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Translational psychiatry
Jan 17, 2024;14 (1): 29.

Cdk5-dependent rapid formation and stabilization of dendritic spines by corticotropin-releasing factor.

Dorien Vandael, Katlijn Vints, Pieter Baatsen, Małgorzata A Śliwińska, Sergio Gabarre, Lies De Groef, Lieve Moons, Vasily Rybakin, Natalia V Gounko
Author Information
  1. Dorien Vandael: VIB-KU Leuven Center for Brain & Disease Research, Electron Microscopy Platform & VIB-Bioimaging Core, O&N5 Herestraat 49 box 602, 3000, Leuven, Belgium. ORCID
  2. Katlijn Vints: VIB-KU Leuven Center for Brain & Disease Research, Electron Microscopy Platform & VIB-Bioimaging Core, O&N5 Herestraat 49 box 602, 3000, Leuven, Belgium.
  3. Pieter Baatsen: VIB-KU Leuven Center for Brain & Disease Research, Electron Microscopy Platform & VIB-Bioimaging Core, O&N5 Herestraat 49 box 602, 3000, Leuven, Belgium.
  4. Małgorzata A Śliwińska: VIB-KU Leuven Center for Brain & Disease Research, Electron Microscopy Platform & VIB-Bioimaging Core, O&N5 Herestraat 49 box 602, 3000, Leuven, Belgium. ORCID
  5. Sergio Gabarre: VIB-KU Leuven Center for Brain & Disease Research, Electron Microscopy Platform & VIB-Bioimaging Core, O&N5 Herestraat 49 box 602, 3000, Leuven, Belgium. ORCID
  6. Lies De Groef: KU Leuven, Leuven Brain Institute, Department of Biology, Animal Physiology and Neurobiology Division, Naamsestraat 61 box 2464, 3000, Leuven, Belgium.
  7. Lieve Moons: KU Leuven, Leuven Brain Institute, Department of Biology, Animal Physiology and Neurobiology Division, Naamsestraat 61 box 2464, 3000, Leuven, Belgium. ORCID
  8. Vasily Rybakin: National University of Singapore, Department of Microbiology and Immunology, Yng Loo Lin School of Medicine, and Immunology Program, 5 Science Drive 2, Blk MD4, 117545, Singapore, Singapore.
  9. Natalia V Gounko: VIB-KU Leuven Center for Brain & Disease Research, Electron Microscopy Platform & VIB-Bioimaging Core, O&N5 Herestraat 49 box 602, 3000, Leuven, Belgium. ngunko@gmail.com. ORCID
PMID: 38233378 DOI: 10.1038/s41398-024-02749-7

Abstract

The neuropeptide corticotropin-releasing factor (CRF) exerts a pivotal role in modulating neuronal activity in the mammalian brain. The effects of CRF exhibit notable variations, depending on factors such as duration of exposure, concentration, and anatomical location. In the CA1 region of the hippocampus, the impact of CRF is dichotomous: chronic exposure to CRF impairs synapse formation and dendritic integrity, whereas brief exposure enhances synapse formation and plasticity. In the current study, we demonstrate long-term effects of acute CRF on the density and stability of mature mushroom spines ex vivo. We establish that both CRF receptors are present in this hippocampal region, and we pinpoint their precise subcellular localization within synapses by electron microscopy. Furthermore, both in vivo and ex vivo data collectively demonstrate that a transient surge of CRF in the CA1 activates the cyclin-dependent kinase 5 (Cdk5)-pathway. This activation leads to a notable augmentation in CRF-dependent spine formation. Overall, these data suggest that upon acute release of CRF in the CA1-SR synapse, both CRF-Rs can be activated and promote synaptic plasticity via activating different downstream signaling pathways, such as the Cdk5-pathway.

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MeSH Term

Animals
Corticotropin-Releasing Hormone
Dendritic Spines
Cyclin-Dependent Kinase 5
Hippocampus
Receptors, Corticotropin-Releasing Hormone
Synapses
Mammals

Chemicals

Corticotropin-Releasing Hormone
Cyclin-Dependent Kinase 5
Receptors, Corticotropin-Releasing Hormone
Journal Article

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