Reductions in neuronal peroxisomes in multiple sclerosis grey matter.
BACKGROUND
Peroxisomes are organelles in eukaryotic cells with multiple functions including the detoxification of reactive oxygen species, plasmalogen synthesis and β-oxidation of fatty acids. Recent evidence has implicated peroxisomal dysfunction in models of multiple sclerosis (MS) disease progression.


OBJECTIVE
Our aims were to determine whether there are changes in peroxisomes in MS grey matter (GM) compared to control GM.


METHODS
We analysed cases of MS and control GM immunocytochemically to assess peroxisomal membrane protein (PMP70) and neuronal proteins. We examined the expression of ABCD3 (the gene that encodes PMP70) in MS and control GM. Analyses of very long chain fatty acid (VLCFA) levels in GM were performed.


RESULTS
PMP70 immunolabelling of neuronal somata was significantly lower in MS GM compared to control. Calibration of ABCD3 gene expression with reference to glyceraldehyde 3-phsophate dehydrogenase (GAPDH) revealed overall decreases in expression in MS compared to controls. Mean PMP70 counts in involved MS GM negatively correlated to disease duration. Elevations in C26:0 (hexacosanoic acid) were found in MS GM.


CONCLUSIONS
Collectively, these observations provide evidence that there is an overall reduction in peroxisomal gene expression and peroxisomal proteins in GM neurons in MS. Changes in peroxisomal function may contribute to neuronal dysfunction and degeneration in MS.
MS and Stem Cell Labs, University of Bristol, UK.
Elizabeth
E
Gray
Claire
C
Rice
Kelly
K
Hares
Juliana
J
Redondo
Kevin
K
Kemp
Marcus
M
Williams
Ann
A
Brown
Neil
N
Scolding
Alastair
A
Wilkins
D018528:ATP-Binding Cassette Transporters / Q000378:metabolism; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D005260:Female; D015870:Gene Expression / Q000502:physiology; D066128:Gray Matter / Q000378:metabolism / Q000473:pathology*; D006801:Humans; D008297:Male; D008565:Membrane Proteins / Q000378:metabolism*; D008875:Middle Aged; D009103:Multiple Sclerosis / Q000473:pathology*; D009474:Neurons / Q000378:metabolism / Q000473:pathology*; D020675:Peroxisomes / Q000473:pathology*
C063305:ABCD3 protein, human; D018528:ATP-Binding Cassette Transporters; D008565:Membrane Proteins
Peroxisomes; grey matter; multiple sclerosis