Cargando…
Neuropathological investigation of patients with prolonged anorexia nervosa
OBJECTIVES: Recent neuroimaging studies have indicated that the mesolimbic pathway, known to work as reward neuronal circuitry, regulates cognitive–behavioral flexibility in prolonged anorexia nervosa (AN). Although AN is associated with the highest mortality rate among psychiatric disorders, there...
Autores principales: | , , , , , , , , , , |
---|---|
Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
John Wiley & Sons Australia, Ltd
2022
|
Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9314851/ https://www.ncbi.nlm.nih.gov/pubmed/35167165 http://dx.doi.org/10.1111/pcn.13340 |
_version_ | 1784754417510121472 |
---|---|
author | Kawakami, Ito Iritani, Shuji Riku, Yuichi Umeda, Kentaro Takase, Mina Ikeda, Kenji Niizato, Kazuhiro Arai, Tomio Yoshida, Mari Oshima, Kenichi Hasegawa, Masato |
author_facet | Kawakami, Ito Iritani, Shuji Riku, Yuichi Umeda, Kentaro Takase, Mina Ikeda, Kenji Niizato, Kazuhiro Arai, Tomio Yoshida, Mari Oshima, Kenichi Hasegawa, Masato |
author_sort | Kawakami, Ito |
collection | PubMed |
description | OBJECTIVES: Recent neuroimaging studies have indicated that the mesolimbic pathway, known to work as reward neuronal circuitry, regulates cognitive–behavioral flexibility in prolonged anorexia nervosa (AN). Although AN is associated with the highest mortality rate among psychiatric disorders, there have been few neuropathological studies on this topic. This study aims to identify alterations of the reward circuitry regions, especially in the nucleus accumbens (NAcc), using AN brain tissues. METHODS: The neuronal networks in AN cases and controls were examined by immunohistochemistry directed at tyrosine hydroxylase (TH; dopaminergic neuron marker) and glial fibrillary acidic protein (GFAP; astrocyte marker). We also immunochemically analyzed frozen samples presenting astrogliosis, especially in the NAcc and striatum. RESULTS: Histologically, neuronal deformation with cytoplasmic shrinkage was seen in reward‐related brain regions, such as the orbitofrontal cortex/anterior cingulate cortex. The NAcc showed massive GFAP‐positive astrocytes and dot‐like protrusions of astrocytes in the shell compartment. In the shell, TH and GFAP immunoreactivities revealed prominent astrogliosis within striosomes, which receive projection from the ventral tegmental area (VTA). The numbers of GFAP‐positive astrocytes in the NAcc (P = 0.0079) and VTA (P = 0.0025) of AN cases were significantly higher than those of controls. Strongly immunoreactive 18 to 25 kDa bands, which might represent degradation products, were detected only in the NAcc of AN cases. Clinically, all cases presented cognitive rigidity, which might reflect a deficit of the reward pathway. CONCLUSION: Our findings suggest impaired dopaminergic innervation between the NAcc and VTA in AN. Functional dysconnectivity in the reward‐related network might induce neuropsychiatric symptoms associated with AN. |
format | Online Article Text |
id | pubmed-9314851 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2022 |
publisher | John Wiley & Sons Australia, Ltd |
record_format | MEDLINE/PubMed |
spelling | pubmed-93148512022-07-30 Neuropathological investigation of patients with prolonged anorexia nervosa Kawakami, Ito Iritani, Shuji Riku, Yuichi Umeda, Kentaro Takase, Mina Ikeda, Kenji Niizato, Kazuhiro Arai, Tomio Yoshida, Mari Oshima, Kenichi Hasegawa, Masato Psychiatry Clin Neurosci Regular Articles OBJECTIVES: Recent neuroimaging studies have indicated that the mesolimbic pathway, known to work as reward neuronal circuitry, regulates cognitive–behavioral flexibility in prolonged anorexia nervosa (AN). Although AN is associated with the highest mortality rate among psychiatric disorders, there have been few neuropathological studies on this topic. This study aims to identify alterations of the reward circuitry regions, especially in the nucleus accumbens (NAcc), using AN brain