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Lipid pathway alterations in Parkinson's disease primary visual cortex.

Cheng D, Jenner AM, Shui G, Cheong WF, Mitchell TW, Nealon JR, Kim WS, McCann H, Wenk MR, Halliday GM, Garner B - PLoS ONE (2011)

Bottom Line: We have focused on the primary visual cortex, a region that is devoid of pathological changes and Lewy bodies; and two additional regions, the amygdala and anterior cingulate cortex which contain Lewy bodies at different disease stages but do not have as severe degeneration as the substantia nigra.False discovery rate analysis confirmed that 73 of these 79 lipid species were significantly changed in the visual cortex (q-value <0.05).Many of these changes in visual cortex lipids were correlated with relevant changes in the expression of genes involved in lipid metabolism and an oxidative stress response as determined by quantitative polymerase chain reaction techniques.

View Article: PubMed Central - PubMed

Affiliation: Neuroscience Research Australia, Sydney, New South Wales, Australia.

ABSTRACT

Background: We present a lipidomics analysis of human Parkinson's disease tissues. We have focused on the primary visual cortex, a region that is devoid of pathological changes and Lewy bodies; and two additional regions, the amygdala and anterior cingulate cortex which contain Lewy bodies at different disease stages but do not have as severe degeneration as the substantia nigra.

Methodology/principal findings: Using liquid chromatography mass spectrometry lipidomics techniques for an initial screen of 200 lipid species, significant changes in 79 sphingolipid, glycerophospholipid and cholesterol species were detected in the visual cortex of Parkinson's disease patients (n = 10) compared to controls (n = 10) as assessed by two-sided unpaired t-test (p-value <0.05). False discovery rate analysis confirmed that 73 of these 79 lipid species were significantly changed in the visual cortex (q-value <0.05). By contrast, changes in 17 and 12 lipid species were identified in the Parkinson's disease amygdala and anterior cingulate cortex, respectively, compared to controls; none of which remained significant after false discovery rate analysis. Using gas chromatography mass spectrometry techniques, 6 out of 7 oxysterols analysed from both non-enzymatic and enzymatic pathways were also selectively increased in the Parkinson's disease visual cortex. Many of these changes in visual cortex lipids were correlated with relevant changes in the expression of genes involved in lipid metabolism and an oxidative stress response as determined by quantitative polymerase chain reaction techniques.

Conclusions/significance: The data indicate that changes in lipid metabolism occur in the Parkinson's disease visual cortex in the absence of obvious pathology. This suggests that normalization of lipid metabolism and/or oxidative stress status in the visual cortex may represent a novel route for treatment of non-motor symptoms, such as visual hallucinations, that are experienced by a majority of Parkinson's disease patients.

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Related in: MedlinePlus

Gas chromatography mass spectrometry (GC/MS) analysis of oxysterols in the anterior cingulate cortex (ACC), amygdala (AMY) and visual cortex (VC) of control (Con) and Parkinson's disease (PD) tissues.Control (n = 10) and PD (n = 10) tissues were collected from the ACC (A), AMY (B) and VC (C). Lipids were extracted and oxysterols analysed using GC/MS. The data indicates the fold change in the levels of oxysterols detected in the PD (black bars) samples relative to the Con (white bars) samples. 7α-hydroxycholesterol (7αOHC); 7β-hydroxycholesterol (7βOHC); cholesterol-5α,6α-epoxide (5,6αEC); cholesterol-5β,6β-epoxide (5,6βEC); 7keto-cholesterol (7KC); 27-hydroxycholesterol (27OHC); 24-hydroxycholesterol (24OHC). Data represent mean ± SEM, *p<0.05, **p<0.001 by t-test.
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pone-0017299-g011: Gas chromatography mass spectrometry (GC/MS) analysis of oxysterols in the anterior cingulate cortex (ACC), amygdala (AMY) and visual cortex (VC) of control (Con) and Parkinson's disease (PD) tissues.Control (n = 10) and PD (n = 10) tissues were collected from the ACC (A), AMY (B) and VC (C). Lipids were extracted and oxysterols analysed using GC/MS. The data indicates the fold change in the levels of oxysterols detected in the PD (black bars) samples relative to the Con (white bars) samples. 7α-hydroxycholesterol (7αOHC); 7β-hydroxycholesterol (7βOHC); cholesterol-5α,6α-epoxide (5,6αEC); cholesterol-5β,6β-epoxide (5,6βEC); 7keto-cholesterol (7KC); 27-hydroxycholesterol (27OHC); 24-hydroxycholesterol (24OHC). Data represent mean ± SEM, *p<0.05, **p<0.001 by t-test.

Mentions: The GC/MS analysis revealed a significant increase in PD VC oxysterols derived from both enzymatic and non-enzymatic routes (Fig. 11). Of the seven oxysterols analysed, 5,6α-epoxy-Ch was the only compound that was not significantly increased (although there was a trend for an increase) in the PD VC (Fig. 11). 7Keto-Ch was the only oxysterol found to be correlated with age. This correlation was weak and only observed in the VC (r2 = 0.20, p = 0.049). Similar to the observations regarding lathosterol above, age did not have an impact on the magnitude of PD-related differences in VC 7keto-Ch levels we detected in the full sample cohort as very similar data were generated using the age-matched samples (i.e. in the full cohort 7keto-Ch levels were 2.74±0.40 ng/mg and 4.73±0.40 in the Con (n = 10) and PD (n = 10) groups, respectively (t-test p = 0.002); whereas in the age-matched cohort 7keto-Ch levels were 2.83±0.49 ng/mg and 4.86±0.49 in the Con (n = 8) and PD (n = 8) groups, respectively (t-test p = 0.011).


Lipid pathway alterations in Parkinson's disease primary visual cortex.

