Phosphoinositide signaling in human brain

Pacheco, Mary A.; Jope, Richard S.

doi:10.1016/s0301-0082(96)00035-4

Cited by 74 publications

(39 citation statements)

References 60 publications

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“…Interestingly, according to recent data Rap1 seems to regulate or be regulated by several signal transduction pathways, including those linked to neurotropic factors, 16,47-55 most of which have been found altered in affective disorders. 4,6,30,[56][57][58][59][60][61] The current data, joined to our previous study, 20 suggest that dysfunctions of the cAMP signaling system are linked to both major depression and bipolar disorder. However, it is worth mentioning that the manner in which PKA and Rap1 are altered in both disorders is somewhat different, thus suggesting that bipolar and unipolar disorders may be associated with distinctive biochemical abnormalities of a common pathway.…”

Section: Discussionsupporting

confidence: 62%

Protein kinase A and Rap1 levels in platelets of untreated patients with major depression

et al. 2000

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We have recently reported altered levels of protein kinase A and Rap1 in patients with bipolar disorder. The purpose of the current investigation was to assess the levels of these proteins in platelets from untreated euthymic and depressed patients with major unipolar depression. Platelets were collected from 45 drug-free unipolar patients (13 euthymic and 32 depressed) and 45 healthy subjects. The levels of protein kinase A and Rap1 were assessed by Western blot analysis, immunostaining and computer-assisted imaging. The immunolabeling of the regulatory subunit type II of protein kinase A and that of Rap1 was significantly lower in untreated depressed patients compared with untreated euthymic patients and healthy subjects. No significant differences were found in the immunolabeling of both the regulatory type I and the catalytic subunits of protein kinase A among groups. Levels of the regulatory subunit type II of protein kinase A and Rap1 are altered in platelets of unipolar depressive patients. These findings may provide new insight about the relationship between components of cAMP signaling and affective disorders. Molecular Psychiatry (2001) 6, 44-49.

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Section: Discussionsupporting

confidence: 62%

Protein kinase A and Rap1 levels in platelets of untreated patients with major depression

et al. 2000

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“…Restoration of neuronal membrane stability could alter various processes to normalize neurotransmitter systems that may be involved in the pathophysiology of mood disorder (Carlezon et al, 2005;Nomura et al, 2001;Pacheco and Jope, 1996). CDP-choline exerts effects to increase cerebral dopamine and norepinephrine levels (Martinet et al, 1978(Martinet et al, , 1979Agut et al, 1984;Saligaut et al, 1985).…”

Section: Discussionmentioning

confidence: 99%

“…Biochemical alterations in the structure and function of neuronal membranes can affect the intracellular and extracellular processes and synaptic neurotransmission, all of which may be involved in the pathophysiology of mood disorders (Carlezon et al, 2005;Lands, 1992;Nomura et al, 2001;Pacheco and Jope, 1996). Pyrimidines have also shown antidepressant-like effects in animal studies (Carlezon et al, 2002(Carlezon et al, , 2005, which may stem from the alteration of cerebral neurotransmission (Carlezon et al, 2002;Martinet et al, 1978Martinet et al, , 1979.…”

Section: Introductionmentioning

confidence: 99%

Decreased Glutamate/Glutamine Levels May Mediate Cytidine’s Efficacy in Treating Bipolar Depression: A Longitudinal Proton Magnetic Resonance Spectroscopy Study

Yoon

Lyoo

Haws

et al. 2009

Neuropsychopharmacol

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Targeting the glutamatergic system has been suggested as a promising new option for developing treatment strategies for bipolar depression. Cytidine, a pyrimidine, may exert therapeutic effects through a pathway that leads to altered neuronal-glial glutamate cycling. Pyrimidines are also known to exert beneficial effects on cerebral phospholipid metabolism, catecholamine synthesis, and mitochondrial function, which have each been linked to the pathophysiology of bipolar depression. This study was aimed at determining cytidine's efficacy in bipolar depression and at assessing the longitudinal effects of cytidine on cerebral glutamate/glutamine levels. Thirty-five patients with bipolar depression were randomly assigned to receive the mood-stabilizing drug valproate plus either cytidine or placebo for 12 weeks. Midfrontal cerebral glutamate/glutamine levels were measured using proton magnetic resonance spectroscopy before and after 2, 4, and 12 weeks of oral cytidine administration. Cytidine supplementation was associated with an earlier improvement in depressive symptoms (weeks 1-4; p ¼ 0.02, 0.001, 0.002, and 0.004, respectively) and also produced a greater reduction in cerebral glutamate/glutamine levels in patients with bipolar depression (weeks 2, 4, and 12; p ¼ 0.004, 0.004, and 0.02, respectively). Cytidinerelated glutamate/glutamine decrements correlated with a reduction in depressive symptoms (p ¼ 0.001). In contrast, these relationships were not observed in the placebo add-on group. The study results suggest that cytidine supplementation of valproate is associated with an earlier treatment response in bipolar depression. Furthermore, cytidine's efficacy in bipolar depression may be mediated by decreased levels of cerebral glutamate and/or glutamine, consistent with alterations in excitatory neurotransmission.

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“…Phospholipase C-b1 (PLC-b1), a phosphodiesterase, has been shown to be important in postnatal-cortical development and plasticity [3][4][5] and is known to regulate key G protein-coupled signaling pathways in the human cortex. 6 Significantly, a recent microarray study has shown decreased levels of PLCb1 in the dorsolateral prefrontal cortex of subjects with schizophrenia (personal communication; Elizabeth Thomas), suggesting that expression of this important signaling protein may be altered in the cortex of subjects with this disorder.…”

Section: Introductionmentioning

confidence: 99%

Phospholipase C-β1 knockout mice exhibit endophenotypes modeling schizophrenia which are rescued by environmental enrichment and clozapine administration

et al. 2007

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Phospholipase C-b1 (PLC-b1) is a rate-limiting enzyme implicated in postnatal-cortical development and neuronal plasticity. PLC-b1 transduces intracellular signals from specific muscarinic, glutamate and serotonin receptors, all of which have been implicated in the pathogenesis of schizophrenia. Here, we present data to show that PLC-b1 knockout mice display locomotor hyperactivity, sensorimotor gating deficits as well as cognitive impairment. These changes in behavior are regarded as endophenotypes homologous to schizophrenialike symptoms in rodents. Importantly, the locomotor hyperactivity and sensorimotor gating deficits in PLC-b1 knockout mice are subject to beneficial modulation by environmental enrichment. Furthermore, clozapine but not haloperidol (atypical and typical antipsychotics, respectively) rescues the sensorimotor gating deficit in these animals, suggesting selective predictive validity. We also demonstrate a relationship between the beneficial effects of environmental enrichment and levels of M1/M4 muscarinic acetylcholine receptor binding in the neocortex and hippocampus. Thus we have demonstrated a novel mouse model, displaying disruption of multiple postsynaptic signals implicated in the pathogenesis of schizophrenia, a relevant behavioral phenotype and associated gene-environment interactions.

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Phosphoinositide signaling in human brain

Cited by 74 publications

References 60 publications

Protein kinase A and Rap1 levels in platelets of untreated patients with major depression

Protein kinase A and Rap1 levels in platelets of untreated patients with major depression

Decreased Glutamate/Glutamine Levels May Mediate Cytidine’s Efficacy in Treating Bipolar Depression: A Longitudinal Proton Magnetic Resonance Spectroscopy Study

Phospholipase C-β1 knockout mice exhibit endophenotypes modeling schizophrenia which are rescued by environmental enrichment and clozapine administration

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