title: Postischemic fish oil treatment restores long-term retrograde memory and dendritic density: An analysis of the time window of efficacy.
abstract: We reported that fish oil (FO) prevented the loss of spatial memory caused by transient, global cerebral ischemia (TGCI), provided the treatment covered the first days prior to and after ischemia. Continuing these studies, trained rats were subjected to TGCI, and FO was administered for 10days, with a time window of efficacy (TWE) of 4, 8 or 12h post-ischemia. Retrograde memory was assessed up to 43days after TGCI. In another experiment, ischemic rats received FO with a 4- or 12-h TWE, and dendritic density was assessed in the hippocampus and cerebral cortex. The brain lipid profile was evaluated in sham-operated and ischemic rats that were treated with FO or vehicle with a 4-h TWE. Ischemia-induced retrograde amnesia was prevented by FO administration that was initiated with either a 4- or 8-h TWE. Fish oil was ineffective after a 12-h TWE. Independent of the TWE, FO did not prevent ischemic neuronal death. In the hippocampus, but not cerebral cortex, TGCI-induced dendritic loss was prevented by FO with a 4-h TWE but not 12-h TWE. The level of docosahexaenoic acid almost doubled in the hippocampus in ischemic, FO-treated rats (4-h TWE). The data indicate that (i) the anti-amnesic effect of FO can be observed with a TWE of up to 8h, (ii) the stimulation of dendritic neuroplasticity may have contributed to this effect, and (iii) DHA in FO may be the main active constituent in FO that mediates the cognitive and neuroplasticity effects on TGCI.
authors.affiliation: Department of Pharmacology and Therapeutics, State University of Maringa, Maringá, Paraná,Brazil.
authors.forename: Cristiano Correia
authors.initials: CC
authors.lastname: Bacarin
authors.affiliation: Department of Pharmacology and Therapeutics, State University of Maringa, Maringá, Paraná,Brazil.
authors.forename: Jaqueline
authors.initials: J
authors.lastname: Godinho
authors.affiliation: Department of Pharmacology and Therapeutics, State University of Maringa, Maringá, Paraná,Brazil.
authors.forename: Rúbia Maria Weffort
authors.initials: RMW
authors.lastname: de Oliveira
authors.affiliation: Department of Chemistry, State University of Maringa, Maringá, Paraná, Brazil.
authors.forename: Makoto
authors.initials: M
authors.lastname: Matsushita
authors.affiliation: Department of Chemistry, State University of Maringa, Maringá, Paraná, Brazil.
authors.forename: Aline Kirie
authors.initials: AK
authors.lastname: Gohara
authors.affiliation: Department of Chemistry Engineering, State University of Maringa, Paraná, Maringá, Brazil.
authors.forename: Lúcio
authors.initials: L
authors.lastname: Cardozo-Filho
authors.affiliation: Department of Chemistry Engineering, State University of Maringa, Paraná, Maringá, Brazil.
authors.forename: Jéssica de Carvalho
authors.initials: JC
authors.lastname: Lima
authors.affiliation: Department of Statistics, State University of Maringa, Maringá, Paraná, Brazil.
authors.forename: Isolde Santos
authors.initials: IS
authors.lastname: Previdelli
authors.affiliation: Department of Morphophysiological Sciences, State University of Maringa, Maringá, Paraná, Brazil.
authors.forename: Silvana Regina
authors.initials: SR
authors.lastname: Melo
authors.affiliation: Federal Technological University of Paraná, Pato Branco, Paraná, Brazil.
authors.forename: Matheus Henrique Dal Molin
authors.initials: MHDM
authors.lastname: Ribeiro
authors.affiliation: Department of Pharmacology and Therapeutics, State University of Maringa, Maringá, Paraná,Brazil. Electronic address: hmilani@uem.br.
authors.forename: Humberto
authors.initials: H
authors.lastname: Milani
mesh_terms: D000648:Amnesia, Retrograde / Q000188:drug therapy / Q000209:etiology / Q000378:metabolism / Q000473:pathology; D000818:Animals; D002540:Cerebral Cortex / Q000187:drug effects / Q000378:metabolism / Q000473:pathology; D003712:Dendrites / Q000187:drug effects* / Q000378:metabolism / Q000473:pathology; D004195:Disease Models, Animal; D004281:Docosahexaenoic Acids / Q000378:metabolism; D005395:Fish Oils / Q000008:administration & dosage*; D006624:Hippocampus / Q000187:drug effects* / Q000378:metabolism / Q000473:pathology; D002546:Ischemic Attack, Transient / Q000188:drug therapy* / Q000378:metabolism / Q000473:pathology / Q000523:psychology; D008297:Male; D057567:Memory, Long-Term / Q000187:drug effects* / Q000502:physiology; D019636:Neurodegenerative Diseases / Q000188:drug therapy / Q000378:metabolism / Q000473:pathology / Q000523:psychology; D009473:Neuronal Plasticity / Q000187:drug effects / Q000502:physiology; D018696:Neuroprotective Agents / Q000008:administration & dosage*; D018697:Nootropic Agents / Q000008:administration & dosage; D017208:Rats, Wistar; D013997:Time Factors
chemical_list: D005395:Fish Oils; D018696:Neuroprotective Agents; D018697:Nootropic Agents; D004281:Docosahexaenoic Acids
keywords: Dendritic loss; Dendritic neuroplasticity; Fish oil; Global cerebral ischemia; Memory protection; Retrograde amnesia