PMID- 20336774
OWN - NLM
STAT- MEDLINE
DCOM- 20101026
LR  - 20211203
IS  - 1097-4547 (Electronic)
IS  - 0360-4012 (Linking)
VI  - 88
IP  - 10
DP  - 2010 Aug 1
TI  - Omega-3 fatty acids reverse age-related decreases in nuclear receptors and 
      increase neurogenesis in old rats.
PG  - 2091-102
LID - 10.1002/jnr.22390 [doi]
AB  - Retinoic acid receptors (RARs), retinoid X receptors (RXRs), and peroxisome 
      proliferator-activated receptors (PPARs) are transcription factors involved in 
      many cellular processes, such as learning and memory. RAR and RXR mRNA levels 
      decrease with ageing, and the decreases can be reversed by retinoic acid 
      treatment, which also alleviates age-related memory deficits. The omega-3 fatty 
      acids eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA) have 
      neuroprotective effects in the aged brain and are endogenous ligands of RXR and 
      PPAR. We investigated whether dietary EPA and DHA supplementation reverses 
      age-related declines in protein levels of these receptors in rat forebrain. Two 
      studies were conducted comparing adult and old rats. In the first, old rats were 
      fed standard or EPA/DHA-enriched (270 mg/kg/day, EPA to DHA ratio 1.5:1) diets 
      for 12 weeks. Analysis by Western blot revealed significant decreases in 
      RARalpha, RXRalpha, RXRbeta, and PPARgamma in the forebrain with ageing, which 
      were reversed by supplementation. Immunohistochemical analysis of the hippocampus 
      showed significant age-related decreases in RARalpha and RXRbeta expression in 
      CA1 and the dentate gyrus, which were restored by supplementation. Decreases in 
      hippocampal doublecortin expression were also partially alleviated, suggesting a 
      positive effect on neurogenesis. We also investigated the effects of DHA 
      supplementation (300 mg/kg/day for 12 weeks) on RARalpha, RXRalpha, and RXRbeta 
      expression in the prefrontal cortex, striatum, and hippocampus. Overall, DHA 
      supplementation appeared to increase receptor expression compared with the 
      untreated old group. These observations illustrate additional mechanisms that 
      might underlie the neuroprotective effects of omega-3 fatty acids in ageing.
FAU - Dyall, Simon C
AU  - Dyall SC
AD  - Neuroscience Centre, ICMS, St. Bartholomew's and the Royal London School of 
      Medicine and Dentistry, Queen Mary University of London, Whitechapel, London, 
      United Kingdom. sdyall@bcom.ac.uk
FAU - Michael, Gregory J
AU  - Michael GJ
FAU - Michael-Titus, Adina T
AU  - Michael-Titus AT
LA  - eng
PT  - Journal Article
PL  - United States
TA  - J Neurosci Res
JT  - Journal of neuroscience research
JID - 7600111
RN  - 0 (Dcx protein, rat)
RN  - 0 (Doublecortin Protein)
RN  - 0 (Fatty Acids, Omega-3)
RN  - 0 (Receptors, Cytoplasmic and Nuclear)
RN  - 25167-62-8 (Docosahexaenoic Acids)
RN  - AAN7QOV9EA (Eicosapentaenoic Acid)
SB  - IM
MH  - Aging/*physiology
MH  - Animals
MH  - Brain/*physiology
MH  - Diet
MH  - Dietary Supplements
MH  - Docosahexaenoic Acids/administration & dosage/metabolism
MH  - Doublecortin Protein
MH  - Eicosapentaenoic Acid/administration & dosage/metabolism
MH  - Fatty Acids, Omega-3/administration & dosage/*metabolism
MH  - Male
MH  - Neurogenesis/*physiology
MH  - Neurons/*physiology
MH  - Rats
MH  - Rats, Wistar
MH  - Receptors, Cytoplasmic and Nuclear/*metabolism
EDAT- 2010/03/26 06:00
MHDA- 2010/10/27 06:00
CRDT- 2010/03/26 06:00
PHST- 2010/03/26 06:00 [entrez]
PHST- 2010/03/26 06:00 [pubmed]
PHST- 2010/10/27 06:00 [medline]
AID - 10.1002/jnr.22390 [doi]
PST - ppublish
SO  - J Neurosci Res. 2010 Aug 1;88(10):2091-102. doi: 10.1002/jnr.22390.