Two-fold elevation of endogenous GDNF levels in mice improves motor coordination without causing side-effects

Abstract Glial cell line-derived neurotrophic factor (GDNF) promotes the survival of dopaminergic neurons in vitro and in vivo. For this reason, GDNF is currently in clinical trials for the treatment of Parkinson’s disease (PD). However, how endogenous GDNF influences dopamine system function and an...

Descripción completa

Guardado en:
Detalles Bibliográficos
Autores principales: Kärt Mätlik, Vootele Võikar, Carolina Vilenius, Natalia Kulesskaya, Jaan-Olle Andressoo
Formato: article
Lenguaje:EN
Publicado: Nature Portfolio 2018
Materias:
R
Q
Acceso en línea:https://doaj.org/article/4c8060365899450983ac1b9eea80ab2e
Etiquetas: Agregar Etiqueta
Sin Etiquetas, Sea el primero en etiquetar este registro!
id oai:doaj.org-article:4c8060365899450983ac1b9eea80ab2e
record_format dspace
spelling oai:doaj.org-article:4c8060365899450983ac1b9eea80ab2e2021-12-02T15:09:11ZTwo-fold elevation of endogenous GDNF levels in mice improves motor coordination without causing side-effects10.1038/s41598-018-29988-12045-2322https://doaj.org/article/4c8060365899450983ac1b9eea80ab2e2018-08-01T00:00:00Zhttps://doi.org/10.1038/s41598-018-29988-1https://doaj.org/toc/2045-2322Abstract Glial cell line-derived neurotrophic factor (GDNF) promotes the survival of dopaminergic neurons in vitro and in vivo. For this reason, GDNF is currently in clinical trials for the treatment of Parkinson’s disease (PD). However, how endogenous GDNF influences dopamine system function and animal behavior is not fully understood. We recently generated GDNF hypermorphic mice that express increased levels of endogenous GDNF from the native locus, resulting in augmented function of the nigrostriatal dopamine system. Specifically, Gdnf  wt/hyper mice have a mild increase in striatal and midbrain dopamine levels, increased dopamine transporter activity, and 15% increased numbers of midbrain dopamine neurons and striatal dopaminergic varicosities. Since changes in the dopamine system are implicated in several neuropsychiatric diseases, including schizophrenia, attention deficit hyperactivity disorder (ADHD) and depression, and ectopic GDNF delivery associates with side-effects in PD models and clinical trials, we further investigated Gdnf  wt/hyper mice using 20 behavioral tests. Despite increased dopamine levels, dopamine release and dopamine transporter activity, there were no differences in psychiatric disease related phenotypes. However, compared to controls, male Gdnf  wt/hyper mice performed better in tests measuring motor function. Therefore, a modest elevation of endogenous GDNF levels improves motor function but does not induce adverse behavioral outcomes.Kärt MätlikVootele VõikarCarolina VileniusNatalia KulesskayaJaan-Olle AndressooNature PortfolioarticleMedicineRScienceQENScientific Reports, Vol 8, Iss 1, Pp 1-14 (2018)
institution DOAJ
collection DOAJ
language EN
topic Medicine
R
Science
Q
spellingShingle Medicine
R
Science
Q
Kärt Mätlik
Vootele Võikar
Carolina Vilenius
Natalia Kulesskaya
Jaan-Olle Andressoo
Two-fold elevation of endogenous GDNF levels in mice improves motor coordination without causing side-effects
description Abstract Glial cell line-derived neurotrophic factor (GDNF) promotes the survival of dopaminergic neurons in vitro and in vivo. For this reason, GDNF is currently in clinical trials for the treatment of Parkinson’s disease (PD). However, how endogenous GDNF influences dopamine system function and animal behavior is not fully understood. We recently generated GDNF hypermorphic mice that express increased levels of endogenous GDNF from the native locus, resulting in augmented function of the nigrostriatal dopamine system. Specifically, Gdnf  wt/hyper mice have a mild increase in striatal and midbrain dopamine levels, increased dopamine transporter activity, and 15% increased numbers of midbrain dopamine neurons and striatal dopaminergic varicosities. Since changes in the dopamine system are implicated in several neuropsychiatric diseases, including schizophrenia, attention deficit hyperactivity disorder (ADHD) and depression, and ectopic GDNF delivery associates with side-effects in PD models and clinical trials, we further investigated Gdnf  wt/hyper mice using 20 behavioral tests. Despite increased dopamine levels, dopamine release and dopamine transporter activity, there were no differences in psychiatric disease related phenotypes. However, compared to controls, male Gdnf  wt/hyper mice performed better in tests measuring motor function. Therefore, a modest elevation of endogenous GDNF levels improves motor function but does not induce adverse behavioral outcomes.
format article
author Kärt Mätlik
Vootele Võikar
Carolina Vilenius
Natalia Kulesskaya
Jaan-Olle Andressoo
author_facet Kärt Mätlik
Vootele Võikar
Carolina Vilenius
Natalia Kulesskaya
Jaan-Olle Andressoo
author_sort Kärt Mätlik
title Two-fold elevation of endogenous GDNF levels in mice improves motor coordination without causing side-effects
title_short Two-fold elevation of endogenous GDNF levels in mice improves motor coordination without causing side-effects
title_full Two-fold elevation of endogenous GDNF levels in mice improves motor coordination without causing side-effects
title_fullStr Two-fold elevation of endogenous GDNF levels in mice improves motor coordination without causing side-effects
title_full_unstemmed Two-fold elevation of endogenous GDNF levels in mice improves motor coordination without causing side-effects
title_sort two-fold elevation of endogenous gdnf levels in mice improves motor coordination without causing side-effects
publisher Nature Portfolio
publishDate 2018
url https://doaj.org/article/4c8060365899450983ac1b9eea80ab2e
work_keys_str_mv AT kartmatlik twofoldelevationofendogenousgdnflevelsinmiceimprovesmotorcoordinationwithoutcausingsideeffects
AT vootelevoikar twofoldelevationofendogenousgdnflevelsinmiceimprovesmotorcoordinationwithoutcausingsideeffects
AT carolinavilenius twofoldelevationofendogenousgdnflevelsinmiceimprovesmotorcoordinationwithoutcausingsideeffects
AT nataliakulesskaya twofoldelevationofendogenousgdnflevelsinmiceimprovesmotorcoordinationwithoutcausingsideeffects
AT jaanolleandressoo twofoldelevationofendogenousgdnflevelsinmiceimprovesmotorcoordinationwithoutcausingsideeffects
_version_ 1718387872439992320