The Role of Zinc and NMDA Receptors in Autism Spectrum Disorders
NMDA-type glutamate receptors are critical for synaptic plasticity in the central nervous system. Their unique properties and age-dependent arrangement of subunit types underpin their role as a coincidence detector of pre- and postsynaptic activity during brain development and maturation. NMDAR func...
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| Format: | Article |
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MDPI AG
2022-12-01
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| Series: | Pharmaceuticals |
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| Online Access: | https://www.mdpi.com/1424-8247/16/1/1 |
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| author | Kevin Lee Zoe Mills Pangying Cheung Juliette E. Cheyne Johanna M. Montgomery |
| author_facet | Kevin Lee Zoe Mills Pangying Cheung Juliette E. Cheyne Johanna M. Montgomery |
| author_sort | Kevin Lee |
| collection | DOAJ |
| description | NMDA-type glutamate receptors are critical for synaptic plasticity in the central nervous system. Their unique properties and age-dependent arrangement of subunit types underpin their role as a coincidence detector of pre- and postsynaptic activity during brain development and maturation. NMDAR function is highly modulated by zinc, which is co-released with glutamate and concentrates in postsynaptic spines. Both NMDARs and zinc have been strongly linked to autism spectrum disorders (ASDs), suggesting that NMDARs are an important player in the beneficial effects observed with zinc in both animal models and children with ASDs. Significant evidence is emerging that these beneficial effects occur via zinc-dependent regulation of SHANK proteins, which form the backbone of the postsynaptic density. For example, dietary zinc supplementation enhances SHANK2 or SHANK3 synaptic recruitment and rescues NMDAR deficits and hypofunction in <i>Shank3<sup>ex13–16−/−</sup></i> and <i>Tbr1<sup>+/−</sup></i> ASD mice. Across multiple studies, synaptic changes occur in parallel with a reversal of ASD-associated behaviours, highlighting the zinc-dependent regulation of NMDARs and glutamatergic synapses as therapeutic targets for severe forms of ASDs, either pre- or postnatally. The data from rodent models set a strong foundation for future translational studies in human cells and people affected by ASDs. |
| first_indexed | 2024-04-10T21:13:08Z |
| format | Article |
| id | doaj.art-6595332e65594475b3ccdefec7a2c8af |
| institution | Directory Open Access Journal |
| issn | 1424-8247 |
| language | English |
| last_indexed | 2024-04-10T21:13:08Z |
| publishDate | 2022-12-01 |
| publisher | MDPI AG |
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| series | Pharmaceuticals |
| spelling | doaj.art-6595332e65594475b3ccdefec7a2c8af2023-01-20T15:26:33ZengMDPI AGPharmaceuticals1424-82472022-12-01161110.3390/ph16010001The Role of Zinc and NMDA Receptors in Autism Spectrum DisordersKevin Lee0Zoe Mills1Pangying Cheung2Juliette E. Cheyne3Johanna M. Montgomery4Department of Physiology and Centre for Brain Research, University of Auckland, Auckland 1010, New ZealandDepartment of Physiology and Centre for Brain Research, University of Auckland, Auckland 1010, New ZealandDepartment of Physiology and Centre for Brain Research, University of Auckland, Auckland 1010, New ZealandDepartment of Physiology and Centre for Brain Research, University of Auckland, Auckland 1010, New ZealandDepartment of Physiology and Centre for Brain Research, University of Auckland, Auckland 1010, New ZealandNMDA-type glutamate receptors are critical for synaptic plasticity in the central nervous system. Their unique properties and age-dependent arrangement of subunit types underpin their role as a coincidence detector of pre- and postsynaptic activity during brain development and maturation. NMDAR function is highly modulated by zinc, which is co-released with glutamate and concentrates in postsynaptic spines. Both NMDARs and zinc have been strongly linked to autism spectrum disorders (ASDs), suggesting that NMDARs are an important player in the beneficial effects observed with zinc in both animal models and children with ASDs. Significant evidence is emerging that these beneficial effects occur via zinc-dependent regulation of SHANK proteins, which form the backbone of the postsynaptic density. For example, dietary zinc supplementation enhances SHANK2 or SHANK3 synaptic recruitment and rescues NMDAR deficits and hypofunction in <i>Shank3<sup>ex13–16−/−</sup></i> and <i>Tbr1<sup>+/−</sup></i> ASD mice. Across multiple studies, synaptic changes occur in parallel with a reversal of ASD-associated behaviours, highlighting the zinc-dependent regulation of NMDARs and glutamatergic synapses as therapeutic targets for severe forms of ASDs, either pre- or postnatally. The data from rodent models set a strong foundation for future translational studies in human cells and people affected by ASDs.https://www.mdpi.com/1424-8247/16/1/1NMDA receptorsynaptic plasticityautism spectrum disorderglutamatezinc |
| spellingShingle | Kevin Lee Zoe Mills Pangying Cheung Juliette E. Cheyne Johanna M. Montgomery The Role of Zinc and NMDA Receptors in Autism Spectrum Disorders Pharmaceuticals NMDA receptor synaptic plasticity autism spectrum disorder glutamate zinc |
| title | The Role of Zinc and NMDA Receptors in Autism Spectrum Disorders |
| title_full | The Role of Zinc and NMDA Receptors in Autism Spectrum Disorders |
| title_fullStr | The Role of Zinc and NMDA Receptors in Autism Spectrum Disorders |
| title_full_unstemmed | The Role of Zinc and NMDA Receptors in Autism Spectrum Disorders |
| title_short | The Role of Zinc and NMDA Receptors in Autism Spectrum Disorders |
| title_sort | role of zinc and nmda receptors in autism spectrum disorders |
| topic | NMDA receptor synaptic plasticity autism spectrum disorder glutamate zinc |
| url | https://www.mdpi.com/1424-8247/16/1/1 |
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