PMID- 36899880
OWN - NLM
STAT- MEDLINE
DCOM- 20230314
LR  - 20230327
IS  - 2073-4409 (Electronic)
IS  - 2073-4409 (Linking)
VI  - 12
IP  - 5
DP  - 2023 Feb 25
TI  - Heparan Sulfates Regulate Axonal Excitability and Context Generalization through 
      Ca(2+)/Calmodulin-Dependent Protein Kinase II.
LID - 10.3390/cells12050744 [doi]
LID - 744
AB  - Our previous studies demonstrated that enzymatic removal of highly sulfated 
      heparan sulfates with heparinase 1 impaired axonal excitability and reduced 
      expression of ankyrin G at the axon initial segments in the CA1 region of the 
      hippocampus ex vivo, impaired context discrimination in vivo, and increased 
      Ca(2+)/calmodulin-dependent protein kinase II (CaMKII) activity in vitro. Here, 
      we show that in vivo delivery of heparinase 1 in the CA1 region of the 
      hippocampus elevated autophosphorylation of CaMKII 24 h after injection in mice. 
      Patch clamp recording in CA1 neurons revealed no significant heparinase effects 
      on the amplitude or frequency of miniature excitatory and inhibitory postsynaptic 
      currents, while the threshold for action potential generation was increased and 
      fewer spikes were generated in response to current injection. Delivery of 
      heparinase on the next day after contextual fear conditioning induced context 
      overgeneralization 24 h after injection. Co-administration of heparinase with the 
      CaMKII inhibitor (autocamtide-2-related inhibitory peptide) rescued neuronal 
      excitability and expression of ankyrin G at the axon initial segment. It also 
      restored context discrimination, suggesting the key role of CaMKII in neuronal 
      signaling downstream of heparan sulfate proteoglycans and highlighting a link 
      between impaired CA1 pyramidal cell excitability and context generalization 
      during recall of contextual memories.
FAU - Song, Inseon
AU  - Song I
AD  - Molecular Neuroplasticity Group, German Center for Neurodegenerative Diseases 
      (DZNE), 39120 Magdeburg, Germany.
FAU - Kuznetsova, Tatiana
AU  - Kuznetsova T
AD  - Department of Integrative Medical Biology, Umea University, 90187 Umea, Sweden.
FAU - Baidoe-Ansah, David
AU  - Baidoe-Ansah D
AD  - Molecular Neuroplasticity Group, German Center for Neurodegenerative Diseases 
      (DZNE), 39120 Magdeburg, Germany.
FAU - Mirzapourdelavar, Hadi
AU  - Mirzapourdelavar H
AD  - Molecular Neuroplasticity Group, German Center for Neurodegenerative Diseases 
      (DZNE), 39120 Magdeburg, Germany.
FAU - Senkov, Oleg
AU  - Senkov O
AD  - Molecular Neuroplasticity Group, German Center for Neurodegenerative Diseases 
      (DZNE), 39120 Magdeburg, Germany.
FAU - Hayani, Hussam
AU  - Hayani H
AD  - Molecular Neuroplasticity Group, German Center for Neurodegenerative Diseases 
      (DZNE), 39120 Magdeburg, Germany.
FAU - Mironov, Andrey
AU  - Mironov A
AD  - Molecular Neuroplasticity Group, German Center for Neurodegenerative Diseases 
      (DZNE), 39120 Magdeburg, Germany.
FAU - Kaushik, Rahul
AU  - Kaushik R
AD  - Molecular Neuroplasticity Group, German Center for Neurodegenerative Diseases 
      (DZNE), 39120 Magdeburg, Germany.
FAU - Druzin, Michael
AU  - Druzin M
AD  - Department of Integrative Medical Biology, Umea University, 90187 Umea, Sweden.
FAU - Johansson, Staffan
AU  - Johansson S
AUID- ORCID: 0000-0003-1022-5097
AD  - Department of Integrative Medical Biology, Umea University, 90187 Umea, Sweden.
FAU - Dityatev, Alexander
AU  - Dityatev A
AUID- ORCID: 0000-0002-0472-0553
AD  - Molecular Neuroplasticity Group, German Center for Neurodegenerative Diseases 
      (DZNE), 39120 Magdeburg, Germany.
AD  - Medizinische Fakultat, Otto-von-Guricke-Universitat Magdeburg, 39120 Magdeburg, 
      Germany.
AD  - Center for Behavioral Brain Sciences (CBBS), 39106 Magdeburg, Germany.
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20230225
PL  - Switzerland
TA  - Cells
JT  - Cells
JID - 101600052
RN  - 0 (Ankyrins)
RN  - EC 2.7.11.17 (Calcium-Calmodulin-Dependent Protein Kinase Type 2)
RN  - EC 4.2.2.7 (Heparin Lyase)
RN  - 9050-30-0 (Heparitin Sulfate)
RN  - EC 2.7.11.17 (Camk2g protein, mouse)
SB  - IM
MH  - Animals
MH  - Mice
MH  - Ankyrins/metabolism
MH  - *Calcium-Calmodulin-Dependent Protein Kinase Type 2/metabolism
MH  - Heparin Lyase/metabolism/pharmacology
MH  - *Heparitin Sulfate/metabolism
MH  - Hippocampus/metabolism
PMC - PMC10000602
OTO - NOTNLM
OT  - ankyrin G
OT  - axon initial segment
OT  - axonal excitability
OT  - context discrimination
OT  - extracellular matrix
OT  - synaptic plasticity
COIS- A.D. is Editor-in-Chief of the section Cell Microenvironment in Cells. The other 
      authors declare that they have no competing interest.
EDAT- 2023/03/12 06:00
MHDA- 2023/03/15 06:00
PMCR- 2023/02/25
CRDT- 2023/03/11 01:03
PHST- 2023/02/01 00:00 [received]
PHST- 2023/02/21 00:00 [revised]
PHST- 2023/02/23 00:00 [accepted]
PHST- 2023/03/11 01:03 [entrez]
PHST- 2023/03/12 06:00 [pubmed]
PHST- 2023/03/15 06:00 [medline]
PHST- 2023/02/25 00:00 [pmc-release]
AID - cells12050744 [pii]
AID - cells-12-00744 [pii]
AID - 10.3390/cells12050744 [doi]
PST - epublish
SO  - Cells. 2023 Feb 25;12(5):744. doi: 10.3390/cells12050744.