Limits...
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.

Show MeSH

Related in: MedlinePlus

Gas chromatography mass spectrometry (GC/MS) analysis of cholesterol precursors 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 cholesterol precursors analysed using GC/MS. The data indicates the fold change in the levels of cholesterol precursors detected in the PD (black bars) samples relative to the Con (white bars) samples. Absolute values for the cholesterol precursors in the different brain regions are provided as Table S8. Squalene (Squa); lanosterol (Lano), 14-dimethyl lanosterol (14-DL), zymosterol (Zymo), desmosterol (Desmo), lathosterol (Latho), 7-dehyrocholesterol (7-DC). Data represent mean ± SEM.
© Copyright Policy
Related In: Results  -  Collection


getmorefigures.php?uid=PMC3046155&req=5

pone-0017299-g010: Gas chromatography mass spectrometry (GC/MS) analysis of cholesterol precursors 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 cholesterol precursors analysed using GC/MS. The data indicates the fold change in the levels of cholesterol precursors detected in the PD (black bars) samples relative to the Con (white bars) samples. Absolute values for the cholesterol precursors in the different brain regions are provided as Table S8. Squalene (Squa); lanosterol (Lano), 14-dimethyl lanosterol (14-DL), zymosterol (Zymo), desmosterol (Desmo), lathosterol (Latho), 7-dehyrocholesterol (7-DC). Data represent mean ± SEM.

Mentions: In order to understand if cholesterol synthesis or metabolism may be altered in the PD VC, a further investigation of cholesterol biosynthetic precursor molecules as well as a range of oxysterol metabolites, that are indicated by the scheme depicted in Figure 9, was carried out using GC/MS analysis of the full sample cohort. There were no significant increases in any of the seven cholesterol precursor molecules assessed in any of the brain regions (Fig. 10). Intriguingly, lathosterol and 7-dehydrocholesterol levels were significantly reduced in the PD ACC compared to the control ACC (Fig. 10). The significance of this finding is not clear since the cholesterol levels were not different in the PD ACC versus control ACC (Figs. 3 and 8). Lathosterol was the only cholesterol precursor found to be correlated with age. This correlation was weak and only observed in the ACC (r2 = −0.23, p = 0.031). Age did not appear to have a major impact on the magnitude of PD-related differences in ACC lathosterol 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 lathosterol levels were 24.1±2.4 ng/mg and 16.1±2.3 in the Con (n = 10) and PD (n = 10) groups, respectively (t-test p = 0.026); whereas in the age-matched cohort lathosterol levels were 23.6±2.8 ng/mg and 16.8±2.6 in the Con (n = 8) and PD (n = 8) groups, respectively (t-test p = 0.097).


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 cholesterol precursors 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 cholesterol precursors analysed using GC/MS. The data indicates the fold change in the levels of cholesterol precursors detected in the PD (black bars) samples relative to the Con (white bars) samples. Absolute values for the cholesterol precursors in the different brain regions are provided as Table S8. Squalene (Squa); lanosterol (Lano), 14-dimethyl lanosterol (14-DL), zymosterol (Zymo), desmosterol (Desmo), lathosterol (Latho), 7-dehyrocholesterol (7-DC). Data represent mean ± SEM.
© Copyright Policy
Related In: Results  -  Collection

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

pone-0017299-g010: Gas chromatography mass spectrometry (GC/MS) analysis of cholesterol precursors 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 cholesterol precursors analysed using GC/MS. The data indicates the fold change in the levels of cholesterol precursors detected in the PD (black bars) samples relative to the Con (white bars) samples. Absolute values for the cholesterol precursors in the different brain regions are provided as Table S8. Squalene (Squa); lanosterol (Lano), 14-dimethyl lanosterol (14-DL), zymosterol (Zymo), desmosterol (Desmo), lathosterol (Latho), 7-dehyrocholesterol (7-DC). Data represent mean ± SEM.
Mentions: In order to understand if cholesterol synthesis or metabolism may be altered in the PD VC, a further investigation of cholesterol biosynthetic precursor molecules as well as a range of oxysterol metabolites, that are indicated by the scheme depicted in Figure 9, was carried out using GC/MS analysis of the full sample cohort. There were no significant increases in any of the seven cholesterol precursor molecules assessed in any of the brain regions (Fig. 10). Intriguingly, lathosterol and 7-dehydrocholesterol levels were significantly reduced in the PD ACC compared to the control ACC (Fig. 10). The significance of this finding is not clear since the cholesterol levels were not different in the PD ACC versus control ACC (Figs. 3 and 8). Lathosterol was the only cholesterol precursor found to be correlated with age. This correlation was weak and only observed in the ACC (r2 = −0.23, p = 0.031). Age did not appear to have a major impact on the magnitude of PD-related differences in ACC lathosterol 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 lathosterol levels were 24.1±2.4 ng/mg and 16.1±2.3 in the Con (n = 10) and PD (n = 10) groups, respectively (t-test p = 0.026); whereas in the age-matched cohort lathosterol levels were 23.6±2.8 ng/mg and 16.8±2.6 in the Con (n = 8) and PD (n = 8) groups, respectively (t-test p = 0.097).

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