Marty Green - Academia.edu (original) (raw)

Papers by Marty Green

Biological Psychiatry, 2000

Background: Substantial evidence indicates that lithium may exert its therapeutic effects through... more Background: Substantial evidence indicates that lithium may exert its therapeutic effects through progressive adaptive changes at the level of gene expression; however, the study of lithium-regulated genes has been primarily undertaken with the "candidate gene" approach based on a specific testable hypothesis. The aim of our study was to identify lithium-regulated genes that would not be predicted a priori by the candidate gene approach. Methods: Differential display polymerase chain reaction was used to isolate and identify messenger RNAs (mRNAs) that are differentially expressed in the frontal cortex of rats given lithium for 5 weeks to achieve plasma lithium concentrations of 0.6 to 0.9 mmol/L. Results: A putative lithium-regulated complementary DNA fragment (LRG1) was identified. Northern blot analysis revealed that 5 weeks of lithium treatment, but not 1 week, significantly reduced LRG1 mRNA levels. LRG1 mRNA levels were similarly reduced by 5 weeks of carbamazepine, but not valproate administration. Sequence analysis and search of the GenBank database revealed that LRG1 is analogous to the sequence of the gene for rat aldolase A. Conclusions: These results demonstrate that chronic administration of lithium, but not short-term administration, downregulates the levels of aldolase A mRNA, suggesting this effect may play a role in mediating the therapeutic action of this agent. Biol Psychiatry 2000;48: 58 -64

Neuropsychopharmacology, 2001

The mechanisms underlying the therapeutic effects of lithium are largely unknown but may involve ... more The mechanisms underlying the therapeutic effects of lithium are largely unknown but may involve progressive adaptive alterations at the level of gene expression. Using differential display PCR, we identify a novel cDNA fragment, the expression of which was increased in the rat frontal cortex after 5 weeks of lithium administration. A full-length cDNA (2954-nt) was cloned by arrayed cDNA library screening, and sequencing of the clone revealed an open reading frame of 537-bp encoding a 179-residue protein. Amino acid sequence comparisons revealed that our clone is a member of the Nudix hydrolase family, with the highest percentage of homology (95%) being with a subtype of human diphosphoinositol polyphosphate phosphohydrolase, hDIPP2. Northern blot analysis revealed that chronic lithium treatment significantly increased rDIPP2 mRNA levels in frontal cortex, but not in hippocampus, midbrain, and cerebellum. The effect of lithium on rDIPP2 mRNA expression was not shared by two other anticonvulsant mood stabilizers, carbamazepine and valproate. Time-course studies showed that 1-week of lithium had no effect on rDIPP2 mRNA abundance in the frontal cortex. Our results suggest that DIPP2 may represent a biologically relevant target of lithium therapy, further supporting the notion that abnormalities in inositol phosphate metabolism may be significant in the pathophysiology and pharmacotherapy of bipolar disorder.

Neuropsychopharmacology, 2001

The latency in onset of antimanic and mood stabilizing effects of lithium suggest that long-term ... more The latency in onset of antimanic and mood stabilizing effects of lithium suggest that long-term neuronal adaptations mediated by changes in gene expression may be important to the therapeutic action of lithium treatment. Using differential display-polymerase chain reaction, several novel, hitherto unexpected lithium-regulated genes have been isolated, all of which would not have been predicted with the candidate gene approach. During the process of characterizing one of these novel genes, we have identified a cDNA clone, a homolog of human/mouse transmembrane-4-superfamily (also known as tetraspan) protein, CD151, the expression of which was significantly decreased in rat frontal cortex following chronic (five weeks) lithium treatment. The reduction of CD151 mRNA levels was also observed following chronic administration of carbamazepine and valproate. Conversely, the expression of CD151 was not altered by short-term (one week) lithium treatment and by chronic administration of the tricyclic antidepressant, imipramine, or the typical antipsychotic, haloperidol, further demonstrating time dependence and pharmacological specificity of this effect. Our studies, thus, indicate that CD151 may represent a therapeutically relevant target common to lithium and the anticonvulsant mood stabilizing drugs, carbamazepine and valproate.

Neuroscience Letters, 1995

firmed in eggs using high-performance liquid chroma-ABSTRACT: The olfactory and accessory lobes t... more firmed in eggs using high-performance liquid chroma-ABSTRACT: The olfactory and accessory lobes tography with electrochemical detection. Morphometconstitute prominent histological structures within the ric analyses suggested that serotonin depletion larval and mature lobster deutocerebrum, and both dramatically slowed the growth of olfactory and accesare associated with a dense innervation from paired sory lobes, although glomeruli differentiated at the serotonergic nerve cells, the dorsal giant neurons normal time in both areas. The toxin exhibited a high (DGNs). During development, the cell bodies of the degree of specificity for serotonergic neurons and as-DGNs are the first central somata to express serotonin sociated target regions, and serotonin depletion per-(5-HT), and the onset of their 5-HT immunoreactivity sisted for at least 2 months following treatment. The coincides with the beginning of accessory lobe formagoal of future experiments is to determine which of the tion. In contrast, the olfactory lobe anlagen emerge cell types that innervate the olfactory and accessory much earlier and grow in the apparent absence of lobes are affected by toxin treatment, thereby resulting serotonin. The role of serotonergic input for the develin the retarded growth of these areas. ᭧ 1997 John opment of these brain structures was investigated in Wiley & Sons, Inc. J Neurobiol 33: 357-373, 1997 lobster embryos after serotonin had been depleted Keywords: 5,7-dihydroxytryptamine; serotonin; olfacpharmacologically with the neurotoxin 5,7-dihydroxytory lobes; accessory lobes; development tryptamine. A Ç90% reduction of serotonin was con-Correspondence to: B. S. Beltz shown that serotonin can inhibit (Haydon et al.,

