| 1 | Proc. Natl. Acad. Sci. U.S.A. 2001 Mar 98: 4066-71 |
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| PMID | 11274430 |
| Title | Increased CNS levels of apolipoprotein D in schizophrenic and bipolar subjects: implications for the pathophysiology of psychiatric disorders. |
| Abstract | Chronic administration of the atypical antipsychotic drug, clozapine, to rodents has been shown to increase the concentration of apolipoprotein D (APOD) in several area of the brain, suggesting that APOD could be involved in the therapeutic effects of antipsychotic drugs and/or the pathology of psychotic illnesses. Here, we measured a significant decrease in the concentration of APOD in serum samples from schizophrenic patients. In contrast, APOD levels were significantly increased (92--287%) in dorsolateral prefrontal cortex (Brodmann's area 9) of schizophrenic and bipolar subjects. Elevated levels of APOD expression were also observed in the caudate of schizophrenic and bipolar subjects (68--89%). No differences in APOD immunoreactivity were detected in occipital cortex (Brodmann's area 18) in either group, or in the hippocampus, substantia nigra, or cerebellum of the schizophrenic group. The low serum concentrations of APOD observed in these patients supports recent hypotheses involving systemic insufficiencies in lipid metabolism/signaling in schizophrenia. Elevation of APOD expression selectively within central nervous system regions implicated in the pathology of these neuropsychiatric disorders suggests a focal compensatory response that neuroleptic drug regimens may augment. |
| SCZ Keywords | schizophrenia, schizophrenic |
| 2 | Proc. Natl. Acad. Sci. U.S.A. 2001 Mar 98: 4066-71 |
|---|
| PMID | 11274430 |
| Title | Increased CNS levels of apolipoprotein D in schizophrenic and bipolar subjects: implications for the pathophysiology of psychiatric disorders. |
| Abstract | Chronic administration of the atypical antipsychotic drug, clozapine, to rodents has been shown to increase the concentration of apolipoprotein D (APOD) in several area of the brain, suggesting that APOD could be involved in the therapeutic effects of antipsychotic drugs and/or the pathology of psychotic illnesses. Here, we measured a significant decrease in the concentration of APOD in serum samples from schizophrenic patients. In contrast, APOD levels were significantly increased (92--287%) in dorsolateral prefrontal cortex (Brodmann's area 9) of schizophrenic and bipolar subjects. Elevated levels of APOD expression were also observed in the caudate of schizophrenic and bipolar subjects (68--89%). No differences in APOD immunoreactivity were detected in occipital cortex (Brodmann's area 18) in either group, or in the hippocampus, substantia nigra, or cerebellum of the schizophrenic group. The low serum concentrations of APOD observed in these patients supports recent hypotheses involving systemic insufficiencies in lipid metabolism/signaling in schizophrenia. Elevation of APOD expression selectively within central nervous system regions implicated in the pathology of these neuropsychiatric disorders suggests a focal compensatory response that neuroleptic drug regimens may augment. |
| SCZ Keywords | schizophrenia, schizophrenic |
| 3 | Schizophr. Res. 2002 Nov 58: 55-62 |
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| PMID | 12363390 |
| Title | Elevated plasma level of apolipoprotein D in schizophrenia and its treatment and outcome. |
| Abstract | Recently, apolipoprotein D (APOD), a protein that is involved in the essential polyunsaturated fatty acid (EPUFA) transport and metabolism, and neuronal growth and regeneration was reported to have increased in the postmortem brain and decreased in the serum of schizophrenia patients. We studied the plasma APOD levels in never-medicated schizophrenic patients at the onset of psychosis and in chronic patients with clozapine treatment. Plasma APOD levels were elevated in never-medicated patients at the first-episode of psychosis compared to normals (P = 0.047). Interestingly, the increase in APOD level was even more significant in chronic patients treated with clozapine compared to normals and first-episode patients (P = 0.008 and P = 0.03, respectively). The increased APOD level in never-medicated first-episode patients indicate that this increase probably predates the illness, since the duration of illness was < 5 days. Similarly, an even larger increase in APOD after clozapine treatment may be associated with its prophylactic effects, since the psychopathological scores were significantly reduced and the clozapine treatment has been found to increase the EPUFA membrane levels. These altered levels of APOD may help to understand the nature and possible mechanism of phospholipid membrane pathology in schizophrenia. |
