PMID- 29041816
OWN - NLM
STAT- In-Data-Review
LR  - 20180803
IS  - 1468-2982 (Electronic)
IS  - 0333-1024 (Linking)
VI  - 38
IP  - 9
DP  - 2018 Aug
TI  - Enhanced susceptibility to cortical spreading depression in two types of
      Na(+),K(+)-ATPase alpha2 subunit-deficient mice as a model of familial hemiplegic
      migraine 2.
PG  - 1515-1524
LID - 10.1177/0333102417738249 [doi]
AB  - Background Patients with familial hemiplegic migraine type 2 (FHM2) have a
      mutated ATP1A2 gene (encoding Na(+),K(+)-ATPase alpha2 subunit) and show
      prolonged migraine aura. Cortical spreading depression (CSD), which involves mass
      depolarization of neurons and astrocytes that propagates slowly through the gray 
      matter, is profoundly related to aura. Methods In two types of Atp1a2-defective
      heterozygous mice, Atp1a2(tm1Kwk) (C-KO) and Atp1a2(tm2Kwk) (N-KO), the
      sensitivity and responsiveness to CSD were examined under urethane anesthesia.
      Results In both cases, heterozygotes exhibited a low threshold for induction of
      CSD, faster propagation rate, slower recovery from DC deflection, and profound
      suppression of the electroencephalogram, compared to wild-type mice. A high dose 
      of KCl elicited repeated CSDs for a longer period, with a tendency for a greater 
      frequency of CSD occurrence in heterozygotes. The difference of every endpoint
      was slightly greater in N-KO than C-KO. Change of regional cerebral blood flow in
      response to CSD showed no significant difference. Conclusion Heterozygotes of
      Atp1a2-defective mice simulating FHM2 demonstrated high susceptibility to CSD
      rather than cortical vasoreactivity, and these effects may differ depending upon 
      the knockout strategy for the gene disruption. These results suggest that
      patients with FHM2 may exhibit high susceptibility to CSD, resulting in migraine.
FAU - Unekawa, Miyuki
AU  - Unekawa M
AD  - 1 Department of Neurology, Keio University School of Medicine, Tokyo, Japan.
FAU - Ikeda, Keiko
AU  - Ikeda K
AD  - 2 Division of Biology, Hyogo College of Medicine, Nishinomiya, Japan.
AD  - 3 Division of Biology, Center for Molecular Medicine, Jichi Medical School,
      Shimotsuke, Japan.
FAU - Tomita, Yutaka
AU  - Tomita Y
AD  - 1 Department of Neurology, Keio University School of Medicine, Tokyo, Japan.
FAU - Kawakami, Kiyoshi
AU  - Kawakami K
AD  - 3 Division of Biology, Center for Molecular Medicine, Jichi Medical School,
      Shimotsuke, Japan.
FAU - Suzuki, Norihiro
AU  - Suzuki N
AD  - 1 Department of Neurology, Keio University School of Medicine, Tokyo, Japan.
LA  - eng
PT  - Journal Article
DEP - 20171017
PL  - England
TA  - Cephalalgia
JT  - Cephalalgia : an international journal of headache
JID - 8200710
OTO - NOTNLM
OT  - Atp1a2
OT  - K+-ATPase alpha2 subunit
OT  - Na+
OT  - cortical spreading depression
OT  - familial hemiplegic migraine 2
EDAT- 2017/10/19 06:00
MHDA- 2017/10/19 06:00
CRDT- 2017/10/19 06:00
PHST- 2017/10/19 06:00 [pubmed]
PHST- 2017/10/19 06:00 [medline]
PHST- 2017/10/19 06:00 [entrez]
AID - 10.1177/0333102417738249 [doi]
PST - ppublish
SO  - Cephalalgia. 2018 Aug;38(9):1515-1524. doi: 10.1177/0333102417738249. Epub 2017
      Oct 17.