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Articles, Neurobiology of Disease

Postmortem Brain Tissue of Depressed Suicides Reveals Increased Gsα Localization in Lipid Raft Domains Where It Is Less Likely to Activate Adenylyl Cyclase

Robert J. Donati, Yogesh Dwivedi, Rosalinda C. Roberts, Robert R. Conley, Ghanshyam N. Pandey and Mark M. Rasenick
Journal of Neuroscience 19 March 2008, 28 (12) 3042-3050; https://doi.org/10.1523/JNEUROSCI.5713-07.2008
Robert J. Donati
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Yogesh Dwivedi
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Rosalinda C. Roberts
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Robert R. Conley
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Ghanshyam N. Pandey
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Mark M. Rasenick
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    Figure 1.

    Representative SDS-PAGE gel autoradiograms for cerebellum and prefrontal cortex samples. A, Representative Gsα immunoblots of TX-100 and TX-114 extracts from cerebellum membranes of control (C) and depressed suicide (S) subjects. B, Representative Gsα immunoblots of TX-100 and TX-114 extracts from prefrontal cortex membranes of control and depressed suicide subjects. Gsα bands are indicated by arrows.

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    Figure 2.

    Comparison of the total extractable Gsα in both the cerebellum and prefrontal cortex of depressed and control subjects. Graphic representation of the normalized densitometric values of TX-100-soluble (100) and TX-100-resistant (114) Gsα from both cerebellum and prefrontal cortex. A, Data were acquired from densitometric determinations of gels and autoradiographs on cerebellum samples. Control versus suicide TX-100-soluble (100) and control versus suicide TX-100-resistant (114) Gsα were examined. A one-way ANOVA followed by a Newman–Keuls multiple-comparison test was performed and the means were not found to be significantly different (p > 0.05). There was no significant difference in the total amount (TX-100 plus TX-114) of extractable Gsα (n = 14 for control and n = 13 for suicide subjects). B, Data were acquired from densitometric determinations of gels and autoradiographs from prefrontal cortex samples. Control versus suicide TX-100-soluble (100) and control versus suicide TX-100-resistant (114) Gsα were examined. A one-way ANOVA followed by a Newman–Keuls multiple-comparison test was performed, and the means were found to be significantly different. ***p < 0.001, control versus suicide TX-100. *p < 0.05, control versus suicide TX-114. There was a significant difference in the total amount (TX-100 plus TX-114) of extractable Gsα in control versus suicide subjects, p < 0.0003 (n = 14 for control and n = 14 for suicide subjects), in the prefrontal cortex, but not in the cerebellum. Error bars indicate SEM.

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    Figure 3.

    Depressed subjects have significantly more raft-associated Gsα in the cerebellum and prefrontal cortex compared with control subjects. Graphic representation of the normalized densitometric ratios of TX-100-soluble and TX-100-resistant Gsα (TX-100/TX-114). A, Data were acquired from gels and autoradiographs on cerebellum samples. An unpaired t test was performed and the means were found to be significantly different, p < 0.02 (n = 14 for control and n = 13 for suicide subjects). B, Data were acquired from gels and autoradiographs from prefrontal cortex samples, and the average of those ratios is presented. An unpaired t test was performed, and the means were found to be significantly different, p < 0.05 (n = 14 for control and n = 15 for suicide subjects).

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    Figure 4.

    The membrane localization of Gqα in depressed subjects is unaltered in the prefrontal cortex and cerebellum compared with control subjects. Graphic representation of the normalized densitometric ratios of TX-100-soluble (100) and TX-100-resistant (114) Gqα from a small pool of prefrontal cortex (cx) and cerebellum (cb) samples. Data were acquired from gels and autoradiographs of cerebral cortex and cerebellum samples (some of which involved stripping and reprobing of blots used for Gsα determination). Samples were probed for Gqα. A one-way ANOVA was performed, and no significant differences were found (n = 4 for control and n = 4 for suicide subjects). Error bars indicate SEM.

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    Table 1.