| SCZ Keywords | schizophrenia, schizophrenic |
| 4 | Schizophr. Res. 2002 Nov 58: 55-62 |
|---|
| PMID | 12363390 |
| Title | Elevated plasma level of apolipoprotein D in schizophrenia and its treatment and outcome. |
| Abstract | Recently, apolipoprotein D (APOD), a protein that is involved in the essential polyunsaturated fatty acid (EPUFA) transport and metabolism, and neuronal growth and regeneration was reported to have increased in the postmortem brain and decreased in the serum of schizophrenia patients. We studied the plasma APOD levels in never-medicated schizophrenic patients at the onset of psychosis and in chronic patients with clozapine treatment. Plasma APOD levels were elevated in never-medicated patients at the first-episode of psychosis compared to normals (P = 0.047). Interestingly, the increase in APOD level was even more significant in chronic patients treated with clozapine compared to normals and first-episode patients (P = 0.008 and P = 0.03, respectively). The increased APOD level in never-medicated first-episode patients indicate that this increase probably predates the illness, since the duration of illness was < 5 days. Similarly, an even larger increase in APOD after clozapine treatment may be associated with its prophylactic effects, since the psychopathological scores were significantly reduced and the clozapine treatment has been found to increase the EPUFA membrane levels. These altered levels of APOD may help to understand the nature and possible mechanism of phospholipid membrane pathology in schizophrenia. |
| SCZ Keywords | schizophrenia, schizophrenic |
| 5 | Prostaglandins Leukot. Essent. Fatty Acids 2003 Dec 69: 421-7 |
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| PMID | 14623496 |
| Title | Apolipoprotein D modulates arachidonic acid signaling in cultured cells: implications for psychiatric disorders. |
| Abstract | Deficiencies in arachidonic acid (AA) parameters have been reported in schizophrenic patients. AA is a primary binding ligand for apolipoprotein D (APOD), which is increased in response to antipsychotic drug treatment and elevated in subjects with schizophrenia and bipolar disorder. In this study, we investigated whether APOD might modulate AA signaling/mobilization in cultured embryonic kidney (HEK) 293T cells. Immunofluorescent labeling revealed both cytosolic and membrane-bound expression of APOD protein in APOD-transfected cells. In cells expressing APOD, phorbal 12-myristate 13-acetate-induced AA release was inhibited compared to controls and membrane levels of AA were elevated, as indicated by the amount of AA maximally incorporated into membrane phospholipids. In addition, exogenous APOD added directly to the incubation media prevented cellular uptake of free [3H]AA. These results suggest that APOD acts to stabilize membrane-associated AA by preventing release and sequestering free AA in the cell. These actions of APOD may be beneficial to psychiatric patients. |
| SCZ Keywords | schizophrenia, schizophrenic |
| 6 | Prostaglandins Leukot. Essent. Fatty Acids 2003 Dec 69: 421-7 |
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| PMID | 14623496 |
| Title | Apolipoprotein D modulates arachidonic acid signaling in cultured cells: implications for psychiatric disorders. |
| Abstract | Deficiencies in arachidonic acid (AA) parameters have been reported in schizophrenic patients. AA is a primary binding ligand for apolipoprotein D (APOD), which is increased in response to antipsychotic drug treatment and elevated in subjects with schizophrenia and bipolar disorder. In this study, we investigated whether APOD might modulate AA signaling/mobilization in cultured embryonic kidney (HEK) 293T cells. Immunofluorescent labeling revealed both cytosolic and membrane-bound expression of APOD protein in APOD-transfected cells. In cells expressing APOD, phorbal 12-myristate 13-acetate-induced AA release was inhibited compared to controls and membrane levels of AA were elevated, as indicated by the amount of AA maximally incorporated into membrane phospholipids. In addition, exogenous APOD added directly to the incubation media prevented cellular uptake of free [3H]AA. These results suggest that APOD acts to stabilize membrane-associated AA by preventing release and sequestering free AA in the cell. These actions of APOD may be beneficial to psychiatric patients. |
| SCZ Keywords | schizophrenia, schizophrenic |
| 7 | Curr. Mol. Med. 2003 Aug 3: 408-18 |
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| PMID | 12942994 |
| Title | From pharmacotherapy to pathophysiology: emerging mechanisms of apolipoprotein D in psychiatric disorders. |
