Hippocampal injury and cognitive impairments are common after cardiac arrest and stroke and do not have an effective intervention despite much effort. Therefore, we developed a new approach aimed at reversing synaptic dysfunction by targeting TRPM2 channels. Cardiac arrest/cardiopulmonary resuscitation (CA/CPR) in mice was used to investigate cognitive deficits and the role of the calcium-permeable ion channel transient receptor potential-M2 (TRPM2) in ischemia-induced synaptic dysfunction. Our data indicates that absence (TRPM2(-/-)) or acute inhibition of TRPM2 channels with tatM2NX reduced hippocampal cell death in males only, but prevented synaptic plasticity deficits in both sexes. Remarkably, administration of tatM2NX weeks after injury reversed hippocampal plasticity and memory deficits. Finally, TRPM2-dependent activation of calcineurin-GSK3 beta pathway contributes to synaptic plasticity impairments. These data suggest persistent TRPM2 activity following ischemia contributes to impairments of the surviving hippocampal network and that inhibition of TRPM2 channels at chronic time points may represent a novel strategy to improve functional recovery following cerebral ischemia that is independent of neuroprotection.
机构:
Toronto Western Hosp, Res Inst, Toronto, ON M5T 2S8, Canada
Univ Toronto, Dept Physiol, Toronto, ON M5S 1A8, CanadaToronto Western Hosp, Res Inst, Toronto, ON M5T 2S8, Canada
Alim, Ishraq
;
Teves, Lucy
论文数: 0引用数: 0
h-index: 0
机构:
Toronto Western Hosp, Res Inst, Toronto, ON M5T 2S8, CanadaToronto Western Hosp, Res Inst, Toronto, ON M5T 2S8, Canada
Teves, Lucy
;
Li, Rongwen
论文数: 0引用数: 0
h-index: 0
机构:
Toronto Western Hosp, Res Inst, Toronto, ON M5T 2S8, CanadaToronto Western Hosp, Res Inst, Toronto, ON M5T 2S8, Canada
Li, Rongwen
;
Mori, Yasuo
论文数: 0引用数: 0
h-index: 0
机构:
Kyoto Univ, Dept Synthet Chem & Biol Chem, Grad Sch Engn, Nishikyo Ku, Kyoto 6158510, JapanToronto Western Hosp, Res Inst, Toronto, ON M5T 2S8, Canada
Mori, Yasuo
;
Tymianski, Michael
论文数: 0引用数: 0
h-index: 0
机构:
Toronto Western Hosp, Res Inst, Toronto, ON M5T 2S8, Canada
Univ Toronto, Dept Physiol, Toronto, ON M5S 1A8, Canada
Univ Toronto, Dept Surg Neurosurg, Toronto, ON M5S 1A8, CanadaToronto Western Hosp, Res Inst, Toronto, ON M5T 2S8, Canada
机构:
Univ Amsterdam, Acad Med Ctr, Dept Cardiol, NL-1105 AZ Amsterdam, NetherlandsUniv Amsterdam, Acad Med Ctr, Dept Cardiol, NL-1105 AZ Amsterdam, Netherlands
Beesems, Stefanie G.
;
Wittebrood, Kim M.
论文数: 0引用数: 0
h-index: 0
机构:
Univ Amsterdam, Acad Med Ctr, Dept Cardiol, NL-1105 AZ Amsterdam, NetherlandsUniv Amsterdam, Acad Med Ctr, Dept Cardiol, NL-1105 AZ Amsterdam, Netherlands
Wittebrood, Kim M.
;
de Haan, Rob J.
论文数: 0引用数: 0
h-index: 0
机构:
Univ Amsterdam, Acad Med Ctr, Clin Res Unit, NL-1105 AZ Amsterdam, NetherlandsUniv Amsterdam, Acad Med Ctr, Dept Cardiol, NL-1105 AZ Amsterdam, Netherlands
de Haan, Rob J.
;
Koster, Rudolph W.
