Application of cDNA microarrays to examine gene expression differences in schizophrenia

Vawter, Marquis P.; Barrett, Tanya; Cheadle, Christopher; Sokolov, Boris P.; Wood, William H.; Donovan, David M.; Webster, Maree J.; Freed, William J.; Becker, Kevin G.

doi:10.1016/s0361-9230(01)00522-6

Cited by 230 publications

(187 citation statements)

References 29 publications

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“…HINT1 gene expression was decreased in two prior microarray studies of DLPFC in schizophrenia (10,11) and is confirmed by real-time Q-PCR to be about a 2.8-fold decrease. There is an overlap between cohorts in the microarray study (11) and the current Q-PCR study of 27 of the 43 brains assayed, thus the confirmation is not an independent replication.…”

Section: Hint1mentioning

confidence: 52%

“…Studies of patients with schizophrenia have used microarray to screen cortical (DLPFC, superior temporal gyrus, and entorhinal cortex) and cerebellar samples from a matched set of subject to determine genes that are differentially expressed (3)(4)(5)(6)(7)(8)(9)(10)(11). Broadly, these reports to date have suggested alterations in functional pathways involving myelin, synaptic, metabolic, and proteasome-ubiquitin related processes in schizophrenia, though the specific differences, their magnitude and directionality, have been inconsistent.…”

Section: Introductionmentioning

confidence: 99%

“…Previous microarray findings reported histidine triad nucleotide binding protein (HINT1) gene was down-regulated across four comparisons of patients with schizophrenia (10,11). These microarray comparisons used pools of RNA representing 20 patients and 20 controls.…”

Section: Introductionmentioning

confidence: 99%

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Gene Expression of Metabolic Enzymes and a Protease Inhibitor in the Prefrontal Cortex Are Decreased in Schizophrenia

et al. 2004

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Microarray expression studies have reported decreased mRNA expression of histidine triad nucleotide-binding protein (HINT1) and cytosolic malate dehydrogenase (MDH1) in the dorsolateral prefrontal cortex (DLPFC) of individuals with schizophrenia. Microarray results for neuroserpin (SERPINI1) mRNA in the DLPFC have reported increased and decreased expression in individuals with schizophrenia. The relative abundances of HINT1, MDH1, and SERPINI1 mRNA in the DLPFC in individuals with schizophrenia and controls were measured by real-time quantitative polymerase chain reaction (Q-PCR) and for HINT1 expression by in situ hybridization. The Q-PCR results were compared by analysis of covariance between individuals with schizophrenia and controls. Gene expression levels for HINT1, MDH1, and SERPINI1 were significantly different between the groups. The male individuals with schizophrenia compared to male controls showed reductions by 2.8-to 3.7-fold of HINT1, neuroserpin, and MDH1 by Q-PCR. The decreases in mRNA abundance for MDH1 (P ϭ 0.006), HINT1 (P ϭ 0.050), and neuroserpin (P ϭ 0.005) in DLPFC of male individuals with schizophrenia is consistent with prior reports. HINT1 mRNA was reduced significantly by 34% in layer VI. Though there were no significant interactions with gender, gene expression between female patients and the female control group did not differ. These results confirm earlier reports and suggest abnormalities of specific genes related to metabolic and protease activities in the DLPFC might be considered as part of a molecular pathway in male patients with schizophrenia.

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Section: Hint1mentioning

confidence: 52%

Section: Introductionmentioning

confidence: 99%

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Gene Expression of Metabolic Enzymes and a Protease Inhibitor in the Prefrontal Cortex Are Decreased in Schizophrenia

et al. 2004

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“…Microarray studies found significant decreases in expression of genes encoding proteins involving the malate shuttle, tricarboxylic acid (TCA) cycle, as well as the ornithine–polyamine, aspartate–alanine, and ubiquitin metabolism groups in the dorsolateral prefrontal cortex (DLPFC)(1-13). These changes were not attributable to antipsychotic treatment, which may have a restorative effect (11).…”