| Abstract | Apolipoprotein D (APOD) is an atypical plasma apolipoprotein and, based on its primary structure, it is a member of the lipocalin protein superfamily. Lipocalins have been extensively used as disease markers and, accordingly, APOD has become increasingly recognized as an important factor in the pathology of human neurodegenerative and neuropsychiatric disorders. APOD expression is increased in the plasma and brains of subjects with schizophrenia and bipolar disorder, suggesting that it acts as a marker for disease pathology. APOD also exhibits complex regulation by antipsychotic drug treatment and may represent a distinguishing mechanism of typical versus atypical drugs. The precise role of APOD in the CNS and disease remains to be elucidated, but recent findings have suggested that it plays an important role in the regulation of arachidonic acid signaling and metabolism providing further support for phospholipid membrane pathology in schizophrenia. |
| SCZ Keywords | schizophrenia, schizophrenic |
| 8 | J. Neurochem. 2003 Sep 86: 1089-100 |
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| PMID | 12911617 |
| Title | Antipsychotic drugs differentially modulate apolipoprotein D in rat brain. |
| Abstract | Apolipoprotein-D (APOD), a member of the lipocalin family of proteins, binds to arachidonic acid and cholesterol among other hydrophobic molecules. Recently, elevated APOD levels have been reported in the post-mortem brains, as well as plasma, of schizophrenic patients and in rodent brains after chronic treatment with clozapine (CLOZ). These findings and the evidence for altered membrane lipid metabolism in schizophrenia suggest that APOD may have a role in the pathophysiology of illness, and also in the differential clinical outcome following treatment with typical and atypical antipsychotic drugs. Here, we compared the effects of these antipsychotics on the expression of APOD in rat brain. Chronic treatment with typical antipsychotic, haloperidol (HAL) reduced APOD expression in hippocampus, piriform cortex and caudate-putamen (p = 0.027-0.002), whereas atypical antipsychotics, risperidone (RISP) and olanzapine (OLZ) increased (p = 0.051 to < 0.001 and p = 0.048 to < 0.001, respectively) APOD expression. In hippocampus, HAL-induced changes were present in CA1, CA3 and dentate gyrus, however, APOD levels in motor cortex were unchanged. There were also very dramatic effects of HAL on the neuronal morphology, particularly, cellular shrinkage and disorganization with the loss of neuropil. Post-treatment, either with RISP or OLZ, was very effective in restoring the HAL-induced reduction of APOD, as well as cellular morphology. Similarly, pre-treatments were also effective, but slightly less than post-treatment, in preventing HAL-induced reduction of APOD. The increased expression of APOD by atypical antipsychotics may reflect a novel molecular mechanism underlying their favorable effects compared with HAL on cognition, negative symptoms and extra-pyramidal symptoms in schizophrenia. |
| SCZ Keywords | schizophrenia, schizophrenic |
| 9 | J. Neurochem. 2003 Sep 86: 1089-100 |
|---|
| PMID | 12911617 |
| Title | Antipsychotic drugs differentially modulate apolipoprotein D in rat brain. |
| Abstract | Apolipoprotein-D (APOD), a member of the lipocalin family of proteins, binds to arachidonic acid and cholesterol among other hydrophobic molecules. Recently, elevated APOD levels have been reported in the post-mortem brains, as well as plasma, of schizophrenic patients and in rodent brains after chronic treatment with clozapine (CLOZ). These findings and the evidence for altered membrane lipid metabolism in schizophrenia suggest that APOD may have a role in the pathophysiology of illness, and also in the differential clinical outcome following treatment with typical and atypical antipsychotic drugs. Here, we compared the effects of these antipsychotics on the expression of APOD in rat brain. Chronic treatment with typical antipsychotic, haloperidol (HAL) reduced APOD expression in hippocampus, piriform cortex and caudate-putamen (p = 0.027-0.002), whereas atypical antipsychotics, risperidone (RISP) and olanzapine (OLZ) increased (p = 0.051 to < 0.001 and p = 0.048 to < 0.001, respectively) APOD expression. In hippocampus, HAL-induced changes were present in CA1, CA3 and dentate gyrus, however, APOD levels in motor cortex were unchanged. There were also very dramatic effects of HAL on the neuronal morphology, particularly, cellular shrinkage and disorganization with the loss of neuropil. Post-treatment, either with RISP or OLZ, was very effective in restoring the HAL-induced reduction of APOD, as well as cellular morphology. Similarly, pre-treatments were also effective, but slightly less than post-treatment, in preventing HAL-induced reduction of APOD. The increased expression of APOD by atypical antipsychotics may reflect a novel molecular mechanism underlying their favorable effects compared with HAL on cognition, negative symptoms and extra-pyramidal symptoms in schizophrenia. |
