/1742-2094-7-90] [PMID: 21138577]
[http://dx.doi.org/10.1007/s00213-012-2796-8] [PMID: 22782459]
[http://dx.doi.org/10.1186/1742-2094-10-45] [PMID: 23561827]
[http://dx.doi.org/10.1371/journal.pone.0039897] [PMID: 22768159]
[http://dx.doi.org/10.1016/j.mehy.2006.10.015] [PMID: 17150311]