Transient knockdown of tyrosine hydroxylase during development has persistent effects on behaviour in adult zebrafish (Danio rerio).
Abnormal dopamine (DA) signaling is often suggested as causative in schizophrenia. The other prominent hypothesis for this disorder, largely driven by epidemiological data, is that certain adverse events during the early stages of brain development increase an individual's risk of developing sc...
Guardado en:
Autores principales: | , , , , , , , |
---|---|
Formato: | article |
Lenguaje: | EN |
Publicado: |
Public Library of Science (PLoS)
2012
|
Materias: | |
Acceso en línea: | https://doaj.org/article/e83618ddfce84680a83faebd012d93ea |
Etiquetas: |
Agregar Etiqueta
Sin Etiquetas, Sea el primero en etiquetar este registro!
|
id |
oai:doaj.org-article:e83618ddfce84680a83faebd012d93ea |
---|---|
record_format |
dspace |
spelling |
oai:doaj.org-article:e83618ddfce84680a83faebd012d93ea2021-11-18T07:09:45ZTransient knockdown of tyrosine hydroxylase during development has persistent effects on behaviour in adult zebrafish (Danio rerio).1932-620310.1371/journal.pone.0042482https://doaj.org/article/e83618ddfce84680a83faebd012d93ea2012-01-01T00:00:00Zhttps://www.ncbi.nlm.nih.gov/pmc/articles/pmid/22879998/?tool=EBIhttps://doaj.org/toc/1932-6203Abnormal dopamine (DA) signaling is often suggested as causative in schizophrenia. The other prominent hypothesis for this disorder, largely driven by epidemiological data, is that certain adverse events during the early stages of brain development increase an individual's risk of developing schizophrenia later in life. However, the clinical and preclinical literature consistently implicates behavioural, cognitive, and pharmacological abnormalities, implying that DA signaling is abnormal in the adult brain. How can we reconcile these two major hypotheses underlying much of the clinical and basic research into schizophrenia? In this study we have transiently knocked down tyrosine hydroxylase (TH, the rate limiting enzyme in DA synthesis) gene expression in the early stages of brain development in zebrafish using morpholinos. We show that by adulthood, TH and DA levels have returned to normal and basic DA-mediated behaviours, such as locomotion, are also normal. However, when they were exposed to a novel environment the levels of freezing and immediate positioning in deeper zones were significantly reduced in these adult fish. The neurochemistry underlying these behaviours is complex, and the exact mechanisms for these abnormal behaviours remains unknown. This study demonstrates that early transient alterations in DA ontogeny can produce persistent alterations in adult brain function and suggests that the zebrafish may be a promising model animal for future studies directed at clarifying the basic neurodevelopmental mechanisms behind complex psychiatric disease.Isabel FormellaEthan K ScottTom H J BurneLauren R HarmsPei-Yun LiuKarly M TurnerXiaoying CuiDarryl W EylesPublic Library of Science (PLoS)articleMedicineRScienceQENPLoS ONE, Vol 7, Iss 8, p e42482 (2012) |
institution |
DOAJ |
collection |
DOAJ |
language |
EN |
topic |
Medicine R Science Q |
spellingShingle |
Medicine R Science Q Isabel Formella Ethan K Scott Tom H J Burne Lauren R Harms Pei-Yun Liu Karly M Turner Xiaoying Cui Darryl W Eyles Transient knockdown of tyrosine hydroxylase during development has persistent effects on behaviour in adult zebrafish (Danio rerio). |
description |
Abnormal dopamine (DA) signaling is often suggested as causative in schizophrenia. The other prominent hypothesis for this disorder, largely driven by epidemiological data, is that certain adverse events during the early stages of brain development increase an individual's risk of developing schizophrenia later in life. However, the clinical and preclinical literature consistently implicates behavioural, cognitive, and pharmacological abnormalities, implying that DA signaling is abnormal in the adult brain. How can we reconcile these two major hypotheses underlying much of the clinical and basic research into schizophrenia? In this study we have transiently knocked down tyrosine hydroxylase (TH, the rate limiting enzyme in DA synthesis) gene expression in the early stages of brain development in zebrafish using morpholinos. We show that by adulthood, TH and DA levels have returned to normal and basic DA-mediated behaviours, such as locomotion, are also normal. However, when they were exposed to a novel environment the levels of freezing and immediate positioning in deeper zones were significantly reduced in these adult fish. The neurochemistry underlying these behaviours is complex, and the exact mechanisms for these abnormal behaviours remains unknown. This study demonstrates that early transient alterations in DA ontogeny can produce persistent alterations in adult brain function and suggests that the zebrafish may be a promising model animal for future studies directed at clarifying the basic neurodevelopmental mechanisms behind complex psychiatric disease. |
format |
article |
author |
Isabel Formella Ethan K Scott Tom H J Burne Lauren R Harms Pei-Yun Liu Karly M Turner Xiaoying Cui Darryl W Eyles |
author_facet |
Isabel Formella Ethan K Scott Tom H J Burne Lauren R Harms Pei-Yun Liu Karly M Turner Xiaoying Cui Darryl W Eyles |
author_sort |
Isabel Formella |
title |
Transient knockdown of tyrosine hydroxylase during development has persistent effects on behaviour in adult zebrafish (Danio rerio). |
title_short |
Transient knockdown of tyrosine hydroxylase during development has persistent effects on behaviour in adult zebrafish (Danio rerio). |
title_full |
Transient knockdown of tyrosine hydroxylase during development has persistent effects on behaviour in adult zebrafish (Danio rerio). |
title_fullStr |
Transient knockdown of tyrosine hydroxylase during development has persistent effects on behaviour in adult zebrafish (Danio rerio). |
title_full_unstemmed |
Transient knockdown of tyrosine hydroxylase during development has persistent effects on behaviour in adult zebrafish (Danio rerio). |
title_sort |
transient knockdown of tyrosine hydroxylase during development has persistent effects on behaviour in adult zebrafish (danio rerio). |
publisher |
Public Library of Science (PLoS) |
publishDate |
2012 |
url |
https://doaj.org/article/e83618ddfce84680a83faebd012d93ea |
work_keys_str_mv |
AT isabelformella transientknockdownoftyrosinehydroxylaseduringdevelopmenthaspersistenteffectsonbehaviourinadultzebrafishdaniorerio AT ethankscott transientknockdownoftyrosinehydroxylaseduringdevelopmenthaspersistenteffectsonbehaviourinadultzebrafishdaniorerio AT tomhjburne transientknockdownoftyrosinehydroxylaseduringdevelopmenthaspersistenteffectsonbehaviourinadultzebrafishdaniorerio AT laurenrharms transientknockdownoftyrosinehydroxylaseduringdevelopmenthaspersistenteffectsonbehaviourinadultzebrafishdaniorerio AT peiyunliu transientknockdownoftyrosinehydroxylaseduringdevelopmenthaspersistenteffectsonbehaviourinadultzebrafishdaniorerio AT karlymturner transientknockdownoftyrosinehydroxylaseduringdevelopmenthaspersistenteffectsonbehaviourinadultzebrafishdaniorerio AT xiaoyingcui transientknockdownoftyrosinehydroxylaseduringdevelopmenthaspersistenteffectsonbehaviourinadultzebrafishdaniorerio AT darrylweyles transientknockdownoftyrosinehydroxylaseduringdevelopmenthaspersistenteffectsonbehaviourinadultzebrafishdaniorerio |
_version_ |
1718423888010936320 |