| SCZ Keywords | schizophrenia, schizophrenic |
| 10 | Mol. Psychiatry 2003 Feb 8: 167-75 |
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| PMID | 12610649 |
| Title | Differences in neuroanatomical sites of apoD elevation discriminate between schizophrenia and bipolar disorder. |
| Abstract | We previously demonstrated that apolipoprotein D (APOD) levels are elevated in the dorsolateral prefrontal cortex and caudate obtained postmortem from subjects with schizophrenia and bipolar disorder compared to controls, suggesting a focal compensatory response to neuropathology associated with psychiatric disorders. We have now extended those studies by measuring APOD protein levels in additional brain regions from post-mortem samples of schizophrenic and bipolar disorder subjects using an enzyme-linked immunosorbent assay. Increased APOD levels were observed in the lateral prefrontal cortex (Brodmann Area 46) in both schizophrenia (46%) and bipolar disorder (111%), and in the orbitofrontal cortex (Brodmann Area 11) (44.3 and 37.9% for schizophrenia and bipolar disorder, respectively). However, differences between the disease groups were observed in other brain regions. In subjects with schizophrenia, but not bipolar disorder, APOD levels were significantly elevated in the amygdala (42.8%) and thalamus (31.7%), while in bipolar disorder, but not schizophrenia, additional increases were detected in the parietal cortex (Brodmann Area 40; 123%) and the cingulate cortex (Brodmann Area 24; 57.7%). These data demonstrate that there is anatomical overlap in the pathophysiologies of schizophrenia and bipolar disorder, as well as areas of pathology that distinguish the two disorders. |
| SCZ Keywords | schizophrenia, schizophrenic |
| 11 | Mol. Psychiatry 2003 Feb 8: 167-75 |
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| PMID | 12610649 |
| Title | Differences in neuroanatomical sites of apoD elevation discriminate between schizophrenia and bipolar disorder. |
| Abstract | We previously demonstrated that apolipoprotein D (APOD) levels are elevated in the dorsolateral prefrontal cortex and caudate obtained postmortem from subjects with schizophrenia and bipolar disorder compared to controls, suggesting a focal compensatory response to neuropathology associated with psychiatric disorders. We have now extended those studies by measuring APOD protein levels in additional brain regions from post-mortem samples of schizophrenic and bipolar disorder subjects using an enzyme-linked immunosorbent assay. Increased APOD levels were observed in the lateral prefrontal cortex (Brodmann Area 46) in both schizophrenia (46%) and bipolar disorder (111%), and in the orbitofrontal cortex (Brodmann Area 11) (44.3 and 37.9% for schizophrenia and bipolar disorder, respectively). However, differences between the disease groups were observed in other brain regions. In subjects with schizophrenia, but not bipolar disorder, APOD levels were significantly elevated in the amygdala (42.8%) and thalamus (31.7%), while in bipolar disorder, but not schizophrenia, additional increases were detected in the parietal cortex (Brodmann Area 40; 123%) and the cingulate cortex (Brodmann Area 24; 57.7%). These data demonstrate that there is anatomical overlap in the pathophysiologies of schizophrenia and bipolar disorder, as well as areas of pathology that distinguish the two disorders. |
| SCZ Keywords | schizophrenia, schizophrenic |
| 12 | Schizophr. Res. 2005 Jan 72: 259-66 |
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| PMID | 15560970 |
| Title | Association of plasma apolipoproteins D with RBC membrane arachidonic acid levels in schizophrenia. |
| Abstract | Apolipoprotein D (APOD) is a member of the lipocalin superfamily of transporter proteins that bind small hydrophobic molecules, including arachidonic acid (AA). The ability of APOD to bind AA implicates it in pathways associated with membrane phospholipid signal transduction and metabolism. Recent findings of an increased expression of APOD in the mouse brain after clozapine treatment suggested a role for APOD in the pharmacological action of clozapine. Moreover, clozapine has been shown to increase membrane AA levels in RBC phospholipids from schizophrenic patients. APOD levels have also been shown to be elevated in the CNS of subjects with chronic schizophrenia, a disorder associated with AA dysfunction. In this study, we examined whether plasma APOD levels are related to red blood cell membrane AA contents in the first-episode neuroleptic-naive schizophrenic (FENNS) patients. Plasma