title: The polyunsaturated fatty acids, EPA and DPA exert a protective effect in the hippocampus of the aged rat.
abstract: 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.
authors.affiliation: Trinity College Institute for Neuroscience, Dublin, Ireland.
authors.forename: Laura
authors.initials: L
authors.lastname: Kelly
authors.forename: Belinda
authors.initials: B
authors.lastname: Grehan
authors.forename: Andrea Della
authors.initials: AD
authors.lastname: Chiesa
authors.forename: Shane M
authors.initials: SM
authors.lastname: O'Mara
authors.forename: Eric
authors.initials: E
authors.lastname: Downer
authors.forename: George
authors.initials: G
authors.lastname: Sahyoun
authors.forename: Karen A
authors.initials: KA
authors.lastname: Massey
authors.forename: Anna
authors.initials: A
authors.lastname: Nicolaou
authors.forename: Marina A
authors.initials: MA
authors.lastname: Lynch
mesh_terms: 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
chemical_list: D005231:Fatty Acids, Unsaturated; D018696:Neuroprotective Agents; D015118:Eicosapentaenoic Acid; C026219:docosapentaenoic acid