Biomedical subjects

Melville M Leitch

Publications and source records attributed to Melville M Leitch.

4 recordsLinked to original sources

PubMed2006

Assessing cortisol and dehydroepiandrosterone (DHEA) in saliva: effects of collection method.

An increasing number of studies are utilizing saliva sampling as a method of assessing adrenal steroid secretion. Saliva samples have certain advantages over plasma, being non-invasive and easily collected. However, some methods of collection may compromise the accuracy of the assay, particularly those which employ aids to stimulate saliva production. We sought to compare the accuracy of cortisol and dehydroepiandrosterone (DHEA) measurement by examining the association between plasma levels, saliva and saliva collected using a citric acid-treated salivette device. Twenty six healthy male volunteers were recruited for the study. To increase the range of steroid levels in the samples collected, half the subjects were pre-treated with hydrocortisone (20mg, twice a day for 7 days) and half with placebo. Saliva samples were then collected from each subject using both a 'passive drool' method and a citric acid-treated salivette. A plasma sample was also collected. Cortisol and DHEA levels were measured by radioimmunoassay. For cortisol levels, both methods of saliva collection correlated highly with plasma levels and with each other (r 0.85; R(2) 0.72 for all). For DHEA levels, only saliva samples collected using the unstimulated collection method correlated with plasma levels. DHEA collected using the salivette device did not correlate significantly with either plasma or the unstimulated saliva (r 0.2;R(2) 0.04). It is crucial that future studies are aware of these issues and are cognizant of the effects of the method of collection when examining steroid levels in saliva.

Adolescent↗

PubMed2003

Flattening the glucocorticoid rhythm causes changes in hippocampal expression of messenger RNAs coding structural and functional proteins: implications for aging and depression.

Subtle changes in glucocorticoid levels, including a flattening of the diurnal rhythm with raised nadir, are prevalent, being characteristic of both aging and major depression. Both these conditions are also associated with deficits in hippocampally mediated cognitive functions. We hypothesized that this profile of glucocorticoid levels causes structural and functional changes in the hippocampus, which in turn may engender cognitive deficits. We implanted slow-release corticosterone pellets into adrenally intact adult male rats to produce a flattened glucocorticoid rhythm with levels clamped midway between the normal nadir and zenith. Using density profile analysis we measured hippocampal expression of messenger RNAs encoding structural and functional proteins. In rats with a flattened glucocorticoid rhythm, the expression of the mRNA coding for microtubule associated protein-2b (MAP2b) was reduced in CA3 relative to sham-operated controls, but unchanged in dentate gyrus and CA1. In contrast, the expression of the mRNA coding the alpha subunit of calcium-calmodulin dependent kinase (CAMKIIalpha) was reduced in dentate gyrus in animals with a flattened glucocorticoid rhythm, but unchanged in CA3. The expression of the mRNA coding the synaptic vesicle protein synaptophysin was unchanged in both CA3 and dentate gyrus. The data indicate that a flattening of the normal diurnal glucocorticoid rhythm decreases the hippocampal expression of mRNAs coding key structural and functional proteins, and does so in a regionally selective manner. The data may have relevance for cognitive deficits characteristic of aging and depression.

Aging↗

PubMed2003

Flattening the corticosterone rhythm attenuates 5-HT1A autoreceptor function in the rat: relevance for depression.

Depression is associated with glucocorticoid abnormalities, in particular a flattening of the diurnal cortisol rhythm. Recent data suggest that an important factor in the aetiology of depression may be a deficit in the function and expression of 5-HT(1A) receptors, which has been reported in depressed patients. The present study assessed the possibility that this cortisol abnormality is causal in the 5-HT(1A) receptor deficits. First, a rat model of flattened glucocorticoid rhythm was developed. Controlled release corticosterone pellets implanted for 14 days flattened the corticosterone rhythm and maintained levels constant midway between the nadir and zenith levels observed in sham-operated rats. Secondly, using microdialysis to assess 5-HT release in the hippocampus, the inhibitory response to 8-OHDPAT was measured to determine the sensitivity of somatodendritic 5-HT(1A) autoreceptors. Corticosterone treatment was found to induce a significant attenuation in the response to 8-OHDPAT, indicating functional desensitization of somatodendritic 5-HT(1A) autoreceptors. There was no effect of corticosterone treatment on basal extracellular 5-HT levels. The data suggest that the glucocorticoid abnormalities associated with depression may impact on the functioning of 5-HT(1A) receptors in the brain. These findings suggest that resolution of cortisol abnormalities may be a valuable target for pharmacotherapy in the treatment of depression.

Animals↗

PubMed2003

Early life adversity programs changes in central 5-HT neuronal function in adulthood.

Early life adversity is associated with an increased incidence of psychiatric illness in adulthood. Although the mechanisms underlying this association are unclear, one possible substrate is brain 5-hydroxytryptamine neurotransmission, which is reportedly abnormal in several psychiatric disorders. This study examined the effect of a rat model of early life adversity, early maternal separation, on 5-hydroxytryptamine neurotransmission in adulthood. In vitro electrophysiological experiments revealed that, in early maternal separation rats compared with controls, the sensitivity of alpha1-adrenoceptors on 5-hydroxytryptamine neurons in the dorsal raphe nucleus was significantly reduced, whilst the sensitivity of 5-hydroxytryptamine1A receptors showed a nonsignificant trend to reduction. In in vivo microdialysis experiments, the 5-hydroxytryptamine1A receptor agonist-induced suppression of 5-hydroxytryptamine release in the frontal cortex was reduced in early maternal separation animals, suggesting desensitization of 5-hydroxytryptamine1A autoreceptors. There was no increase in basal 5-hydroxytryptamine in the frontal cortex as measured by microdialysis and a nonsignificant trend towards increased basal firing activity of classical (non-bursting) 5-hydroxytryptamine neurons in the dorsal raphe nucleus measured by in vivo electrophysiology. Finally, early maternal separation failed to alter expression of messenger ribonucleic acids coding for 5-hydroxytryptamine1A or alpha1B receptors in the dorsal raphe nucleus as measured by in situ hybridization histochemistry, suggesting that functional changes in receptor sensitivity observed are not due to changes in receptor gene transcription. The findings demonstrate that early life adversity programs changes in sensitivity of the two principal regulators of 5-hydroxytryptamine neuronal activity. Similar effects in humans may contribute to the increased incidence of psychiatric illness in individuals exposed to early life adversity.

8-Hydroxy-2-(di-n-propylamino)tetralin↗