Search: onr:"swepub:oai:DiVA.org:uu-478311" >
Elevated endogenous...
Elevated endogenous GDNF induces altered dopamine signalling in mice and correlates with clinical severity in schizophrenia.
-
- Mätlik, Kärt (author)
- University of Helsinki
-
- Garton, Daniel R (author)
- University of Helsinki
-
- Montaño-Rodríguez, Ana R (author)
- University of Helsinki
-
show more...
-
- Olfat, Soophie (author)
- Karolinska Institutet,Karolinska Institute,University of Helsinki
-
- Eren, Feride (author)
- Karolinska Institutet,Karolinska Institute
-
- Casserly, Laoise (author)
- University of Helsinki
-
- Damdimopoulos, Anastasios (author)
- Karolinska Institutet,Karolinska Institute
-
- Panhelainen, Anne (author)
- University of Helsinki
-
- Porokuokka, L Lauriina (author)
- University of Helsinki
-
- Jakobsson, Johan (author)
- Karolinska Institutet,Lund University,Lunds universitet,Molekylär neurogenetik,Forskargrupper vid Lunds universitet,Molecular Neurogenetics,Lund University Research Groups
-
- Turconi, Giorgio (author)
- University of Helsinki
-
- Schweizer, Nadine (author)
- Karolinska Institute
-
- Bereczki, Erika (author)
- Karolinska Institutet,Karolinska Institute
-
- Piehl, Fredrik (author)
- Karolinska University Hospital
-
- Engberg, Göran (author)
- Karolinska Institutet,Karolinska Institute
-
- Cervenka, Simon (author)
- Karolinska Institutet,Uppsala University,Karolinska Institute,Uppsala universitet,Psykiatri
-
- Piepponen, T Petteri (author)
- University of Helsinki
-
- Zhang, Fu-Ping (author)
- University of Helsinki,University of Turku
-
- Sipilä, Petra (author)
- University of Turku
-
Jakobsson, Johan (author)
-
- Sellgren, Carl M (author)
- Karolinska Institutet,Karolinska Institute
-
- Erhardt, Sophie (author)
- Karolinska Institutet,Karolinska Institute
-
- Andressoo, Jaan-Olle (author)
- Karolinska Institute,University of Helsinki
-
show less...
-
(creator_code:org_t)
- 2022-05-26
- 2022
- English.
-
In: Molecular Psychiatry. - : Springer Nature. - 1359-4184 .- 1476-5578.
- Related links:
-
https://doi.org/10.1...
-
show more...
-
https://uu.diva-port... (primary) (Raw object)
-
http://dx.doi.org/10... (free)
-
https://urn.kb.se/re...
-
https://doi.org/10.1...
-
https://lup.lub.lu.s...
-
http://kipublication...
-
show less...
Abstract
Subject headings
Close
- Presynaptic increase in striatal dopamine is the primary dopaminergic abnormality in schizophrenia, but the underlying mechanisms are not understood. Here, we hypothesized that increased expression of endogenous GDNF could induce dopaminergic abnormalities that resemble those seen in schizophrenia. To test the impact of GDNF elevation, without inducing adverse effects caused by ectopic overexpression, we developed a novel in vivo approach to conditionally increase endogenous GDNF expression. We found that a 2-3-fold increase in endogenous GDNF in the brain was sufficient to induce molecular, cellular, and functional changes in dopamine signalling in the striatum and prefrontal cortex, including increased striatal presynaptic dopamine levels and reduction of dopamine in prefrontal cortex. Mechanistically, we identified adenosine A2a receptor (A2AR), a G-protein coupled receptor that modulates dopaminergic signalling, as a possible mediator of GDNF-driven dopaminergic abnormalities. We further showed that pharmacological inhibition of A2AR with istradefylline partially normalised striatal GDNF and striatal and cortical dopamine levels in mice. Lastly, we found that GDNF levels are increased in the cerebrospinal fluid of first episode psychosis patients, and in post-mortem striatum of schizophrenia patients. Our results reveal a possible contributor for increased striatal dopamine signalling in a subgroup of schizophrenia patients and suggest that GDNF-A2AR crosstalk may regulate dopamine function in a therapeutically targetable manner.
Subject headings
- MEDICIN OCH HÄLSOVETENSKAP -- Klinisk medicin -- Psykiatri (hsv//swe)
- MEDICAL AND HEALTH SCIENCES -- Clinical Medicine -- Psychiatry (hsv//eng)
- MEDICIN OCH HÄLSOVETENSKAP -- Medicinska och farmaceutiska grundvetenskaper -- Neurovetenskaper (hsv//swe)
- MEDICAL AND HEALTH SCIENCES -- Basic Medicine -- Neurosciences (hsv//eng)
Publication and Content Type
- ref (subject category)
- art (subject category)
Find in a library
To the university's database
- By the author/editor
-
Mätlik, Kärt
-
Garton, Daniel R
-
Montaño-Rodrígue ...
-
Olfat, Soophie
-
Eren, Feride
-
Casserly, Laoise
-
show more...
-
Damdimopoulos, A ...
-
Panhelainen, Ann ...
-
Porokuokka, L La ...
-
Jakobsson, Johan
-
Turconi, Giorgio
-
Schweizer, Nadin ...
-
Bereczki, Erika
-
Piehl, Fredrik
-
Engberg, Göran
-
Cervenka, Simon
-
Piepponen, T Pet ...
-
Zhang, Fu-Ping
-
Sipilä, Petra
-
Sellgren, Carl M
-
Erhardt, Sophie
-
Andressoo, Jaan- ...
-
show less...
- About the subject
-
- MEDICAL AND HEALTH SCIENCES
-
MEDICAL AND HEAL ...
-
and Clinical Medicin ...
-
and Psychiatry
-
- MEDICAL AND HEALTH SCIENCES
-
MEDICAL AND HEAL ...
-
and Basic Medicine
-
and Neurosciences
- Articles in the publication
-
Molecular Psychi ...
- By the university
-
Uppsala University
-
Lund University
-
Karolinska Institutet