Functional genomics and psychiatric illness

Hasenkamp, Wendy; Hemby, Scott E.

doi:10.1016/s0079-6123(02)38087-7

Cited by 8 publications

(5 citation statements)

References 72 publications

(54 reference statements)

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“…Furthermore, we show that the differential regulation of histone methylation levels across various genomic loci remain detectable in human brain samples across a wide range of postmortem intervals and tissue pH. It is important to note that until now, analysis of mRNA levels was the only method available to measure gene expression activity in postmortem human and primate brain (Hasenkamp and Hemby, 2002;Pongrac et al, 2002). We predict that chromatin-based approaches, including histone methylation mapping, will become a valuable complement to mRNA profiling and could provide mechanistic insight into transcriptional regulation of specific genes in healthy and diseased human brain.…”

Section: Resultsmentioning

confidence: 69%

Chromatin immunoprecipitation in postmortem brain

Huang

Matevossian

Jiang

et al. 2006

Journal of Neuroscience Methods

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Section: Resultsmentioning

confidence: 69%

Chromatin immunoprecipitation in postmortem brain

Huang

Matevossian

Jiang

et al. 2006

Journal of Neuroscience Methods

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“…Previously, we have employed similar approaches to identify molecular profiles of other diseases in human brain tissue including Alzheimer's disease, schizophrenia, drug abuse, as well as normal aging (Ginsberg et al . 2000; Hasenkamp and Hemby 2002; Hemby et al . 2002, 2003).…”

Section: Discussionmentioning

confidence: 99%

Molecular profiling of midbrain dopamine regions in cocaine overdose victims

Tang

Fasulo

Mash

et al. 2003

Journal of Neurochemistry

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Chronic cocaine use in humans and animal models is known to lead to pronounced alterations in neuronal function in brain regions associated with drug reinforcement. To evaluate whether the alterations in gene expression in cocaine overdose victims are associated with specific dopamine populations in the midbrain, cDNA arrays and western blotting were used to compare gene and protein expression patterns between cocaine overdose victims and age-matched controls in the ventral tegmental area (VTA) and lateral substantia nigra (l-SN). Array analysis revealed significant up-regulation of numerous transcripts in the VTA, but not in the l-SN, of cocaine overdose victims including NMDAR1, GluR2, GluR5 and KA2 receptor mRNA (p < 0.05). No significant alterations between overdose victims and controls were observed for GluR1, R3 or R4 mRNA levels. Correspondingly, western blot analysis revealed VTA-selective up-regulation of CREB (p < 0.01), NMDAR1 (p < 0.01), GluR2 (p < 0.05), GluR5 (p < 0.01) and KA2 (p < 0.05) protein levels of cocaine overdose victims. The present results indicate that selective alterations of CREB and certain ionotropic glutamate receptor (iGluR) subtypes appear to be associated with chronic cocaine use in humans in a region-specific manner. Moreover, as subunit composition determines the functional properties of iGluRs, the observed changes may indicate alterations in the excitability of dopamine transmission underlying long-term biochemical and behavioral effects of cocaine in humans.

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“…Regional assessments of gene expression create an informative mosaic of expression level changes; however, determining the cellular origins of the gene expression has been complicated by cellular heterogeneity of subcortical brain regions and the ability to assess multiple genes in discrete neuronal populations. Single cell gene expression methodology combined with array technology can overcome some of these limitations by assessing multiple transcripts in specific target neuronal populations, providing a level of assessment heretofore unattainable (Ginsberg et al, 2000;Hasenkamp and Hemby 2002;Hemby et al, 2002Hemby et al, , 2003Fasulo and Hemby, 2003;Kamme et al, 2003). Future studies directed toward protein confirmation and functional relevance of the observed mRNA change are warranted.…”

Section: Discussionmentioning

confidence: 99%

Discrete Cell Gene Profiling of Ventral Tegmental Dopamine Neurons after Acute and Chronic Cocaine Self-Administration

Backes

Hemby²

2003

J Pharmacol Exp Ther

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Chronic cocaine administration induces a number of biochemical alterations within the mesolimbic dopamine system that may mediate various aspects of the addictive process such as sensitization, craving, withdrawal, and relapse. In the present study, rats were allowed to self-administer cocaine (0.5 mg/ infusion) for 1 or 20 days. Tyrosine hydroxylase immunopositive cells were microdissected from the ventral tegmental area (VTA) using laser capture microdissection, and changes in the abundances of 95 mRNAs were assessed using cDNA macroarrays. Five GABA-A receptor subunit mRNAs (␣4, ␣6, ␤2, ␥2, and ␦) were down-regulated at both 1 and 20 days of cocaine selfadministration. In contrast, the catalytic subunit of protein phosphatase 2A (PP2␣), GABA-A ␣1, and G␣ i2 were significantly increased at both time points. Additionally, calcium/ calmodulin-dependent protein kinase II␣ mRNA levels were increased initially followed by a slight decrease after 20 days, whereas neuronal nitric-oxide synthase mRNA levels were initially decreased but returned to near control levels by day 20. These results indicate that alterations of specific GABA-A receptor subtypes and other signal transduction transcripts seem to be specific neuroadaptations associated with cocaine selfadministration. Moreover, as subunit composition determines the functional properties of GABA-A receptors, the observed changes may indicate alterations in the excitability of dopamine transmission underlying long-term biochemical and behavioral effects of cocaine.

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Functional genomics and psychiatric illness

Cited by 8 publications

References 72 publications

Chromatin immunoprecipitation in postmortem brain

Chromatin immunoprecipitation in postmortem brain

Molecular profiling of midbrain dopamine regions in cocaine overdose victims

Discrete Cell Gene Profiling of Ventral Tegmental Dopamine Neurons after Acute and Chronic Cocaine Self-Administration

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