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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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Analysis of control (Con) and Parkinson's disease (PD) α-synuclein (α-Syn) and synaptophysin (Sp) levels.Tissues were homogenised and fractionated as described in the legend to Figure 1 and insoluble α-Syn in the SDS fraction, and Sp in the TX-fraction was measured in the anterior cingulate cortex (ACC) (A), amygdala (AMY) (B), and visual cortex (VC) (C). Corresponding quantification of relative α-Syn (D) and Sp (E) protein expression in the three brain regions is provided in the histograms. Data represent mean ± SEM (n = 10), **p<0.001 by t-test.
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pone-0017299-g002: Analysis of control (Con) and Parkinson's disease (PD) α-synuclein (α-Syn) and synaptophysin (Sp) levels.Tissues were homogenised and fractionated as described in the legend to Figure 1 and insoluble α-Syn in the SDS fraction, and Sp in the TX-fraction was measured in the anterior cingulate cortex (ACC) (A), amygdala (AMY) (B), and visual cortex (VC) (C). Corresponding quantification of relative α-Syn (D) and Sp (E) protein expression in the three brain regions is provided in the histograms. Data represent mean ± SEM (n = 10), **p<0.001 by t-test.

Mentions: The amounts of α-syn in the SDS-soluble fractions were then used to estimate relative Lewy body pathology in all samples. The data indicate that α-syn deposition was significantly increased in the SDS-soluble fractions of the AMY of the PD cases as compared to the controls (Fig. 2). A non-significant trend for increased α-syn deposition in the ACC was also noted whereas there were no changes in the VC (Fig. 2). This is consistent with the Braak stages for these cases with ACC Lewy bodies (Braak PD stage V) found in 7/10 of the PD cases (Table 1). Synaptophysin levels were not altered in any of the samples analysed, suggesting that extensive neurodegeneration or synaptic loss was not a feature of the brain regions analysed in this PD cohort (Fig. 2).


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)

Analysis of control (Con) and Parkinson's disease (PD) α-synuclein (α-Syn) and synaptophysin (Sp) levels.Tissues were homogenised and fractionated as described in the legend to Figure 1 and insoluble α-Syn in the SDS fraction, and Sp in the TX-fraction was measured in the anterior cingulate cortex (ACC) (A), amygdala (AMY) (B), and visual cortex (VC) (C). Corresponding quantification of relative α-Syn (D) and Sp (E) protein expression in the three brain regions is provided in the histograms. Data represent mean ± SEM (n = 10), **p<0.001 by t-test.
© Copyright Policy
Related In: Results  -  Collection

Show All Figures
getmorefigures.php?uid=PMC3046155&req=5

pone-0017299-g002: Analysis of control (Con) and Parkinson's disease (PD) α-synuclein (α-Syn) and synaptophysin (Sp) levels.Tissues were homogenised and fractionated as described in the legend to Figure 1 and insoluble α-Syn in the SDS fraction, and Sp in the TX-fraction was measured in the anterior cingulate cortex (ACC) (A), amygdala (AMY) (B), and visual cortex (VC) (C). Corresponding quantification of relative α-Syn (D) and Sp (E) protein expression in the three brain regions is provided in the histograms. Data represent mean ± SEM (n = 10), **p<0.001 by t-test.
Mentions: The amounts of α-syn in the SDS-soluble fractions were then used to estimate relative Lewy body pathology in all samples. The data indicate that α-syn deposition was significantly increased in the SDS-soluble fractions of the AMY of the PD cases as compared to the controls (Fig. 2). A non-significant trend for increased α-syn deposition in the ACC was also noted whereas there were no changes in the VC (Fig. 2). This is consistent with the Braak stages for these cases with ACC Lewy bodies (Braak PD stage V) found in 7/10 of the PD cases (Table 1). Synaptophysin levels were not altered in any of the samples analysed, suggesting that extensive neurodegeneration or synaptic loss was not a feature of the brain regions analysed in this PD cohort (Fig. 2).

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