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PGC-1 alpha Signali...
PGC-1 alpha Signaling Increases GABA(A) Receptor Subunit alpha 2 Expression, GABAergic Neurotransmission and Anxiety-Like Behavior in Mice
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- Vanaveski, Taavi (author)
- Univ Helsinki, Finland; Minerva Fdn, Finland; Univ Tartu, Estonia; Quretec Ltd, Estonia
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- Molchanova, Svetlana (author)
- Univ Helsinki, Finland
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- Duc Pham, Dan (author)
- Univ Helsinki, Finland; Minerva Fdn, Finland
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- Schafer, Annika (author)
- Univ Helsinki, Finland; Minerva Fdn, Finland
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- Pajanoja, Ceren (author)
- Univ Helsinki, Finland; Minerva Fdn, Finland
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- Narvik, Jane (author)
- Univ Tartu, Estonia; Quretec Ltd, Estonia
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- Srinivasan, Vignesh (author)
- Univ Helsinki, Finland; Minerva Fdn, Finland
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- Urb, Mari (author)
- Protobios LCC, Estonia
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- Koivisto, Maria (author)
- Univ Helsinki, Finland; Minerva Fdn, Finland
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- Vasar, Eero (author)
- Univ Tartu, Estonia
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- Timmusk, Tonis (author)
- Protobios LCC, Estonia; Tallinn Univ Technol, Estonia
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- Minkeviciene, Rimante (author)
- Minerva Fdn, Finland
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- Eriksson, Ove (author)
- Univ Helsinki, Finland
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- Lalowski, Maciej (author)
- Univ Helsinki, Finland; Univ Helsinki, Finland; Polish Acad Sci, Poland
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- Taira, Tomi (author)
- Univ Helsinki, Finland
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- Korhonen, Laura (author)
- Linköpings universitet,Centrum för social och affektiv neurovetenskap,Medicinska fakulteten,Region Östergötland, Barn- och ungdomspsykiatriska kliniken Linköping
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- Voikar, Vootele (author)
- Univ Helsinki, Finland
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- Lindholm, Dan (author)
- Univ Helsinki, Finland; Minerva Fdn, Finland
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(creator_code:org_t)
- 2021-02-01
- 2021
- English.
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In: Frontiers in Molecular Neuroscience. - : FRONTIERS MEDIA SA. - 1662-5099. ; 14
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Abstract
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- Peroxisome proliferator-activated receptor-gamma coactivator-1 alpha (PGC-1 alpha) is a master regulator of mitochondria biogenesis and cell stress playing a role in metabolic and degenerative diseases. In the brain PGC-1 alpha expression has been localized mainly to GABAergic interneurons but its overall role is not fully understood. We observed here that the protein levels of gamma-aminobutyric acid (GABA) type A receptor-alpha 2 subunit (GABAR alpha 2) were increased in hippocampus and brain cortex in transgenic (Tg) mice overexpressing PGC-1 alpha in neurons. Along with this, GABAR alpha 2 expression was enhanced in the hippocampus of the PGC-1 alpha Tg mice, as shown by quantitative PCR. Double immunostaining revealed that GABAR alpha 2 co-localized with the synaptic protein gephyrin in higher amounts in the striatum radiatum layer of the hippocampal CA1 region in the Tg compared with Wt mice. Electrophysiology revealed that the frequency of spontaneous and miniature inhibitory postsynaptic currents (mIPSCs) was increased in the CA1 region in the Tg mice, indicative of an augmented GABAergic transmission. Behavioral tests revealed an increase for anxiety-like behavior in the PGC-1 alpha Tg mice compared with controls. To study whether drugs acting on PPAR gamma can affect GABAR alpha 2, we employed pioglitazone that elevated GABAR alpha 2 expression in primary cultured neurons. Similar results were obtained using the specific PPAR gamma agonist, N-(2-benzoylphenyl)-O-[2-(methyl-2-pyridinylamino) ethyl]-L-tyrosine hydrate (GW1929). These results demonstrate that PGC-1 alpha regulates GABAR alpha 2 subunits and GABAergic neurotransmission in the hippocampus with behavioral consequences. This indicates further that drugs like pioglitazone, widely used in the treatment of type 2 diabetes, can influence GABAR alpha 2 expression via the PPAR gamma/PGC-1 alpha system.
Subject headings
- MEDICIN OCH HÄLSOVETENSKAP -- Medicinska och farmaceutiska grundvetenskaper -- Neurovetenskaper (hsv//swe)
- MEDICAL AND HEALTH SCIENCES -- Basic Medicine -- Neurosciences (hsv//eng)
Keyword
- GABA-A receptors; PGC-1α PPARγ pioglitazone; gene expression; neurotransmission; anxiety; behavioral test
Publication and Content Type
- ref (subject category)
- art (subject category)
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- By the author/editor
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Vanaveski, Taavi
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Molchanova, Svet ...
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Duc Pham, Dan
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Schafer, Annika
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Pajanoja, Ceren
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Narvik, Jane
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show more...
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Srinivasan, Vign ...
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Urb, Mari
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Koivisto, Maria
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Vasar, Eero
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Timmusk, Tonis
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Minkeviciene, Ri ...
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Eriksson, Ove
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Lalowski, Maciej
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Taira, Tomi
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Korhonen, Laura
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Voikar, Vootele
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Lindholm, Dan
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show less...
- About the subject
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- MEDICAL AND HEALTH SCIENCES
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MEDICAL AND HEAL ...
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and Basic Medicine
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and Neurosciences
- Articles in the publication
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Frontiers in Mol ...
- By the university
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Linköping University