Cheng D, Jenner AM, Shui G, Cheong WF, Mitchell TW, Nealon JR, Kim WS, McCann H, Wenk MR, Halliday GM, Garner B - PLoS ONE (2011)

Gas chromatography mass spectrometry (GC/MS) analysis of oxysterols in the anterior cingulate cortex (ACC), amygdala (AMY) and visual cortex (VC) of control (Con) and Parkinson's disease (PD) tissues.Control (n = 10) and PD (n = 10) tissues were collected from the ACC (A), AMY (B) and VC (C). Lipids were extracted and oxysterols analysed using GC/MS. The data indicates the fold change in the levels of oxysterols detected in the PD (black bars) samples relative to the Con (white bars) samples. 7α-hydroxycholesterol (7αOHC); 7β-hydroxycholesterol (7βOHC); cholesterol-5α,6α-epoxide (5,6αEC); cholesterol-5β,6β-epoxide (5,6βEC); 7keto-cholesterol (7KC); 27-hydroxycholesterol (27OHC); 24-hydroxycholesterol (24OHC). Data represent mean ± SEM, *p<0.05, **p<0.001 by t-test.
© Copyright Policy
Related In: Results  -  Collection

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getmorefigures.php?uid=PMC3046155&req=5

pone-0017299-g011: Gas chromatography mass spectrometry (GC/MS) analysis of oxysterols in the anterior cingulate cortex (ACC), amygdala (AMY) and visual cortex (VC) of control (Con) and Parkinson's disease (PD) tissues.Control (n = 10) and PD (n = 10) tissues were collected from the ACC (A), AMY (B) and VC (C). Lipids were extracted and oxysterols analysed using GC/MS. The data indicates the fold change in the levels of oxysterols detected in the PD (black bars) samples relative to the Con (white bars) samples. 7α-hydroxycholesterol (7αOHC); 7β-hydroxycholesterol (7βOHC); cholesterol-5α,6α-epoxide (5,6αEC); cholesterol-5β,6β-epoxide (5,6βEC); 7keto-cholesterol (7KC); 27-hydroxycholesterol (27OHC); 24-hydroxycholesterol (24OHC). Data represent mean ± SEM, *p<0.05, **p<0.001 by t-test.
Mentions: The GC/MS analysis revealed a significant increase in PD VC oxysterols derived from both enzymatic and non-enzymatic routes (Fig. 11). Of the seven oxysterols analysed, 5,6α-epoxy-Ch was the only compound that was not significantly increased (although there was a trend for an increase) in the PD VC (Fig. 11). 7Keto-Ch was the only oxysterol found to be correlated with age. This correlation was weak and only observed in the VC (r2 = 0.20, p = 0.049). Similar to the observations regarding lathosterol above, age did not have an impact on the magnitude of PD-related differences in VC 7keto-Ch levels we detected in the full sample cohort as very similar data were generated using the age-matched samples (i.e. in the full cohort 7keto-Ch levels were 2.74±0.40 ng/mg and 4.73±0.40 in the Con (n = 10) and PD (n = 10) groups, respectively (t-test p = 0.002); whereas in the age-matched cohort 7keto-Ch levels were 2.83±0.49 ng/mg and 4.86±0.49 in the Con (n = 8) and PD (n = 8) groups, respectively (t-test p = 0.011).

Bottom Line: We have focused on the primary visual cortex, a region that is devoid of pathological changes and Lewy bodies; and two additional regions, the amygdala and anterior cingulate cortex which contain Lewy bodies at different disease stages but do not have as severe degeneration as the substantia nigra.False discovery rate analysis confirmed that 73 of these 79 lipid species were significantly changed in the visual cortex (q-value <0.05).Many of these changes in visual cortex lipids were correlated with relevant changes in the expression of genes involved in lipid metabolism and an oxidative stress response as determined by quantitative polymerase chain reaction techniques.

View Article: PubMed Central - PubMed

Affiliation: Neuroscience Research Australia, Sydney, New South Wales, Australia.

ABSTRACT

Background: We present a lipidomics analysis of human Parkinson's disease tissues. We have focused on the primary visual cortex, a region that is devoid of pathological changes and Lewy bodies; and two additional regions, the amygdala and anterior cingulate cortex which contain Lewy bodies at different disease stages but do not have as severe degeneration as the substantia nigra.

Methodology/principal findings: Using liquid chromatography mass spectrometry lipidomics techniques for an initial screen of 200 lipid species, significant changes in 79 sphingolipid, glycerophospholipid and cholesterol species were detected in the visual cortex of Parkinson's disease patients (n = 10) compared to controls (n = 10) as assessed by two-sided unpaired t-test (p-value <0.05). False discovery rate analysis confirmed that 73 of these 79 lipid species were significantly changed in the visual cortex (q-value <0.05). By contrast, changes in 17 and 12 lipid species were identified in the Parkinson's disease amygdala and anterior cingulate cortex, respectively, compared to controls; none of which remained significant after false discovery rate analysis. Using gas chromatography mass spectrometry techniques, 6 out of 7 oxysterols analysed from both non-enzymatic and enzymatic pathways were also selectively increased in the Parkinson's disease visual cortex. Many of these changes in visual cortex lipids were correlated with relevant changes in the expression of genes involved in lipid metabolism and an oxidative stress response as determined by quantitative polymerase chain reaction techniques.

Conclusions/significance: The data indicate that changes in lipid metabolism occur in the Parkinson's disease visual cortex in the absence of obvious pathology. This suggests that normalization of lipid metabolism and/or oxidative stress status in the visual cortex may represent a novel route for treatment of non-motor symptoms, such as visual hallucinations, that are experienced by a majority of Parkinson's disease patients.

Show MeSH
Related in: MedlinePlus