论文数: 0引用数: 0
h-index: 0
机构:
Univ Amsterdam, Acad Med Ctr, Dept Cardiol, NL-1105 AZ Amsterdam, NetherlandsUniv Amsterdam, Acad Med Ctr, Dept Cardiol, NL-1105 AZ Amsterdam, Netherlands
机构:
Univ Calif Los Angeles, Dept Neurol, David Geffen Sch Med, Los Angeles, CA 90095 USAUniv Calif Los Angeles, Dept Neurol, David Geffen Sch Med, Los Angeles, CA 90095 USA
机构:
Univ Calif Los Angeles, David Geffen Sch Med, Dept Neurol, Los Angeles, CA 90095 USAUniv Calif Los Angeles, David Geffen Sch Med, Dept Neurol, Los Angeles, CA 90095 USA
Clarkson, Andrew N.
;
Huang, Ben S.
论文数: 0引用数: 0
h-index: 0
机构:
Univ Calif Los Angeles, David Geffen Sch Med, Dept Neurol, Los Angeles, CA 90095 USA
Univ Calif Los Angeles, David Geffen Sch Med, Interdept PhD Program Neurosci, Los Angeles, CA 90095 USAUniv Calif Los Angeles, David Geffen Sch Med, Dept Neurol, Los Angeles, CA 90095 USA
Huang, Ben S.
;
MacIsaac, Sarah E.
论文数: 0引用数: 0
h-index: 0
机构:
Univ Calif Los Angeles, David Geffen Sch Med, Dept Neurol, Los Angeles, CA 90095 USAUniv Calif Los Angeles, David Geffen Sch Med, Dept Neurol, Los Angeles, CA 90095 USA
MacIsaac, Sarah E.
;
Mody, Istvan
论文数: 0引用数: 0
h-index: 0
机构:
Univ Calif Los Angeles, David Geffen Sch Med, Dept Neurol, Los Angeles, CA 90095 USA
Univ Calif Los Angeles, David Geffen Sch Med, Interdept PhD Program Neurosci, Los Angeles, CA 90095 USA
Univ Calif Los Angeles, David Geffen Sch Med, Dept Physiol, Los Angeles, CA 90095 USAUniv Calif Los Angeles, David Geffen Sch Med, Dept Neurol, Los Angeles, CA 90095 USA
Mody, Istvan
;
Carmichael, S. Thomas
论文数: 0引用数: 0
h-index: 0
机构:
Univ Calif Los Angeles, David Geffen Sch Med, Dept Neurol, Los Angeles, CA 90095 USAUniv Calif Los Angeles, David Geffen Sch Med, Dept Neurol, Los Angeles, CA 90095 USA
机构:
Univ Walk, Sch Med Sci, Dept Anat, MRC Ctr Synapt Plast, Bristol BS8 1TD, Avon, England
Univ British Columbia, Dept Psychiat, Brain Res Ctr, Vancouver, BC V6T 1Z3, Canada
Seoul Natl Univ, Dept Brain & Cognit Sci, Seoul 151747, South KoreaUniv Walk, Sch Med Sci, Dept Anat, MRC Ctr Synapt Plast, Bristol BS8 1TD, Avon, England
Collingridge, Graham L.
;
Peineau, Stephane
论文数: 0引用数: 0
h-index: 0
机构:
Univ Walk, Sch Med Sci, Dept Anat, MRC Ctr Synapt Plast, Bristol BS8 1TD, Avon, England
Hop Robert Debre, INSERM, U676, F-75019 Paris, France
Univ Paris 07, Fac Med Denis Diderot, Paris, France
PremUP, Paris, FranceUniv Walk, Sch Med Sci, Dept Anat, MRC Ctr Synapt Plast, Bristol BS8 1TD, Avon, England
Peineau, Stephane
;
Howland, John G.
论文数: 0引用数: 0
h-index: 0
机构:
Univ Saskatchewan, Dept Psychol, Neural Syst & Plast Res Grp, Saskatoon, SK S7N 5A5, Canada
Univ Saskatchewan, Dept Physiol, Neural Syst & Plast Res Grp, Saskatoon, SK S7N 5A5, CanadaUniv Walk, Sch Med Sci, Dept Anat, MRC Ctr Synapt Plast, Bristol BS8 1TD, Avon, England
Howland, John G.