Section: Introductionmentioning

confidence: 99%

Neuron-specific deficits of bioenergetic processes in the dorsolateral prefrontal cortex in schizophrenia

et al. 2018

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Schizophrenia is a devastating illness that affects over 2 million people in the U.S. and costs society billions of dollars annually. New insights into the pathophysiology of schizophrenia are needed to provide the conceptual framework to facilitate development of new treatment strategies. We examined bioenergetic pathways in the dorsolateral prefrontal cortex (DLPFC) of subjects with schizophrenia and control subjects using western blot analysis, quantitative real-time polymerase chain reaction, and enzyme/substrate assays. Laser-capture microdissection-qPCR was used to examine these pathways at the cellular level. We found decreases in hexokinase (HXK) and phosphofructokinase (PFK) activity in the DLPFC, as well as decreased PFK1 mRNA expression. In pyramidal neurons, we found an increase in monocarboxylate transporter 1 mRNA expression, and decreases in HXK1, PFK1, glucose transporter 1 (GLUT1), and GLUT3 mRNA expression. These results suggest abnormal bioenergetic function, as well as a neuron-specific defect in glucose utilization, in the DLPFC in schizophrenia.

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“…In a microarray analysis, HINT1 mRNA expression was lower in the dorsolateral prefrontal cortex of patients who suffer from schizophrenic and bipolar disorder than healthy controls (Elashoff et al., 2007; Vawter et al., 2001, 2004). HINT1 is also associated with abuse of drugs, such as nicotine (Jackson et al., 2011).…”

Section: Introductionmentioning

confidence: 99%

Effects of Hint1 deficiency on emotional‐like behaviors in mice under chronic immobilization stress

Sun

Liu

et al. 2017

Brain and Behavior

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BackgroundHistidine triad nucleotide‐binding protein 1 (HINT1) is regarded as a haplo‐insufficient tumor suppressor and is closely associated with diverse neuropsychiatric diseases. Moreover, HINT1 is related to gender‐specific acute behavior changes in schizophrenia and in response to nicotine. Stress has a range of molecular effects in emotional disorders, which can cause a reduction in brain‐derived neurotrophic factor (BDNF) expression in the hippocampus, resulting in hippocampal atrophy and neuronal cell loss.MethodsThis study examined the role of HINT1 deficiency in anxiety‐related and depression‐like behaviors and BDNF expression in the hippocampus under chronic immobilization stress, and investigated whether the sex‐specific and haplo‐insufficient effects exist in emotional‐like behaviors under the same condition.ResultsIn a battery of behavior tests, the results of the control group, not exposed to stress, showed that knockout (KO) and heterozygosity (HT) of Hint1 had anxiolytic‐like and antidepression‐like effects on the male and female mice. However, both male and female Hint1‐KO mice showed elevated anxiety‐related and antidepression‐like behavior under chronic immobilization stress; moreover, both male and female Hint1‐HT mice displayed elevated anxiety‐related behavior and increased depression‐like behavior under chronic immobilization stress. There were no significant differences in general locomotor activity between Hint1‐KO and ‐HT mice and their wild‐type (WT) littermates. Hint1‐KO mice under basal and chronic immobilization stress conditions expressed more BDNF in the hippocampus than did Hint1‐HT and WT mice; overall, there were no significant sex differences in emotional‐like behaviors of Hint1‐KO and ‐HT mice. Additionally, Hint1‐HT mice showed haplo‐insufficient effects on emotional‐like behaviors under basic conditions, rather than under chronic immobilization stress.ConclusionsBoth male and female HINT 1 KO and HT mice had a trend of anxiolytic‐like behavior and antidepression‐like behavior at control group. However, both male and female HINT1 KO mice showed elevated anxiety‐related and antidepression‐like behavior under chronic immobilization stress; moreover, both male and female HINT1 HT mice displayed elevated anxiety‐related behavior and increased depression‐like behavior under chronic immobilization stress.

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Application of cDNA microarrays to examine gene expression differences in schizophrenia

Cited by 230 publications

References 29 publications

Gene Expression of Metabolic Enzymes and a Protease Inhibitor in the Prefrontal Cortex Are Decreased in Schizophrenia

Gene Expression of Metabolic Enzymes and a Protease Inhibitor in the Prefrontal Cortex Are Decreased in Schizophrenia

Neuron-specific deficits of bioenergetic processes in the dorsolateral prefrontal cortex in schizophrenia

Effects of Hint1 deficiency on emotional‐like behaviors in mice under chronic immobilization stress

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