PMID- 19215725
OWN - NLM
STAT- MEDLINE
DCOM- 20090820
LR  - 20141120
IS  - 1873-7544 (Electronic)
IS  - 0306-4522 (Linking)
VI  - 159
IP  - 4
DP  - 2009 Apr 10
TI  - Impaired presynaptic cytosolic and mitochondrial calcium dynamics in aged 
      compared to young adult hippocampal CA1 synapses ameliorated by calcium 
      chelation.
PG  - 1300-8
LID - 10.1016/j.neuroscience.2008.12.057 [doi]
AB  - Impaired regulation of presynaptic intracellular calcium is thought to adversely 
      affect synaptic plasticity and cognition in the aged brain. We studied 
      presynaptic cytosolic and mitochondrial calcium (Ca) dynamics using axonally 
      loaded Calcium Green-AM and Rhod-2 AM fluorescence respectively in young (2-3 
      months) and aged (23-26 months) CA3 to CA1 Schaffer collateral excitatory 
      synapses in hippocampal brain slices from Fisher 344 rats. After a tetanus (100 
      Hz, 200 ms), the presynaptic cytosolic Ca peaked at approximately 10 s in the 
      young and approximately 12 s in the aged synapses. Administration of the membrane 
      permeant Ca chelator, bis (O-aminophenoxy)-ethane-N,N,N,N-tetraacetic acid 
      (BAPTA-AM), significantly attenuated the Ca response in the aged slices, but not 
      in the young slices. The presynaptic mitochondrial Ca signal was much slower, 
      peaking at approximately 90 s in both young and aged synapses, returning to 
      baseline by 300 s. BAPTA-AM significantly attenuated the mitochondrial calcium 
      signal only in the young synapses. Uncoupling mitochondrial respiration by 
      carbonyl cyanide m-chlorophenylhydrazone (CCCP) application evoked a massive 
      intracellular cytosolic Ca increase and a significant drop of mitochondrial Ca, 
      especially in aged slices wherein the cytosolic Ca signal disappeared after 
      approximately 150 s of washout and the mitochondrial Ca signal disappeared after 
      25 s of washout. These signals were preserved in aged slices by BAPTA-AM. Five 
      minutes of oxygen glucose deprivation (OGD) was associated with a significant 
      increase in cytosolic Ca in both young and aged synapses, which was irreversible 
      in the aged synapses. These responses were significantly attenuated by BAPTA-AM 
      in both the young and aged synapses. These results support the hypothesis that 
      increasing intracellular calcium neuronal buffering in aged rats ameliorates 
      age-related impaired presynaptic Ca regulation.
FAU - Tonkikh, A A
AU  - Tonkikh AA
AD  - Division of Fundamental Neurobiology, Toronto Western Research Institute, 
      University Health Network, Toronto, Ontario, Canada.
FAU - Carlen, P L
AU  - Carlen PL
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20090106
PL  - United States
TA  - Neuroscience
JT  - Neuroscience
JID - 7605074
RN  - 0 (Central Nervous System Agents)
RN  - 0 (Chelating Agents)
RN  - 139890-68-9 (1,2-bis(2-aminophenoxy)ethane N,N,N',N'-tetraacetic acid 
      acetoxymethyl ester)
RN  - 526U7A2651 (Egtazic Acid)
RN  - 555-60-2 (Carbonyl Cyanide m-Chlorophenyl Hydrazone)
RN  - IY9XDZ35W2 (Glucose)
RN  - SY7Q814VUP (Calcium)
SB  - IM
MH  - *Aging
MH  - Animals
MH  - Calcium/*metabolism
MH  - Carbonyl Cyanide m-Chlorophenyl Hydrazone/administration & dosage
MH  - Cell Hypoxia/physiology
MH  - Central Nervous System Agents/administration & dosage
MH  - Chelating Agents/administration & dosage
MH  - Cytoplasm/drug effects/*metabolism
MH  - Egtazic Acid/administration & dosage/analogs & derivatives
MH  - Electron Transport/drug effects
MH  - Excitatory Postsynaptic Potentials/drug effects/physiology
MH  - Glucose/deficiency
MH  - Hippocampus/drug effects/*metabolism
MH  - In Vitro Techniques
MH  - Mitochondria/drug effects/*metabolism
MH  - Presynaptic Terminals/drug effects/*metabolism
MH  - Rats
MH  - Rats, Inbred F344
MH  - Synapses/drug effects/metabolism
EDAT- 2009/02/14 09:00
MHDA- 2009/08/21 09:00
CRDT- 2009/02/14 09:00
PHST- 2008/11/27 00:00 [received]
PHST- 2008/12/17 00:00 [revised]
PHST- 2008/12/18 00:00 [accepted]
PHST- 2009/02/14 09:00 [entrez]
PHST- 2009/02/14 09:00 [pubmed]
PHST- 2009/08/21 09:00 [medline]
AID - S0306-4522(08)01846-0 [pii]
AID - 10.1016/j.neuroscience.2008.12.057 [doi]
PST - ppublish
SO  - Neuroscience. 2009 Apr 10;159(4):1300-8. doi: 10.1016/j.neuroscience.2008.12.057. 
      Epub 2009 Jan 6.