tissues. METHODS: The neuronal networks in AN cases and controls were examined by immunohistochemistry directed at tyrosine hydroxylase (TH; dopaminergic neuron marker) and glial fibrillary acidic protein (GFAP; astrocyte marker). We also immunochemically analyzed frozen samples presenting astrogliosis, especially in the NAcc and striatum. RESULTS: Histologically, neuronal deformation with cytoplasmic shrinkage was seen in reward‐related brain regions, such as the orbitofrontal cortex/anterior cingulate cortex. The NAcc showed massive GFAP‐positive astrocytes and dot‐like protrusions of astrocytes in the shell compartment. In the shell, TH and GFAP immunoreactivities revealed prominent astrogliosis within striosomes, which receive projection from the ventral tegmental area (VTA). The numbers of GFAP‐positive astrocytes in the NAcc (P = 0.0079) and VTA (P = 0.0025) of AN cases were significantly higher than those of controls. Strongly immunoreactive 18 to 25 kDa bands, which might represent degradation products, were detected only in the NAcc of AN cases. Clinically, all cases presented cognitive rigidity, which might reflect a deficit of the reward pathway. CONCLUSION: Our findings suggest impaired dopaminergic innervation between the NAcc and VTA in AN. Functional dysconnectivity in the reward‐related network might induce neuropsychiatric symptoms associated with AN. John Wiley & Sons Australia, Ltd 2022-03-07 2022-05 /pmc/articles/PMC9314851/ /pubmed/35167165 http://dx.doi.org/10.1111/pcn.13340 Text en © 2022 The Authors. Psychiatry and Clinical Neurosciences published by John Wiley & Sons Australia, Ltd on behalf of Japanese Society of Psychiatry and Neurology. https://creativecommons.org/licenses/by-nc-nd/4.0/This is an open access article under the terms of the http://creativecommons.org/licenses/by-nc-nd/4.0/ (https://creativecommons.org/licenses/by-nc-nd/4.0/) License, which permits use and distribution in any medium, provided the original work is properly cited, the use is non‐commercial and no modifications or adaptations are made. |
spellingShingle | Regular Articles Kawakami, Ito Iritani, Shuji Riku, Yuichi Umeda, Kentaro Takase, Mina Ikeda, Kenji Niizato, Kazuhiro Arai, Tomio Yoshida, Mari Oshima, Kenichi Hasegawa, Masato Neuropathological investigation of patients with prolonged anorexia nervosa |
title | Neuropathological investigation of patients with prolonged anorexia nervosa |
title_full | Neuropathological investigation of patients with prolonged anorexia nervosa |
title_fullStr | Neuropathological investigation of patients with prolonged anorexia nervosa |
title_full_unstemmed | Neuropathological investigation of patients with prolonged anorexia nervosa |
title_short | Neuropathological investigation of patients with prolonged anorexia nervosa |
title_sort | neuropathological investigation of patients with prolonged anorexia nervosa |
topic | Regular Articles |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9314851/ https://www.ncbi.nlm.nih.gov/pubmed/35167165 http://dx.doi.org/10.1111/pcn.13340 |
work_keys_str_mv | AT kawakamiito neuropathologicalinvestigationofpatientswithprolongedanorexianervosa AT iritanishuji neuropathologicalinvestigationofpatientswithprolongedanorexianervosa AT rikuyuichi neuropathologicalinvestigationofpatientswithprolongedanorexianervosa AT umedakentaro neuropathologicalinvestigationofpatientswithprolongedanorexianervosa AT takasemina neuropathologicalinvestigationofpatientswithprolongedanorexianervosa AT ikedakenji neuropathologicalinvestigationofpatientswithprolongedanorexianervosa AT niizatokazuhiro neuropathologicalinvestigationofpatientswithprolongedanorexianervosa AT araitomio neuropathologicalinvestigationofpatientswithprolongedanorexianervosa AT yoshidamari neuropathologicalinvestigationofpatientswithprolongedanorexianervosa AT oshimakenichi neuropathologicalinvestigationofpatientswithprolongedanorexianervosa AT hasegawamasato neuropathologicalinvestigationofpatientswithprolongedanorexianervosa |