The distribution of neuroligin4, an autism-related postsynaptic molecule, in the human brain
Abstract NLGN4X was identified as a single causative gene of rare familial nonsyndromic autism for the first time. It encodes the postsynaptic membrane protein Neuroligin4 (NLGN4), the functions and roles of which, however, are not fully understood due to the lack of a closely homologous gene in rod...
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| Format: | Article |
| Language: | English |
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BMC
2023-02-01
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| Series: | Molecular Brain |
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| Online Access: | https://doi.org/10.1186/s13041-023-00999-y |
| _version_ | 1811165636323180544 |
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| author | Akie Toya Masahide Fukada Eiko Aoki Tohru Matsuki Masashi Ueda Shima Eda Yoshio Hashizume Akio Iio Shigeo Masaki Atsuo Nakayama |
| author_facet | Akie Toya Masahide Fukada Eiko Aoki Tohru Matsuki Masashi Ueda Shima Eda Yoshio Hashizume Akio Iio Shigeo Masaki Atsuo Nakayama |
| author_sort | Akie Toya |
| collection | DOAJ |
| description | Abstract NLGN4X was identified as a single causative gene of rare familial nonsyndromic autism for the first time. It encodes the postsynaptic membrane protein Neuroligin4 (NLGN4), the functions and roles of which, however, are not fully understood due to the lack of a closely homologous gene in rodents. It has been confirmed only recently that human NLGN4 is abundantly expressed in the cerebral cortex and is localized mainly to excitatory synapses. However, the detailed histological distribution of NLGN4, which may have important implications regarding the relationships between NLGN4 and autistic phenotypes, has not been clarified. In this study, we raised specific monoclonal and polyclonal antibodies against NLGN4 and examined the distribution of NLGN4 in developing and developed human brains by immunohistochemistry. We found that, in the brain, NLGN4 is expressed almost exclusively in neurons, in which it has a widespread cytoplasmic pattern of distribution. Among various types of neurons with NLGN4 expression, we identified consistently high expression of NLGN4 in hypothalamic oxytocin (OXT)/vasopressin (AVP)-producing cells. Quantitative analyses revealed that the majority of OXT/AVP-producing neurons expressed NLGN4. NLGN4 signals in other large neurons, such as pyramidal cells in the cerebral cortex and hippocampus as well as neurons in the locus coeruleus and the raphe nucleus, were also remarkable, clearly contrasting with no or scarce signals in Purkinje cells. These data suggest that NLGN4 functions in systems involved in intellectual abilities, social abilities, and sleep and wakefulness, impairments of which are commonly seen in autism. |
| first_indexed | 2024-04-10T15:39:52Z |
| format | Article |
| id | doaj.art-64f35ca121e6410dbeece3b4d1bc9c46 |
| institution | Directory Open Access Journal |
| issn | 1756-6606 |
| language | English |
| last_indexed | 2024-04-10T15:39:52Z |
| publishDate | 2023-02-01 |
| publisher | BMC |
| record_format | Article |
| series | Molecular Brain |
| spelling | doaj.art-64f35ca121e6410dbeece3b4d1bc9c462023-02-12T12:26:15ZengBMCMolecular Brain1756-66062023-02-0116111410.1186/s13041-023-00999-yThe distribution of neuroligin4, an autism-related postsynaptic molecule, in the human brainAkie Toya0Masahide Fukada1Eiko Aoki2Tohru Matsuki3Masashi Ueda4Shima Eda5Yoshio Hashizume6Akio Iio7Shigeo Masaki8Atsuo Nakayama9Department of Cellular Pathology, Institute for Developmental Research, Aichi Developmental Disability CenterDepartment of Cellular Pathology, Institute for Developmental Research, Aichi Developmental Disability CenterDepartment of Cellular Pathology, Institute for Developmental Research, Aichi Developmental Disability CenterDepartment of Cellular Pathology, Institute for Developmental Research, Aichi Developmental Disability CenterDepartment of Cellular Pathology, Institute for Developmental Research, Aichi Developmental Disability CenterDepartment of Cellular Pathology, Institute for Developmental Research, Aichi Developmental Disability CenterInstitute for Medical Science of Aging, Aichi Medical UniversityDepartment of Cellular Pathology, Institute for Developmental Research, Aichi Developmental Disability CenterDepartment of Cellular Pathology, Institute for Developmental Research, Aichi Developmental Disability CenterDepartment of Cellular Pathology, Institute for Developmental Research, Aichi Developmental Disability CenterAbstract NLGN4X was identified as a single causative gene of rare familial nonsyndromic autism for the first time. It encodes the postsynaptic membrane protein Neuroligin4 (NLGN4), the functions and roles of which, however, are not fully understood due to the lack of a closely homologous gene in rodents. It has been confirmed only recently that human NLGN4 is abundantly expressed in the cerebral cortex and is localized mainly to excitatory synapses. However, the detailed histological distribution of NLGN4, which may have important implications regarding the relationships between NLGN4 and autistic phenotypes, has not been clarified. In this study, we raised specific monoclonal and polyclonal antibodies against NLGN4 and examined the distribution of NLGN4 in developing and developed human brains by immunohistochemistry. We found that, in the brain, NLGN4 is expressed almost exclusively in neurons, in which it has a widespread cytoplasmic pattern of distribution. Among various types of neurons with NLGN4 expression, we identified consistently high expression of NLGN4 in hypothalamic oxytocin (OXT)/vasopressin (AVP)-producing cells. Quantitative analyses revealed that the majority of OXT/AVP-producing neurons expressed NLGN4. NLGN4 signals in other large neurons, such as pyramidal cells in the cerebral cortex and hippocampus as well as neurons in the locus coeruleus and the raphe nucleus, were also remarkable, clearly contrasting with no or scarce signals in Purkinje cells. These data suggest that NLGN4 functions in systems involved in intellectual abilities, social abilities, and sleep and wakefulness, impairments of which are commonly seen in autism.https://doi.org/10.1186/s13041-023-00999-yASDNLGN4ImmunohistochemistryPeriventricular nucleusSupraoptic nucleusArginine-vasopressin |
| spellingShingle | Akie Toya Masahide Fukada Eiko Aoki Tohru Matsuki Masashi Ueda Shima Eda Yoshio Hashizume Akio Iio Shigeo Masaki Atsuo Nakayama The distribution of neuroligin4, an autism-related postsynaptic molecule, in the human brain Molecular Brain ASD NLGN4 Immunohistochemistry Periventricular nucleus Supraoptic nucleus Arginine-vasopressin |
| title | The distribution of neuroligin4, an autism-related postsynaptic molecule, in the human brain |
| title_full | The distribution of neuroligin4, an autism-related postsynaptic molecule, in the human brain |
| title_fullStr | The distribution of neuroligin4, an autism-related postsynaptic molecule, in the human brain |
| title_full_unstemmed | The distribution of neuroligin4, an autism-related postsynaptic molecule, in the human brain |
| title_short | The distribution of neuroligin4, an autism-related postsynaptic molecule, in the human brain |
| title_sort | distribution of neuroligin4 an autism related postsynaptic molecule in the human brain |
| topic | ASD NLGN4 Immunohistochemistry Periventricular nucleus Supraoptic nucleus Arginine-vasopressin |
| url | https://doi.org/10.1186/s13041-023-00999-y |
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