Genotypic differences in ethanol sensitivity in two tests of motor incoordination

Crabbe, John C.; Metten, Pamela; Yu, Chia Hua; Schlumbohm, Jason P.; Cameron, Andy J.; Wahłsten, Douglas

doi:10.1152/japplphysiol.00132.2003

Cited by 67 publications

(84 citation statements)

References 38 publications

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“…Association analysis revealed that a number of genes encoding proteins in the NMDA/glutamate signaling pathway are involved in the ability to traverse a wire grid; however, the particular genes involved are dependent on whether or not the subjects are under the influence of ethanol (Crabbe et al, 2003). NOS, Grin1, and Grin2C mRNA levels are correlated positively with distance traveled by salinetreated animals.…”

Section: Region-enriched Genesmentioning

confidence: 99%

Combined Application of Behavior Genetics and Microarray Analysis to Identify Regional Expression Themes and Gene–Behavior Associations

Letwin¹,

Kafkafi²,

Benjamini³

et al. 2006

J. Neurosci.

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In this report we link candidate genes to complex behavioral phenotypes by using a behavior genetics approach. Gene expression signatures were generated for the prefrontal cortex, ventral striatum, temporal lobe, periaqueductal gray, and cerebellum in eight inbred strains from priority group A of the Mouse Phenome Project. Bioinformatic analysis of regionally enriched genes that were conserved across all strains revealed both functional and structural specialization of particular brain regions. For example, genes encoding proteins with demonstrated anti-apoptotic function were over-represented in the cerebellum, whereas genes coding for proteins associated with learning and memory were enriched in the ventral striatum, as defined by the Expression Analysis Systematic Explorer (EASE) application. Association of regional gene expression with behavioral phenotypes was exploited to identify candidate behavioral genes. Phenotypes that were investigated included anxiety, drug-naive and ethanol-induced distance traveled across a grid floor, and seizure susceptibility. Several genes within the glutamatergic signaling pathway (i.e., NMDA/glutamate receptor subunit 2C, calmodulin, solute carrier family 1 member 2, and glutamine synthetase) were identified in a phenotype-dependent and region-specific manner. In addition to supporting evidence in the literature, many of the genes that were identified could be mapped in silico to surrogate behavior-related quantitative trait loci. The approaches and data set described herein serve as a valuable resource to investigate the genetic underpinning of complex behaviors.

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Section: Region-enriched Genesmentioning

confidence: 99%

Combined Application of Behavior Genetics and Microarray Analysis to Identify Regional Expression Themes and Gene–Behavior Associations

Letwin¹,

Kafkafi²,

Benjamini³

et al. 2006

J. Neurosci.

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“…Experiments were performed as described by Crabbe et al (2003a). Briefly, mice were given four training trials on a balance beam (width, 19 mm; length, 90 cm).…”

Section: Ataxia Testingmentioning

confidence: 99%

Calcium-Stimulated Adenylyl Cyclases Are Critical Modulators of Neuronal Ethanol Sensitivity

et al. 2005

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The importance of the cAMP signaling pathway in the modulation of ethanol sensitivity has been suggested by studies in organisms from Drosophila melanogaster to man. However, the involvement of specific isoforms of adenylyl cyclase (AC), the molecule that converts ATP to cAMP, has not been systemically determined in vivo. Because AC1 and AC8 are the only AC isoforms stimulated by calcium, and ethanol modulates calcium flux by the NMDA receptor, we hypothesized that these ACs would be important in the neural response to ethanol. AC1 knock-out (KO) mice and double knock-out (DKO) mice with genetic deletion of both AC1 and AC8 display substantially increased sensitivity to ethanol-induced sedation compared with wild-type (WT) mice, whereas AC8 KO mice are only minimally more sensitive. In contrast, AC8 KO and DKO mice, but not AC1 KO mice, demonstrate decreased voluntary ethanol consumption compared with WT mice. DKO mice do not display increased sleep time compared with WT mice after administration of ketamine or pentobarbital, indicating that the mechanism of enhanced ethanol sensitivity in these mice is likely distinct from the antagonism of ethanol of the NMDA receptor and potentiation of the GABA A receptor. Ethanol does not enhance calcium-stimulated AC activity, but the ethanol-induced phosphorylation of a discrete subset of protein kinase A (PKA) substrates is compromised in the brains of DKO mice. These results indicate that the unique activation of PKA signaling mediated by the calcium-stimulated ACs is an important component of the neuronal response to ethanol.

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“…On the test day, animals received an intraperitoneal injection of 20% Et-OH (2 g/kg) or an equal volume of physiological saline. Behavioral tests were performed 10 min after the injection to allow ethanol concentration to reach the maximum level in the brain (Crabbe et al 2003).…”

Section: Behavioral Testsmentioning

confidence: 99%

Neuroprotective effect of small heat shock protein, Hsp27, after acute and chronic alcohol administration

Tóth

Gonda

Vı́gh

et al. 2010

Cell Stress and Chaperones

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Alcohol induces degeneration of neurons and inhibits neurogenesis in the brain. Small heat shock proteins are able to protect neurons in cerebral ischemia and oxidative stress. In this study, we investigated the neuroprotective effect of small heat shock protein, Hsp27, after acute and chronic ethanol administrations using transgenic mice overexpressing the human Hsp27 protein.Transgenic mice and wild-type littermates were injected with 2 g/kg ethanol intraperitoneally, and then motor coordination and muscle strength were analyzed using different behavioral tests, such as footprint analysis, balance beam, and inverted screen tests. Ethanol-injected transgenic mice showed similar footprints to control salineinjected mice, did not fall of the beam, and were able to climb to the top of the inverted screen, while wild-type mice showed ataxia and incoordination after ethanol injection. The effect of Hsp27 on chronic ethanol consumption was also investigated. Drinking water of mice was replaced by a 20% ethanol solution for 5 weeks, and then brain sections were stained with Fluoro Jade C staining. We found significantly lesser amount of degenerating neurons in the brain of ethanol-drinking transgenic mice compared to wild-type mice. We conclude that Hsp27 can protect neurons against the acute and chronic toxic effects of ethanol.

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Genotypic differences in ethanol sensitivity in two tests of motor incoordination

Cited by 67 publications

References 38 publications

Combined Application of Behavior Genetics and Microarray Analysis to Identify Regional Expression Themes and Gene–Behavior Associations

Combined Application of Behavior Genetics and Microarray Analysis to Identify Regional Expression Themes and Gene–Behavior Associations

Calcium-Stimulated Adenylyl Cyclases Are Critical Modulators of Neuronal Ethanol Sensitivity

Neuroprotective effect of small heat shock protein, Hsp27, after acute and chronic alcohol administration

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