ArticleNeurobiology of aging2010
Hippocampal 'zipper' slice studies reveal a necessary role for calcineurin in the increased activity of L-type Ca(2+) channels with aging.
Article in Neurobiology of aging, 2010. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 26 papers.
What it found
Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.
The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
26 citing papers in PubMed, 40 citations in OpenAlex.
- Calcineurin inhibition may prevent Alzheimer disease in people with Down syndrome.Alzheimer's & dementia : the journal of the Alzheimer's Association · 2025Review
- Development of a monoclonal antibody specific for a calpain-generated ∆48 kDa calcineurin fragment, a marker of distressed astrocytes.Journal of neuroscience methods · 2024Article
- Presynaptic L-Type CaThe Journal of neuroscience : the official journal of the Society for Neuroscience · 2020Article
- Danger: High Voltage-The Role of Voltage-Gated Calcium Channels in Central Nervous System Pathology.Cells · 2017Review
- Calcineurin proteolysis in astrocytes: Implications for impaired synaptic function.Biochimica et biophysica acta · 2016Article
- A Novel Small Molecule Modulator of Amyloid Pathology.Journal of Alzheimer's disease : JAD · 2016Article
- Pycnogenol protects CA3-CA1 synaptic function in a rat model of traumatic brain injury.Experimental neurology · 2016Article
- FK506-binding protein 1b/12.6: a key to aging-related hippocampal Ca2+ dysregulation?European journal of pharmacology · 2014Review
- Calcineurin and glial signaling: neuroinflammation and beyond.Journal of neuroinflammation · 2014Review
- Article
- Calcium dysregulation and neuroinflammation: discrete and integrated mechanisms for age-related synaptic dysfunction.Ageing research reviews · 2013Review
- Targeting astrocytes ameliorates neurologic changes in a mouse model of Alzheimer's disease.The Journal of neuroscience : the official journal of the Society for Neuroscience · 2012Article
- Hypoxia enhances high-voltage-activated calcium currents in rat primary cortical neurons via calcineurin.Epilepsy research · 2012Article
- BDNF upregulation rescues synaptic plasticity in middle-aged ovariectomized rats.Neurobiology of aging · 2012Article
- Reduction in neuronal L-type calcium channel activity in a double knock-in mouse model of Alzheimer's disease.Biochimica et biophysica acta · 2012Article
- Inhibition of soluble tumor necrosis factor ameliorates synaptic alterations and Ca2+ dysregulation in aged rats.PloS one · 2012Article
- A role for calcineurin in Alzheimer's disease.Current neuropharmacology · 2011Article
- Calcium binding protein-mediated regulation of voltage-gated calcium channels linked to human diseases.Acta pharmacologica Sinica · 2011Review
- Preparation of acute hippocampal slices from rats and transgenic mice for the study of synaptic alterations during aging and amyloid pathology.Journal of visualized experiments : JoVE · 2011Article
- Article
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
7 authors at 1 institution in 1 country.
Funding
Abstract
Previous studies have shown that inhibition of the Ca(2+)-/calmodulin-dependent protein phosphatase calcineurin (CN) blocks L-type voltage sensitive Ca(2+) channel (L-VSCC) activity in cultured hippocampal neurons. However, it is not known whether CN contributes to the increase in hippocampal L-VSCC activity that occurs with aging in at least some mammalian species. It is also unclear whether CN's necessary role in VSCC activity is simply permissive or is directly enhancing. To resolve these questions, we used partially dissociated hippocampal "zipper" slices to conduct cell-attached patch recording and RT-PCR on largely intact single neurons from young-adult, mid-aged, and aged rats. Further, we tested for direct CN enhancement of L-VSCCs using virally mediated infection of cultured neurons with an activated form of CN. Similar to previous work, L-VSCC activity was elevated in CA1 neurons of mid-aged and aged rats relative to young adults. The CN inhibitor, FK-506 (5muM) completely blocked the aging-related increase in VSCC activity, reducing the activity level in aged rat neurons to that in younger rat neurons. However, aging was not associated with an increase in neuronal CN mRNA expression, nor was CN expression correlated with VSCC activity. Delivery of activated CN to primary hippocampal cultures induced an increase in neuronal L-VSCC activity but did not elevate L-VSCC protein levels. Together, the results provide the first evidence that CN activity, but not increased expression, plays a selective and necessary role in the aging-related increase in available L-VSCCs, possibly by direct activation. Thus, these studies point to altered CN function as a novel and potentially key factor in aging-dependent neuronal Ca(2+) dysregulation.
Indexed as
Identifiers
What OpenQuestion holds
Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.