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Measuring Motor Coordination in Mice
Published on: May 29, 2013
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Two-fold elevation of endogenous GDNF levels in mice improves motor coordination without causing side-effects
Kärt Mätlik1, Vootele Võikar2, Carolina Vilenius3
1Department of Pharmacology, Faculty of Medicine & Helsinki Institute of Life Science, University of Helsinki, Helsinki, Finland.
Scientific Reports
|August 10, 2018
Summary
Increased glial cell line-derived neurotrophic factor (GDNF) in mice improved motor function without adverse behavioral effects. This suggests potential therapeutic benefits for neurological disorders by enhancing dopamine system activity.
Area of Science:
- Neuroscience
- Molecular Biology
- Genetics
Background:
- Glial cell line-derived neurotrophic factor (GDNF) supports dopaminergic neuron survival and is investigated for Parkinson's disease (PD).
- The precise role of endogenous GDNF in dopamine system regulation and behavior remains unclear.
- Ectopic GDNF delivery in PD models has shown side effects, necessitating research into endogenous GDNF modulation.
Purpose of the Study:
- To investigate the impact of increased endogenous GDNF levels on dopamine system function and animal behavior.
- To assess the behavioral outcomes in GDNF hypermorphic mice across various tests, including those relevant to neuropsychiatric disorders.
- To determine if elevated endogenous GDNF offers therapeutic benefits without adverse effects.
Main Methods:
- Generation of GDNF hypermorphic mice (Gdnf wt/hyper) with increased endogenous GDNF expression.
- Biochemical analysis of dopamine levels, dopamine transporter activity, and neuron counts in the nigrostriatal pathway.
- Comprehensive behavioral testing of Gdnf wt/hyper mice using 20 distinct behavioral paradigms.
Main Results:
- Gdnf wt/hyper mice exhibited mild increases in midbrain dopamine neurons and striatal dopaminergic varicosities.
- These mice showed augmented dopamine transporter activity and dopamine levels.
- Despite enhanced dopamine system function, no behavioral differences were observed in psychiatric disease-related phenotypes, but male mice showed improved motor function.
Conclusions:
- Modest elevation of endogenous GDNF levels enhances nigrostriatal dopamine system function and improves motor performance.
- Increased endogenous GDNF does not appear to induce adverse behavioral outcomes or mimic psychiatric disease phenotypes.
- These findings support the potential of endogenous GDNF modulation as a therapeutic strategy for motor-related neurological conditions.
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