PMID- 34790098
OWN - NLM
STAT- PubMed-not-MEDLINE
LR  - 20211119
IS  - 1662-5102 (Print)
IS  - 1662-5102 (Electronic)
IS  - 1662-5102 (Linking)
VI  - 15
DP  - 2021
TI  - Targeting CDK5 in Astrocytes Promotes Calcium Homeostasis Under Excitotoxic 
      Conditions.
PG  - 643717
LID - 10.3389/fncel.2021.643717 [doi]
LID - 643717
AB  - Glutamate excitotoxicity triggers overactivation of CDK5 and increases calcium 
      influx in neural cells, which promotes dendritic retraction, spine loss, 
      increased mitochondrial calcium from the endoplasmic reticulum, and neuronal 
      death. Our previous studies showed that CDK5 knockdown (KD) in astrocytes 
      improves neurovascular integrity and cognitive functions and exerts 
      neuroprotective effects. However, how CDK5-targeted astrocytes affect calcium 
      regulation and whether this phenomenon is associated with changes in neuronal 
      plasticity have not yet been analyzed. In this study, CDK5 KD astrocytes 
      transplanted in CA3 remained at the injection site without proliferation, 
      regulated calcium in the CA1 hippocampal region after excitotoxicity by glutamate 
      in ex vivo hippocampal slices, improving synapsin and PSD95 clustering. These 
      CDK5 KD astrocytes induced astrocyte stellation and neuroprotection after 
      excitotoxicity induced by glutamate in vitro. Also, these effects were supported 
      by CDK5 inhibition (CDK5i) in vitro through intracellular stabilization of 
      calcium levels in astrocytes. Additionally, these cells in cocultures restored 
      calcium homeostasis in neurons, redistributing calcium from somas to dendrites, 
      accompanied by dendrite branching, higher dendritic spines and synapsin-PSD95 
      clustering. In summary, induction of calcium homeostasis at the CA1 hippocampal 
      area by CDK5 KD astrocytes transplanted in the CA3 area highlights the role of 
      astrocytes as a cell therapy target due to CDK5-KD astrocyte-mediated synaptic 
      clustering, calcium spreading regulation between both areas, and recovery of the 
      intracellular astrocyte-neuron calcium imbalance and plasticity impairment 
      generated by glutamate excitotoxicity.
CI  - Copyright (c) 2021 Toro-Fernandez, Zuluaga-Monares, Saldarriaga-Cartagena, 
      Cardona-Gomez and Posada-Duque.
FAU - Toro-Fernandez, Luisa Fernanda
AU  - Toro-Fernandez LF
AD  - Instituto de Biologia, Facultad de Ciencias Exactas y Naturales, Universidad de 
      Antioquia, Medellin, Colombia.
AD  - Area de Neurobiologia Celular y Molecular, Grupo de Neurociencias de Antioquia, 
      Universidad de Antioquia, Medellin, Colombia.
FAU - Zuluaga-Monares, Juan Camilo
AU  - Zuluaga-Monares JC
AD  - Instituto de Biologia, Facultad de Ciencias Exactas y Naturales, Universidad de 
      Antioquia, Medellin, Colombia.
AD  - Area de Neurobiologia Celular y Molecular, Grupo de Neurociencias de Antioquia, 
      Universidad de Antioquia, Medellin, Colombia.
FAU - Saldarriaga-Cartagena, Ana Maria
AU  - Saldarriaga-Cartagena AM
AD  - Instituto de Biologia, Facultad de Ciencias Exactas y Naturales, Universidad de 
      Antioquia, Medellin, Colombia.
AD  - Area de Neurobiologia Celular y Molecular, Grupo de Neurociencias de Antioquia, 
      Universidad de Antioquia, Medellin, Colombia.
FAU - Cardona-Gomez, Gloria Patricia
AU  - Cardona-Gomez GP
AD  - Area de Neurobiologia Celular y Molecular, Grupo de Neurociencias de Antioquia, 
      Universidad de Antioquia, Medellin, Colombia.
FAU - Posada-Duque, Rafael
AU  - Posada-Duque R
AD  - Instituto de Biologia, Facultad de Ciencias Exactas y Naturales, Universidad de 
      Antioquia, Medellin, Colombia.
AD  - Area de Neurobiologia Celular y Molecular, Grupo de Neurociencias de Antioquia, 
      Universidad de Antioquia, Medellin, Colombia.
LA  - eng
PT  - Journal Article
DEP - 20211101
PL  - Switzerland
TA  - Front Cell Neurosci
JT  - Frontiers in cellular neuroscience
JID - 101477935
PMC - PMC8591049
OTO - NOTNLM
OT  - CDK5
OT  - astrocyte
OT  - calcium homeostasis
OT  - excitotoxicity
OT  - hippocampus
OT  - synaptic protein
COIS- The authors declare that the research was conducted in the absence of any 
      commercial or financial relationships that could be construed as a potential 
      conflict of interest.
EDAT- 2021/11/19 06:00
MHDA- 2021/11/19 06:01
PMCR- 2021/01/01
CRDT- 2021/11/18 06:56
PHST- 2020/12/21 00:00 [received]
PHST- 2021/10/05 00:00 [accepted]
PHST- 2021/11/18 06:56 [entrez]
PHST- 2021/11/19 06:00 [pubmed]
PHST- 2021/11/19 06:01 [medline]
PHST- 2021/01/01 00:00 [pmc-release]
AID - 10.3389/fncel.2021.643717 [doi]
PST - epublish
SO  - Front Cell Neurosci. 2021 Nov 1;15:643717. doi: 10.3389/fncel.2021.643717. 
      eCollection 2021.