The polyunsaturated fatty acids, EPA and DPA exert a protective effect in the hippocampus of the aged rat.
Age is characterized by deficits in synaptic function identified by decreased performance of aged animals in spatial learning tasks and reduced ability of animals to sustain long term potentiation (LTP). Several cellular and molecular events are correlated with these deficits, many of which are indicative of age-related neuroinflammatory and oxidative cell stress. It is significant that agents which decrease microglial activation are commonly associated with restoration of function. We set out to examine whether the n-3 polyunsaturated fatty acid docosapentaenoic acid (DPA), which is a metabolite of eicosapentaenoic acid (EPA), could modulate the age-related increase in microglial activation and the associated increase in oxidative changes and therefore impact on synaptic function in aged rats. We demonstrate that docosapentaenoic acid possesses neurorestorative effects and is capable of downregulating microglial activation. The data show that it also decreases the coupled activation of sphingomyelinase and caspase 3, probably because of its ability to decrease age-related oxidative changes, and consequently attenuates the age-related decrease in spatial learning and long-term potentiation.
Kelly
Laura
L
Trinity College Institute for Neuroscience, Dublin, Ireland.
Grehan
Belinda
B
Chiesa
Andrea Della
AD
O'Mara
Shane M
SM
Downer
Eric
E
Sahyoun
George
G
Massey
Karen A
KA
Nicolaou
Anna
A
Lynch
Marina A
MA
D000375:Aging / Q000187:drug effects / Q000378:metabolism*; D000818:Animals; D002478:Cells, Cultured; D015118:Eicosapentaenoic Acid / Q000008:administration & dosage*; D005231:Fatty Acids, Unsaturated / Q000008:administration & dosage*; D006624:Hippocampus / Q000187:drug effects / Q000201:enzymology / Q000378:metabolism*; D017774:Long-Term Potentiation / Q000187:drug effects / Q000502:physiology; D018782:Maze Learning / Q000187:drug effects / Q000502:physiology; D018696:Neuroprotective Agents / Q000008:administration & dosage*; D018384:Oxidative Stress / Q000187:drug effects / Q000502:physiology; D011897:Random Allocation; D051381:Rats; D017208:Rats, Wistar
D005231:Fatty Acids, Unsaturated; D018696:Neuroprotective Agents; D015118:Eicosapentaenoic Acid; C026219:docosapentaenoic acid