Biomedical subjects

Cheryl Mayo

Publications and source records attributed to Cheryl Mayo.

3 recordsLinked to original sources

PubMed2006

Combined application of behavior genetics and microarray analysis to identify regional expression themes and gene-behavior associations.

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.

Alcoholism↗

PubMed2005

The interaction of methylphenidate and benztropine with the dopamine transporter is different than other substrates and ligands.

A substantial body of evidence suggests that the dopamine transporter (DAT) is the principal site for cocaine-induced reward and euphoria. Interactions between the DAT and its substrates and ligands may therefore be of clinical relevance. The pharmacological characteristics of DAT compounds were compared in wild type (WT) and mutant DATs. The DAT mutants chosen for study were those with reduced binding and uptake activities (aspartic acid 79 mutated to alanine, termed D79A), reduced binding but normal uptake (tyrosine 251 mutated to alanine, termed Y251A; tyrosine 273 mutated to alanine, termed, Y273A), and normal binding but reduced uptake (a double mutation: serines 356 and 359 mutated to alanine, termed S356,359A). The WT and mutant DATs were transfected into COS-7 cells, and their pharmacological activities were examined 3 days later. Different patterns of pharmacological activity emerged. GBR 12909, cocaine, and mazindol each showed reduced affinity for the Y251A and the Y273A mutants, but their affinity for the S356,359A mutant was similar to that of the WT DAT. d-Amphetamine, MPP+, and dopamine each showed reduced affinity for the S356,359A mutant. Benztropine and methylphenidate had a different effect. Relative to the WT DAT, they both showed reduced affinity for the S356,359A mutant when displacing radioactive carboxyfluorotropane (CFT) binding, but similar affinity when inhibiting radioactive dopamine uptake. These results indicate that methylphenidate and benztropine may interact with the DAT in a different fashion then other substrates and ligands.

Amino Acid Sequence↗

PubMed2005

Prenatal exposure to a repeated variable stress paradigm elicits behavioral and neuroendocrinological changes in the adult offspring: potential relevance to schizophrenia.

Exposure to stress during gestation induces marked changes in the behavior of the affected offspring. Examining the consequences of prenatal stress may prove useful in understanding more about the origins of schizophrenia because a number of clinical investigations have suggested that developmental insults are associated with an increased incidence of schizophrenia. The purpose of these studies is to investigate the effects of stress during gestation on the behaviors of the adult male rat offspring with an emphasis on developing a heuristic animal model of schizophrenia. Pregnant female Sprague-Dawley rats were exposed to a novel variable stress paradigm during either the second or third week of gestation. Behavioral and neuroendocrinological consequences of prenatal stress exposure were evaluated in the male offspring on postnatal day 35 or 56. Prenatal stress exposure during the third week of pregnancy caused adult male rats to exhibit prolonged elevation in plasma glucocorticoid levels following acute exposure to restraint stress indicative of diminished glucocorticoid negative feedback. Similarly, exposure to stress during the third week of pregnancy elicited an enhanced locomotor response to the psychomotor stimulant amphetamine on postnatal day 56 but not on postnatal day 35. In addition, prepulse inhibition of the acoustic startle response was diminished across a range of prepulse stimulus intensities in prenatally stressed adult male rats. Similarly, prenatally stressed rats showed evidence of a disruption in auditory sensory gating as measured by the N40 response. Taken together, these findings suggest that prenatal stress exposure significantly changed many facets of adult rat behavior. Interestingly, the behaviors that are altered have been used to validate animal models of schizophrenia and therefore, suggest that this preparation may be useful to learn more about some aspects of the pathophysiology of schizophrenia.

Age Factors↗