APOD levels as measured by enzyme-linked immunosorbent assay (ELISA) were not significantly different (F = 0.51, df = 2,86, p = 0.60) among healthy controls (n = 36), FENNS patients (n = 33) and patients with other psychiatric disorders (n = 19). However, plasma APOD levels were significantly correlated with RBC-AA (p = 0.0022) and docosapentaenoic acid (p = 0.0008) in FENNS patients. There are several known mechanisms that can lead to the type of membrane fatty acid defects that have been identified in schizophrenia. Whether plasma APOD alone is a major determinant of reduced RBC membrane AA levels in FENNS patients remains to be determined, although these preliminary data appear not to support this premise. Taken together with other in vitro studies, however, the present data support the view that an increased expression of APOD such as induced by atypical neuroleptic drug, may facilitate incorporation of AA into membrane phospholipids by its selective binding to AA. |
| SCZ Keywords | schizophrenia, schizophrenic |
| 13 | Schizophr. Res. 2005 Jan 72: 259-66 |
|---|
| PMID | 15560970 |
| Title | Association of plasma apolipoproteins D with RBC membrane arachidonic acid levels in schizophrenia. |
| Abstract | Apolipoprotein D (APOD) is a member of the lipocalin superfamily of transporter proteins that bind small hydrophobic molecules, including arachidonic acid (AA). The ability of APOD to bind AA implicates it in pathways associated with membrane phospholipid signal transduction and metabolism. Recent findings of an increased expression of APOD in the mouse brain after clozapine treatment suggested a role for APOD in the pharmacological action of clozapine. Moreover, clozapine has been shown to increase membrane AA levels in RBC phospholipids from schizophrenic patients. APOD levels have also been shown to be elevated in the CNS of subjects with chronic schizophrenia, a disorder associated with AA dysfunction. In this study, we examined whether plasma APOD levels are related to red blood cell membrane AA contents in the first-episode neuroleptic-naive schizophrenic (FENNS) patients. Plasma APOD levels as measured by enzyme-linked immunosorbent assay (ELISA) were not significantly different (F = 0.51, df = 2,86, p = 0.60) among healthy controls (n = 36), FENNS patients (n = 33) and patients with other psychiatric disorders (n = 19). However, plasma APOD levels were significantly correlated with RBC-AA (p = 0.0022) and docosapentaenoic acid (p = 0.0008) in FENNS patients. There are several known mechanisms that can lead to the type of membrane fatty acid defects that have been identified in schizophrenia. Whether plasma APOD alone is a major determinant of reduced RBC membrane AA levels in FENNS patients remains to be determined, although these preliminary data appear not to support this premise. Taken together with other in vitro studies, however, the present data support the view that an increased expression of APOD such as induced by atypical neuroleptic drug, may facilitate incorporation of AA into membrane phospholipids by its selective binding to AA. |
| SCZ Keywords | schizophrenia, schizophrenic |
| 14 | Neuropsychobiology 2006 -1 54: 40-4 |
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| PMID | 16966838 |
| Title | Analysis of the association between Apolipoprotein D and schizophrenia. |
| Abstract | schizophrenia is a severe, chronic and common complex debilitating mental illness with a large genetic component. Evidence to date suggests that apolipoprotein D protein may be closely related to schizophrenia. To investigate the role of the APOD gene in the etiology of schizophrenia, we genotyped three genetic polymorphisms (rs7659, rs2280520 and rs4677695) in a case-control study using subjects from the Chinese population, and altogether 425 cases and 473 controls were analyzed in the study. However, we found no significant discrepancies in allele and genotype frequencies of the three polymorphisms nor in the haplotype distribution between the cases and the controls. Our data indicate no direct evidence of association between schizophrenia and the APOD gene, and the results suggest that the three genetic polymorphisms within the APOD gene are unlikely to confer increased susceptibility to the illness in the Chinese population. |
| SCZ Keywords | schizophrenia, schizophrenic |
| 15 | Curr. Biol. 2006 Apr 16: 674-9 |
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| PMID | 16581512 |
| Title | Overexpression of a Drosophila homolog of apolipoprotein D leads to increased stress resistance and extended lifespan. |
