Planned intervention: On Thursday March 28th 07:00 UTC Zenodo will be unavailable for up to 5 minutes to perform a database upgrade.
Published October 3, 2015 | Version v1
Journal article Open

The L-type calcium channel Cav1.3 is required for proper hippocampal neurogenesis and cognitive functions.

  • 1. Institute of Molecular Regenerative Medicine, Paracelsus Medical University, Salzburg, Austria and Spinal Cord Injury and Tissue Regeneration Center Salzburg (SCI-TReCS), Paracelsus Medical University, Salzburg, Austria
  • 2. Department of Pharmacology and Toxicology, Institute of Pharmacy and CMBI, Leopold-Franzens-University of Innsbruck, Innsbruck, Austria
  • 3. Spinal Cord Injury and Tissue Regeneration Center Salzburg (SCI-TReCS), Paracelsus Medical University, Salzburg, Austria and Institute of Experimental Neuroregeneration, Paracelsus Medical University, Salzburg, Austria
  • 4. Department of Molecular Biology, Central Institute of Mental Health and Medical Faculty Mannheim, Heidelberg University, Mannheim, Germany

Description

L-type voltage gated Ca(2+) channels (LTCCs) are widely expressed within different brain regions including the hippocampus. The isoforms Cav1.2 and Cav1.3 have been shown to be involved in hippocampus-dependent learning and memory, cognitive functions that require proper hippocampal neurogenesis. In vitro, functional LTCCs are expressed on neuronal progenitor cells, where they promote neuronal differentiation. Expression of LTCCs on neural stem and progenitor cells within the neurogenic regions in the adult brain in vivo has not been examined so far, and a contribution of the individual isoforms Cav1.2 and Cav1.3 to adult neurogenesis remained to be clarified. To reveal the role of these channels we first evaluated the expression patterns of Cav1.2 and Cav1.3 in the hippocampal dentate gyrus and the subventricular zone (SVZ) in adult (2- and 3-month old) and middle-aged (15-month old) mice on mRNA and protein levels. We performed immunohistological analysis of hippocampal neurogenesis in adult and middle-aged Cav1.3(-/-) mice and finally addressed the importance of Cav1.3 for hippocampal function by evaluating spatial memory and depression-like behavior in adult Cav1.3(-/-) mice. Our results showed Cav1.2 and Cav1.3 expression at different stages of neuronal differentiation. While Cav1.2 was primarily restricted to mature NeuN(+) granular neurons, Cav1.3 was expressed in Nestin(+) neural stem cells and in mature NeuN(+) granular neurons. Adult and middle-aged Cav1.3(-/-) mice showed severe impairments in dentate gyrus neurogenesis, with significantly smaller dentate gyrus volume, reduced survival of newly generated cells, and reduced neuronal differentiation. Further, Cav1.3(-/-) mice showed impairment in the hippocampus dependent object location memory test, implicating Cav1.3 as an essential element for hippocampus-associated cognitive functions. Thus, modulation of LTCC activities may have a crucial impact on neurogenic responses and cognition, which should be considered for future therapeutic administration of LTCCs modulators.

Files

Marschallinger_CellCalcium_2015-P3-AAM.pdf

Files (12.8 MB)

Name Size Download all
md5:9a773547d6e83a7b3a3443293b3ecd7c
12.8 MB Preview Download

Additional details

Funding

INMIND – Imaging of Neuroinflammation in Neurodegenerative Diseases 278850
European Commission