;
Wang, Yu Tian
论文数: 0引用数: 0
h-index: 0
机构:
Univ British Columbia, Dept Med, Coastal Hlth Res Inst, Brain Res Ctr, Vancouver, BC V6T 2B5, Canada
China Med Univ Hosp, Ctr Neuropsychiat, Taichung, Taiwan
China Med Univ Hosp, Grad Inst Immunol, Taichung, TaiwanUniv Walk, Sch Med Sci, Dept Anat, MRC Ctr Synapt Plast, Bristol BS8 1TD, Avon, England
机构:
Toronto Western Hosp, Res Inst, Toronto, ON M5T 2S8, Canada
Univ Toronto, Dept Physiol, Toronto, ON M5S 1A8, CanadaToronto Western Hosp, Res Inst, Toronto, ON M5T 2S8, Canada
Alim, Ishraq
;
Teves, Lucy
论文数: 0引用数: 0
h-index: 0
机构:
Toronto Western Hosp, Res Inst, Toronto, ON M5T 2S8, CanadaToronto Western Hosp, Res Inst, Toronto, ON M5T 2S8, Canada
Teves, Lucy
;
Li, Rongwen
论文数: 0引用数: 0
h-index: 0
机构:
Toronto Western Hosp, Res Inst, Toronto, ON M5T 2S8, CanadaToronto Western Hosp, Res Inst, Toronto, ON M5T 2S8, Canada
Li, Rongwen
;
Mori, Yasuo
论文数: 0引用数: 0
h-index: 0
机构:
Kyoto Univ, Dept Synthet Chem & Biol Chem, Grad Sch Engn, Nishikyo Ku, Kyoto 6158510, JapanToronto Western Hosp, Res Inst, Toronto, ON M5T 2S8, Canada
Mori, Yasuo
;
Tymianski, Michael
论文数: 0引用数: 0
h-index: 0
机构:
Toronto Western Hosp, Res Inst, Toronto, ON M5T 2S8, Canada
Univ Toronto, Dept Physiol, Toronto, ON M5S 1A8, Canada
Univ Toronto, Dept Surg Neurosurg, Toronto, ON M5S 1A8, CanadaToronto Western Hosp, Res Inst, Toronto, ON M5T 2S8, Canada
机构:
Univ Amsterdam, Acad Med Ctr, Dept Cardiol, NL-1105 AZ Amsterdam, NetherlandsUniv Amsterdam, Acad Med Ctr, Dept Cardiol, NL-1105 AZ Amsterdam, Netherlands
Beesems, Stefanie G.
;
Wittebrood, Kim M.
论文数: 0引用数: 0
h-index: 0
机构:
Univ Amsterdam, Acad Med Ctr, Dept Cardiol, NL-1105 AZ Amsterdam, NetherlandsUniv Amsterdam, Acad Med Ctr, Dept Cardiol, NL-1105 AZ Amsterdam, Netherlands
Wittebrood, Kim M.
;
de Haan, Rob J.
论文数: 0引用数: 0
h-index: 0
机构:
Univ Amsterdam, Acad Med Ctr, Clin Res Unit, NL-1105 AZ Amsterdam, NetherlandsUniv Amsterdam, Acad Med Ctr, Dept Cardiol, NL-1105 AZ Amsterdam, Netherlands
de Haan, Rob J.
;
Koster, Rudolph W.
论文数: 0引用数: 0
h-index: 0
机构:
Univ Amsterdam, Acad Med Ctr, Dept Cardiol, NL-1105 AZ Amsterdam, NetherlandsUniv Amsterdam, Acad Med Ctr, Dept Cardiol, NL-1105 AZ Amsterdam, Netherlands
机构:
Univ Calif Los Angeles, Dept Neurol, David Geffen Sch Med, Los Angeles, CA 90095 USAUniv Calif Los Angeles, Dept Neurol, David Geffen Sch Med, Los Angeles, CA 90095 USA
机构:
Univ Calif Los Angeles, David Geffen Sch Med, Dept Neurol, Los Angeles, CA 90095 USAUniv Calif Los Angeles, David Geffen Sch Med, Dept Neurol, Los Angeles, CA 90095 USA
Clarkson, Andrew N.