Biological Psychiatry, 2000

Background: Substantial evidence indicates that lithium may exert its therapeutic effects through... more Background: Substantial evidence indicates that lithium may exert its therapeutic effects through progressive adaptive changes at the level of gene expression; however, the study of lithium-regulated genes has been primarily undertaken with the "candidate gene" approach based on a specific testable hypothesis. The aim of our study was to identify lithium-regulated genes that would not be predicted a priori by the candidate gene approach. Methods: Differential display polymerase chain reaction was used to isolate and identify messenger RNAs (mRNAs) that are differentially expressed in the frontal cortex of rats given lithium for 5 weeks to achieve plasma lithium concentrations of 0.6 to 0.9 mmol/L. Results: A putative lithium-regulated complementary DNA fragment (LRG1) was identified. Northern blot analysis revealed that 5 weeks of lithium treatment, but not 1 week, significantly reduced LRG1 mRNA levels. LRG1 mRNA levels were similarly reduced by 5 weeks of carbamazepine, but not valproate administration. Sequence analysis and search of the GenBank database revealed that LRG1 is analogous to the sequence of the gene for rat aldolase A. Conclusions: These results demonstrate that chronic administration of lithium, but not short-term administration, downregulates the levels of aldolase A mRNA, suggesting this effect may play a role in mediating the therapeutic action of this agent. Biol Psychiatry 2000;48: 58 -64

Neuropsychopharmacology, 2001

The mechanisms underlying the therapeutic effects of lithium are largely unknown but may involve ... more The mechanisms underlying the therapeutic effects of lithium are largely unknown but may involve progressive adaptive alterations at the level of gene expression. Using differential display PCR, we identify a novel cDNA fragment, the expression of which was increased in the rat frontal cortex after 5 weeks of lithium administration. A full-length cDNA (2954-nt) was cloned by arrayed cDNA library screening, and sequencing of the clone revealed an open reading frame of 537-bp encoding a 179-residue protein. Amino acid sequence comparisons revealed that our clone is a member of the Nudix hydrolase family, with the highest percentage of homology (95%) being with a subtype of human diphosphoinositol polyphosphate phosphohydrolase, hDIPP2. Northern blot analysis revealed that chronic lithium treatment significantly increased rDIPP2 mRNA levels in frontal cortex, but not in hippocampus, midbrain, and cerebellum. The effect of lithium on rDIPP2 mRNA expression was not shared by two other anticonvulsant mood stabilizers, carbamazepine and valproate. Time-course studies showed that 1-week of lithium had no effect on rDIPP2 mRNA abundance in the frontal cortex. Our results suggest that DIPP2 may represent a biologically relevant target of lithium therapy, further supporting the notion that abnormalities in inositol phosphate metabolism may be significant in the pathophysiology and pharmacotherapy of bipolar disorder.

Neuropsychopharmacology, 2001

The latency in onset of antimanic and mood stabilizing effects of lithium suggest that long-term ... more The latency in onset of antimanic and mood stabilizing effects of lithium suggest that long-term neuronal adaptations mediated by changes in gene expression may be important to the therapeutic action of lithium treatment. Using differential display-polymerase chain reaction, several novel, hitherto unexpected lithium-regulated genes have been isolated, all of which would not have been predicted with the candidate gene approach. During the process of characterizing one of these novel genes, we have identified a cDNA clone, a homolog of human/mouse transmembrane-4-superfamily (also known as tetraspan) protein, CD151, the expression of which was significantly decreased in rat frontal cortex following chronic (five weeks) lithium treatment. The reduction of CD151 mRNA levels was also observed following chronic administration of carbamazepine and valproate. Conversely, the expression of CD151 was not altered by short-term (one week) lithium treatment and by chronic administration of the tricyclic antidepressant, imipramine, or the typical antipsychotic, haloperidol, further demonstrating time dependence and pharmacological specificity of this effect. Our studies, thus, indicate that CD151 may represent a therapeutically relevant target common to lithium and the anticonvulsant mood stabilizing drugs, carbamazepine and valproate.

Neuroscience Letters, 1995

firmed in eggs using high-performance liquid chroma-ABSTRACT: The olfactory and accessory lobes t... more firmed in eggs using high-performance liquid chroma-ABSTRACT: The olfactory and accessory lobes tography with electrochemical detection. Morphometconstitute prominent histological structures within the ric analyses suggested that serotonin depletion larval and mature lobster deutocerebrum, and both dramatically slowed the growth of olfactory and accesare associated with a dense innervation from paired sory lobes, although glomeruli differentiated at the serotonergic nerve cells, the dorsal giant neurons normal time in both areas. The toxin exhibited a high (DGNs). During development, the cell bodies of the degree of specificity for serotonergic neurons and as-DGNs are the first central somata to express serotonin sociated target regions, and serotonin depletion per-(5-HT), and the onset of their 5-HT immunoreactivity sisted for at least 2 months following treatment. The coincides with the beginning of accessory lobe formagoal of future experiments is to determine which of the tion. In contrast, the olfactory lobe anlagen emerge cell types that innervate the olfactory and accessory much earlier and grow in the apparent absence of lobes are affected by toxin treatment, thereby resulting serotonin. The role of serotonergic input for the develin the retarded growth of these areas. ᭧ 1997 John opment of these brain structures was investigated in Wiley & Sons, Inc. J Neurobiol 33: 357-373, 1997 lobster embryos after serotonin had been depleted Keywords: 5,7-dihydroxytryptamine; serotonin; olfacpharmacologically with the neurotoxin 5,7-dihydroxytory lobes; accessory lobes; development tryptamine. A Ç90% reduction of serotonin was con-Correspondence to: B. S. Beltz shown that serotonin can inhibit (Haydon et al.,