Interneuron Dysfunction and Inhibitory Deficits in Autism and Fragile X Syndrome
The alteration of excitatory–inhibitory (E–I) balance has been implicated in various neurological and psychiatric diseases, including autism spectrum disorder (ASD). Fragile X syndrome (FXS) is a single-gene disorder that is the most common known cause of ASD. Understanding the molecular and physiol...
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| Format: | Article |
| Language: | English |
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MDPI AG
2021-10-01
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| Series: | Cells |
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| Online Access: | https://www.mdpi.com/2073-4409/10/10/2610 |
| _version_ | 1797515037245440000 |
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| author | Toshihiro Nomura |
| author_facet | Toshihiro Nomura |
| author_sort | Toshihiro Nomura |
| collection | DOAJ |
| description | The alteration of excitatory–inhibitory (E–I) balance has been implicated in various neurological and psychiatric diseases, including autism spectrum disorder (ASD). Fragile X syndrome (FXS) is a single-gene disorder that is the most common known cause of ASD. Understanding the molecular and physiological features of FXS is thought to enhance our knowledge of the pathophysiology of ASD. Accumulated evidence implicates deficits in the inhibitory circuits in FXS that tips E–I balance toward excitation. Deficits in interneurons, the main source of an inhibitory neurotransmitter, gamma-aminobutyric acid (GABA), have been reported in FXS, including a reduced number of cells, reduction in intrinsic cellular excitability, or weaker synaptic connectivity. Manipulating the interneuron activity ameliorated the symptoms in the FXS mouse model, which makes it reasonable to conceptualize FXS as an interneuronopathy. While it is still poorly understood how the developmental profiles of the inhibitory circuit go awry in FXS, recent works have uncovered several developmental alterations in the functional properties of interneurons. Correcting disrupted E–I balance by potentiating the inhibitory circuit by targeting interneurons may have a therapeutic potential in FXS. I will review the recent evidence about the inhibitory alterations and interneuron dysfunction in ASD and FXS and will discuss the future directions of this field. |
| first_indexed | 2024-03-10T06:39:56Z |
| format | Article |
| id | doaj.art-d8832e49df454f98aaf846200bb4460c |
| institution | Directory Open Access Journal |
| issn | 2073-4409 |
| language | English |
| last_indexed | 2024-03-10T06:39:56Z |
| publishDate | 2021-10-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | Cells |
| spelling | doaj.art-d8832e49df454f98aaf846200bb4460c2023-11-22T17:46:21ZengMDPI AGCells2073-44092021-10-011010261010.3390/cells10102610Interneuron Dysfunction and Inhibitory Deficits in Autism and Fragile X SyndromeToshihiro Nomura0Department of Neuroscience, Feinberg School of Medicine, Northwestern University, Chicago, IL 60611, USAThe alteration of excitatory–inhibitory (E–I) balance has been implicated in various neurological and psychiatric diseases, including autism spectrum disorder (ASD). Fragile X syndrome (FXS) is a single-gene disorder that is the most common known cause of ASD. Understanding the molecular and physiological features of FXS is thought to enhance our knowledge of the pathophysiology of ASD. Accumulated evidence implicates deficits in the inhibitory circuits in FXS that tips E–I balance toward excitation. Deficits in interneurons, the main source of an inhibitory neurotransmitter, gamma-aminobutyric acid (GABA), have been reported in FXS, including a reduced number of cells, reduction in intrinsic cellular excitability, or weaker synaptic connectivity. Manipulating the interneuron activity ameliorated the symptoms in the FXS mouse model, which makes it reasonable to conceptualize FXS as an interneuronopathy. While it is still poorly understood how the developmental profiles of the inhibitory circuit go awry in FXS, recent works have uncovered several developmental alterations in the functional properties of interneurons. Correcting disrupted E–I balance by potentiating the inhibitory circuit by targeting interneurons may have a therapeutic potential in FXS. I will review the recent evidence about the inhibitory alterations and interneuron dysfunction in ASD and FXS and will discuss the future directions of this field.https://www.mdpi.com/2073-4409/10/10/2610autismfragile X syndromeinterneuronGABAE–I balance |
| spellingShingle | Toshihiro Nomura Interneuron Dysfunction and Inhibitory Deficits in Autism and Fragile X Syndrome Cells autism fragile X syndrome interneuron GABA E–I balance |
| title | Interneuron Dysfunction and Inhibitory Deficits in Autism and Fragile X Syndrome |
| title_full | Interneuron Dysfunction and Inhibitory Deficits in Autism and Fragile X Syndrome |
| title_fullStr | Interneuron Dysfunction and Inhibitory Deficits in Autism and Fragile X Syndrome |
| title_full_unstemmed | Interneuron Dysfunction and Inhibitory Deficits in Autism and Fragile X Syndrome |
| title_short | Interneuron Dysfunction and Inhibitory Deficits in Autism and Fragile X Syndrome |
| title_sort | interneuron dysfunction and inhibitory deficits in autism and fragile x syndrome |
| topic | autism fragile X syndrome interneuron GABA E–I balance |
| url | https://www.mdpi.com/2073-4409/10/10/2610 |
| work_keys_str_mv | AT toshihironomura interneurondysfunctionandinhibitorydeficitsinautismandfragilexsyndrome |