;
Huang, Ben S.
论文数: 0引用数: 0
h-index: 0
机构:
Univ Calif Los Angeles, David Geffen Sch Med, Dept Neurol, Los Angeles, CA 90095 USA
Univ Calif Los Angeles, David Geffen Sch Med, Interdept PhD Program Neurosci, Los Angeles, CA 90095 USAUniv Calif Los Angeles, David Geffen Sch Med, Dept Neurol, Los Angeles, CA 90095 USA
Huang, Ben S.
;
MacIsaac, Sarah E.
论文数: 0引用数: 0
h-index: 0
机构:
Univ Calif Los Angeles, David Geffen Sch Med, Dept Neurol, Los Angeles, CA 90095 USAUniv Calif Los Angeles, David Geffen Sch Med, Dept Neurol, Los Angeles, CA 90095 USA
MacIsaac, Sarah E.
;
Mody, Istvan
论文数: 0引用数: 0
h-index: 0
机构:
Univ Calif Los Angeles, David Geffen Sch Med, Dept Neurol, Los Angeles, CA 90095 USA
Univ Calif Los Angeles, David Geffen Sch Med, Interdept PhD Program Neurosci, Los Angeles, CA 90095 USA
Univ Calif Los Angeles, David Geffen Sch Med, Dept Physiol, Los Angeles, CA 90095 USAUniv Calif Los Angeles, David Geffen Sch Med, Dept Neurol, Los Angeles, CA 90095 USA
Mody, Istvan
;
Carmichael, S. Thomas
论文数: 0引用数: 0
h-index: 0
机构:
Univ Calif Los Angeles, David Geffen Sch Med, Dept Neurol, Los Angeles, CA 90095 USAUniv Calif Los Angeles, David Geffen Sch Med, Dept Neurol, Los Angeles, CA 90095 USA
机构:
Univ Walk, Sch Med Sci, Dept Anat, MRC Ctr Synapt Plast, Bristol BS8 1TD, Avon, England
Univ British Columbia, Dept Psychiat, Brain Res Ctr, Vancouver, BC V6T 1Z3, Canada
Seoul Natl Univ, Dept Brain & Cognit Sci, Seoul 151747, South KoreaUniv Walk, Sch Med Sci, Dept Anat, MRC Ctr Synapt Plast, Bristol BS8 1TD, Avon, England
Collingridge, Graham L.
;
Peineau, Stephane
论文数: 0引用数: 0
h-index: 0
机构:
Univ Walk, Sch Med Sci, Dept Anat, MRC Ctr Synapt Plast, Bristol BS8 1TD, Avon, England
Hop Robert Debre, INSERM, U676, F-75019 Paris, France
Univ Paris 07, Fac Med Denis Diderot, Paris, France
PremUP, Paris, FranceUniv Walk, Sch Med Sci, Dept Anat, MRC Ctr Synapt Plast, Bristol BS8 1TD, Avon, England
Peineau, Stephane
;
Howland, John G.
论文数: 0引用数: 0
h-index: 0
机构:
Univ Saskatchewan, Dept Psychol, Neural Syst & Plast Res Grp, Saskatoon, SK S7N 5A5, Canada
Univ Saskatchewan, Dept Physiol, Neural Syst & Plast Res Grp, Saskatoon, SK S7N 5A5, CanadaUniv Walk, Sch Med Sci, Dept Anat, MRC Ctr Synapt Plast, Bristol BS8 1TD, Avon, England
Howland, John G.
;
Wang, Yu Tian
论文数: 0引用数: 0
h-index: 0
机构:
Univ British Columbia, Dept Med, Coastal Hlth Res Inst, Brain Res Ctr, Vancouver, BC V6T 2B5, Canada
China Med Univ Hosp, Ctr Neuropsychiat, Taichung, Taiwan
China Med Univ Hosp, Grad Inst Immunol, Taichung, TaiwanUniv Walk, Sch Med Sci, Dept Anat, MRC Ctr Synapt Plast, Bristol BS8 1TD, Avon, England