Frontal lobe gray matter density decreases in bipolar I disorder

Lyoo, In Kyoon; Kim, M. Justin; Stoll, Andrew L.; Demopulos, Christina M.; Parow, Aimee; Dager, Stephen R.; Friedman, Seth D.; Dünner, David L.; Renshaw, Perry F.

doi:10.1016/j.biopsych.2003.10.017

Cited by 248 publications

(194 citation statements)

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“…Since cPLA 2 can be phosphorylated and activated by PKC, we also determined protein levels of PKC a and PKC e as well as AA-dependent PKC activity, in frontal cortex of control and lithium-treated rats. We studied the frontal cortex because of evidence of decreased gray matter volume, and reduced neuronal and glial densities, in the frontal cortex of bipolar disorder patients (Lopez-Larson et al, 2002;Lyoo et al, 2004;Rajkowska, 2002).…”

Section: Introductionmentioning

confidence: 99%

Decrease in the AP-2 DNA-Binding Activity and in the Protein Expression of AP-2 α and AP-2 β in Frontal Cortex of Rats Treated with Lithium for 6 Weeks

Rao

Rapoport

Bosetti

2005

Neuropsychopharmacol

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Lithium chloride (LiCl), when fed to rats for 6 weeks, has been reported to decrease brain mRNA, protein, and activity levels of arachidonic acid (AA)-selective cytosolic phospholipase A 2 (cPLA 2 ), without affecting secretory sPLA 2 or Ca 2 þ -independent iPLA 2 . We investigated whether transcription factors known to regulate cPLA 2 gene expression are modulated by chronic lithium treatment. Male Fischer-344 rats were fed a LiCl-containing diet for 6 weeks to produce a therapeutically relevant brain lithium concentration. Control animals were fed a LiCl-free diet. Using a gelshift assay, we found that LiCl significantly decreased activating protein 2 (AP-2)-binding activity, and protein levels of the AP-2 a and AP-2 b but not of the AP-2 g subunits in the frontal cortex. Activating protein 1 (AP-1)-binding activity was increased, whereas glucocorticoid response element, polyoma enhancer activator 3, and nuclear factor kappa B DNA-binding activities were not changed significantly. Since both cPLA 2 and AP-2 can be activated by protein kinase C (PKC), we examined the frontal cortex protein levels of PKC a and PKC e, as well as AA-dependent PKC activity. The protein levels of PKC a and PKC e were decreased significantly, as was AA-dependent PKC activity, in the lithium-treated compared to control rats. Our results suggest that the reported decrease in brain gene expression of cPLA 2 by chronic lithium may be mediated by reduced AP-2 transcriptional activity, and that decreased expression of PKC a and PKC e contributes to lowering the AP-2 activity.

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Section: Introductionmentioning

confidence: 99%

Decrease in the AP-2 DNA-Binding Activity and in the Protein Expression of AP-2 α and AP-2 β in Frontal Cortex of Rats Treated with Lithium for 6 Weeks

Rao

Rapoport

Bosetti

2005

Neuropsychopharmacol

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“…44 Additionally, post-mortem investigations have shown decreased gray matter volume, lower DHA concentrations, and reduced neuronal and glial densities in the frontal cortex of bipolar disorder patients. 12,[45][46][47] Upon finding that BDNF, phosphorylated CREB and p38 MAPK were decreased in the rat frontal cortex after 15 weeks of dietary n-3 PUFA deprivation, we used rat primary cortical astrocytes to show that DHA induction of BDNF was blocked by a p38 MAPK inhibitor.…”

Section: Introductionmentioning

confidence: 99%

n-3 Polyunsaturated fatty acid deprivation in rats decreases frontal cortex BDNF via a p38 MAPK-dependent mechanism

et al. 2006

Mol Psychiatry

258

151

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Decreased docosahexaenoic acid (DHA) and brain-derived neurotrophic factor (BDNF) have been implicated in bipolar disorder. It also has been reported that dietary deprivation of n-3 polyunsaturated fatty acids (PUFAs) for 15 weeks in rats, increased their depression and aggression scores. Here, we show that n-3 PUFA deprivation for 15 weeks decreased the frontal cortex DHA level and reduced frontal cortex BDNF expression, cAMP response element binding protein (CREB) transcription factor activity and p38 mitogen-activated protein kinase (MAPK) activity. Activities of other CREB activating protein kinases were not significantly changed. The addition of DHA to rat primary cortical astrocytes in vitro, induced BDNF protein expression and this was blocked by a p38 MAPK inhibitor. DHA's ability to regulate BDNF via a p38 MAPK-dependent mechanism may contribute to its therapeutic efficacy in brain diseases having disordered cell survival and neuroplasticity.

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“…The etiology of this lack of functional activation remains unknown. Reduced gray matter in the IFC has been reported in several studies (Lopez-Larson et al, 2002;Lyoo et al, 2004;Foland-Ross et al, 2011), and reduced frontal gray matter density may provide an explanation for the functional abnormalities seen in patients with bipolar disorder across mood states. Alternatively, deficits in white matter tracts (Adler et al, 2004;Beyer et al, 2005) or white matter volume (Kieseppa et al, 2003) could also result in a disruption of normal activation in this frontal-striatal circuit.…”

Section: Discussionmentioning

confidence: 71%

Frontal lobe hypoactivation in medication-free adults with bipolar II depression during response inhibition

Penfold¹,

Vizueta²,

Townsend³

et al. 2015

Psychiatry Research: Neuroimaging

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Frontal lobe gray matter density decreases in bipolar I disorder

Cited by 248 publications

References 20 publications

Decrease in the AP-2 DNA-Binding Activity and in the Protein Expression of AP-2 α and AP-2 β in Frontal Cortex of Rats Treated with Lithium for 6 Weeks

Decrease in the AP-2 DNA-Binding Activity and in the Protein Expression of AP-2 α and AP-2 β in Frontal Cortex of Rats Treated with Lithium for 6 Weeks

n-3 Polyunsaturated fatty acid deprivation in rats decreases frontal cortex BDNF via a p38 MAPK-dependent mechanism

Frontal lobe hypoactivation in medication-free adults with bipolar II depression during response inhibition

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