Modification of brain lipids but not phenotype in alpha-synucleinopathy transgenic mice by long-term dietary n-3 fatty acids.
Transgenic mice expressing both wild mouse alpha-synuclein and the Parkinson's disease associated A53T mutated human alpha-synuclein were subjected to long-term diets impoverished in n-3 or diets impoverished in n-3 and supplemented with docosahexaenoic acid (DHA) for 6 months. Transgenic mice evidenced mild phenotype characterized by increased total alpha-synuclein expression, truncated alpha-synuclein forms, and abnormal solubility and aggregation, in the absence of Lewy bodies and neurites, and lack of apparent neuronal loss, astrocytosis and microgliosis. These diets produced a reduction in the content of linolenic, n-3 docosapentaenoic and total polyunsaturated fatty acids, leading to significantly lower double bond and peroxidizability indexes as well as to lower protein oxidative damage, with no effects in alpha-synuclein expression and with no modifications in the number of cortical astrocytes and microglial cells. The present results show that diets may modify brain lipid composition and susceptibility to oxidative damage that do not interfere with phenotype in models with a genetic susceptibility to develop alpha-synucleinopathy.
Muntané
Gerard
G
Institut de Neuropatologia, Servei Anatomia Patològica, IDIBELL-Hospital Universitari de Bellvitge, Hospitalet de Llobregat, CIBERNED, Barcelona, Spain.
Janué
Anna
A
Fernandez
Nuria
N
Odena
Maria Antonia
MA
Oliveira
Eliandre
E
Boluda
Susana
S
Portero-Otin
Manuel
M
Naudí
Alba
A
Boada
Jordi
J
Pamplona
Reinald
R
Ferrer
Isidre
I
D000818:Animals; D015153:Blotting, Western; D001921:Brain / Q000187:drug effects* / Q000378:metabolism; D004041:Dietary Fats / Q000008:administration & dosage*; D004591:Electrophoresis, Polyacrylamide Gel; D015525:Fatty Acids, Omega-3 / Q000008:administration & dosage*; D007150:Immunohistochemistry; D050356:Lipid Metabolism; D013058:Mass Spectrometry; D051379:Mice; D008970:Molecular Weight; D018384:Oxidative Stress; D010641:Phenotype; D020133:Reverse Transcriptase Polymerase Chain Reaction; D051844:alpha-Synuclein / Q000378:metabolism*
D004041:Dietary Fats; D015525:Fatty Acids, Omega-3; D051844:alpha-Synuclein