| Abstract | Increased Apolipoprotein D (APOD) expression has been reported in various neurological disorders, including Alzheimer's disease, schizophrenia, and stroke, and in the aging brain . However, whether APOD is toxic or a defense is unknown. In a screen to identify genes that protect Drosophila against acute oxidative stress, we isolated a fly homolog of APOD, Glial Lazarillo (GLaz). In independent transgenic lines, overexpression of GLaz resulted in increased resistance to hyperoxia (100% O(2)) as well as a 29% extension of lifespan under normoxia. These flies also displayed marked improvements in climbing and walking ability after sublethal exposure to hyperoxia. Overexpression of Glaz also increased resistance to starvation without altering lipid or protein content. To determine whether GLaz might be important in protection against reperfusion injury, we subjected the flies to hypoxia, followed by recovery under normoxia. Overexpression of GLaz was protective against behavioral deficits caused in normal flies by this ischemia/reperfusion paradigm. This and the accompanying paper by Sanchez et al. (in this issue of Current Biology) are the first to manipulate the levels of an APOD homolog in a model organism. Our data suggest that human APOD may play a protective role and thus may constitute a therapeutic target to counteract certain neurological diseases. |
| SCZ Keywords | schizophrenia, schizophrenic |
| 16 | Prog. Neuropsychopharmacol. Biol. Psychiatry 2010 Mar 34: 271-8 |
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| PMID | 19963028 |
| Title | Decreased kainate receptors in the hippocampus of apolipoprotein D knockout mice. |
| Abstract | Apolipoprotein D (APOD) has many actions critical to maintaining mammalian CNS function. It is therefore significant that levels of APOD have been shown to be altered in the CNS of subjects with schizophrenia, suggesting a role for APOD in the pathophysiology of the disorder. There is also a large body of evidence that cortical and hippocampal glutamatergic, serotonergic and cholinergic systems are affected by the pathophysiology of schizophrenia. Thus, we decided to use in vitro radioligand binding and autoradiography to measure levels of ionotropic glutamate, some muscarinic and serotonin 2A receptors in the CNS of APOD(-/-) and isogenic wild-type mice. These studies revealed a 20% decrease (mean+/-SEM: 104+/-10.2 vs. 130+/-10.4 fmol/mg ETE) in the density of kainate receptors in the CA 2-3 of the APOD(-/-) mice. In addition there was a global decrease in AMPA receptors (F(1,214)=4.67, p<0.05) and a global increase in muscarinic M2/M4 receptors (F(1,208)=22.77, p<0.0001) in the APOD(-/-) mice that did not reach significance in any single cytoarchitectural region. We conclude that glutamatergic pathways seem to be particularly affected in APOD(-/-) mice and this may contribute to the changes in learning and memory, motor tasks and orientation-based tasks observed in these animals, all of which involve glutamatergic neurotransmission. |
| SCZ Keywords | schizophrenia, schizophrenic |
| 17 | Neurobiol. Aging 2014 Jul 35: 1632-42 |
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| PMID | 24612673 |
| Title | Apolipoprotein D takes center stage in the stress response of the aging and degenerative brain. |
| Abstract | Apolipoprotein D (APOD) is an ancient member of the lipocalin family with a high degree of sequence conservation from insects to mammals. It is not structurally related to other major apolipoproteins and has been known as a small, soluble carrier protein of lipophilic molecules that is mostly expressed in neurons and glial cells within the central and peripheral nervous system. Recent data indicate that APOD not only supplies cells with lipophilic molecules, but also controls the fate of these ligands by modulating their stability and oxidation status. Of particular interest is the binding of APOD to arachidonic acid and its derivatives, which play a central role in healthy brain function. APOD has been shown to act as a catalyst in the reduction of peroxidized eicosanoids and to attenuate lipid peroxidation in the brain. Manipulating its expression level in fruit flies and mice has demonstrated that APOD has a favorable effect on both stress resistance and life span. The APOD gene is the gene that is upregulated the most in the aging human brain. Furthermore, APOD levels in the nervous system are elevated in a large number of neurologic disorders including Alzheimer's disease, schizophrenia, and stroke. There is increasing evidence for a prominent neuroprotective role of APOD because of its antioxidant and anti-inflammatory activity. APOD emerges as an evolutionarily conserved anti-stress protein that is induced by oxidative stress and inflammation and may prove to be an effective therapeutic agent against a variety of neuropathologies, and even against aging. |
| SCZ Keywords | schizophrenia, schizophrenic |