    Demographic characteristics of suicide and control subjects

    Age (years)RaceGenderPMI (h)Cause of deathDrug screen(at the time of death)Psychiatric diagnosis
    1Control22BlackMale19GSWNoneNormal
    2Control37BlackMale5ASCVDNoneNormal
    3Control31BlackMale8GSWLidocaineNormal
    4Control46BlackMale9Multiple injuriesNoneNormal
    5Control33WhiteMale15GSWAcetaminophenNormal
    6Control48WhiteMale26ASCVDNoneNormal
    7Control40WhiteFemale7ASCVDNoneNormal
    8Control23BlackMale15GSWNoneNormal
    9Control38BlackMale16Lung sarcoidosisNoneNormal
    10Control83WhiteMale20ASCVDNoneNormal
    11Control65BlackFemale23ASCVDNoneNormal
    12Control35WhiteMale24Crush injury to abdomen and chestNoneNormal
    13Control52WhiteMale30ASCVDNoneNormal
    14Control63WhiteFemale30Ovarian cancerNoneNormal
    15Control37WhiteMale24ASCVDNoneNormal
    16Control45WhiteMale22ASCVDNoneNormal
    1Suicide26BlackMaleNAHangingCocaineNA
    2Suicide21BlackMale4HangingCocaine, morphineOpiate abuse, cocaine abuse
    3Suicide50WhiteMale7GSWNoneNo psychiatric illness
    4Suicide27WhiteMale24GSWNoneMajor depression, alcohol abuse
    5Suicide24WhiteMale7GSWEthanolMajor depression
    6Suicide21WhiteMale17GSWNoneAdjustment disorder with mixed disturbance of emotions and conduct
    7Suicide75WhiteMale18GSWNoneAdjustment disorder/conduct disorder
    8Suicide41BlackMale12JumpingsuicideNoneNot enough information
    9Suicide41WhiteFemale27Drug overdoseAmitriptyline, desipramine, diphenhydramine, nortriptyline, pseudophedrine, salicylate, ethanolMajor depression, alcohol abuse
    10Suicide68WhiteFemale26GSWAmitriptylineBipolar disorder
    11Suicide22BlackFemale16Drug overdosePropranololMajor depression
    12Suicide39WhiteMale30AsphyxiaFreon, cocaine, and metabolitesCocaine abuse
    13Suicide30WhiteMale32HangingCocaine, ethanolAlcohol abuse, cocaine abuse, drug abuse
    14Suicide46WhiteFemale21Drug overdoseAmitriptyline, desipramine, ranitidine, ethanolMajor depression
    15Suicide20WhiteMale32HangingEthanolAlcohol abuse
    16Suicide21WhiteMale23HangingNoneAdjustment disorder conduct
    • ASCVD, Atherosclerotic cardiovascular disease; GSW, gunshot wound; NA, not available.

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    Table 2.

    Summary of results

    CerebellumPFC
    Total extractable GsNS↓ Suicide
    TX-100 soluble (TX-100)NS↓ Suicide
    TX-100 resistant (TX-114)NS↓ Suicide
    ANCOVA (PMI, pH, age) TX-100—No effect
    ANCOVA (PMI, pH, age) TX-114—No effect
    ANCOVA (AD) TX-100No effectNo effect
    ANCOVA (AD) TX-114No effectNo effect
    ANCOVA (drug) TX-100—No effect
    ANCOVA (drug) TX-114—No effect
    TX-100/TX-114 Ratio↓ Suicide↓ Suicide
    ANCOVA (PMI, pH, age) TX-100/TX-114No effectNo effect
    ANCOVA (AD) TX-100/TX-114No effectNo effect
    ANCOVA (drug) TX-100/TX-114No effectNo effect
    • NS, No significant difference between control and suicide subjects; ↓Suicide, significant decrease in the suicide subjects compared with control; —, not measured; ANCOVA, analysis of confounding variables (in parentheses) was used when there was a significant difference between values measured and when antidepressants were found in the subjects at the time of death; no effect, analysis of the data with the confounding variable had no effect on the original analysis.

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The Journal of Neuroscience: 28 (12)
Journal of Neuroscience
Vol. 28, Issue 12
19 Mar 2008
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Postmortem Brain Tissue of Depressed Suicides Reveals Increased Gsα Localization in Lipid Raft Domains Where It Is Less Likely to Activate Adenylyl Cyclase
Robert J. Donati, Yogesh Dwivedi, Rosalinda C. Roberts, Robert R. Conley, Ghanshyam N. Pandey, Mark M. Rasenick
Journal of Neuroscience 19 March 2008, 28 (12) 3042-3050; DOI: 10.1523/JNEUROSCI.5713-07.2008

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Postmortem Brain Tissue of Depressed Suicides Reveals Increased Gsα Localization in Lipid Raft Domains Where It Is Less Likely to Activate Adenylyl Cyclase
Robert J. Donati, Yogesh Dwivedi, Rosalinda C. Roberts, Robert R. Conley, Ghanshyam N. Pandey, Mark M. Rasenick
Journal of Neuroscience 19 March 2008, 28 (12) 3042-3050; DOI: 10.1523/JNEUROSCI.5713-07.2008
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