Biomedical subjects
Publications and source records attributed to D C Daniels.
Catatonic syndromes are seen in diverse psychiatric and systemic illnesses, and may have varied presentations. Although reports suggest that benzodiazepines are helpful, debate persists regarding definitive treatment for catatonia. We present a case in which electroconvulsive therapy effectively resolved symptoms in an adolescent patient with catatonia who had only a transient response to lorazepam.
Repeated 6-h daily restraint stress over 21 days reduces length and number of branch points of hippocampal CA3c pyramidal dendrites in the hippocampal formation of adult male rats. This effect is mimicked by daily injections of 40 mg/kg corticosterone. Daily treatment with tianeptine (15 mg/kg) prior to stress sessions or the corticosterone treatment prevented these effects of stress or corticosterone, respectively. Tianeptine treatment did not prevent the effects of stress to increase adrenal/body weight ratio, nor did it prevent the effects of stress to decrease body weight gain, indicating that its actions are not mediated solely by effects on stress-induced secretion of corticosterone. Because tianeptine is known to enhance neural uptake of serotonin, these results suggest that the serotonergic system may be involved in modulating stress and corticosterone effects on dendritic morphology.
Repeated daily restraint stress and daily corticosterone administration to adult male Sprague-Dawley rats leads to decreases in the number of branch points and length of dendrites of CA3 pyramidal neurons of the hippocampal formation. This decrease is prevented by daily administration of the antiepileptic drug phenytoin (Dilantin), which is known to interfere with excitatory amino acid release and actions. Phenytoin had no obvious effect on behavior during and after stress and failed to prevent stress-induced reduction of body weight gain and stress-induced increases of adrenal weight relative to body weight; it also failed to attenuate glucocorticoid-induced diminution of the size of the thymus gland, indicating that it does not directly antagonize glucocorticoid actions. Stress- and corticosterone-induced effects on dendritic length and branch point number are more pronounced on the apical, as opposed to the basal, CA3 dendrites that receive the largest mossy fiber input from the dentate gyrus. Because phenytoin is also known to prevent ischemic damage, these results are consistent with a model in which stress- and corticosterone-induced CA3 dendritic atrophy is produced by excitatory amino acids released from the mossy fibers.
The rat dentate gyrus is unusual among mammalian brain regions in that it shows cell birth well into adulthood. During development, dentate gyrus cell birth is regulated by adrenal steroids. However, it is presently unknown whether cell division in the adult is also mediated by these same factors. In order to determine whether this is the case, we combined adrenalectomy, with or without corticosterone (CORT) replacement, and 3H-thymidine autoradiography, Nissl staining, and immunohistochemistry for the glial cell markers vimentin and glial fibrillary acidic protein (GFAP) as well as for the neuronal marker neuron-specific enolase. Removal of circulating adrenal steroids resulted in a greater density of both GFAP-immunoreactive and vimentin-immunoreactive cells compared to sham-operated animals; CORT replacement prevented increases in both of these cell types. The increase in the density of vimentin-immunoreactive cells probably resulted from an increase in the birth of these cells, as adrenalectomized rats showed greater numbers of 3H-thymidine-labeled vimentin-positive cells compared to sham rats. In contrast, no changes in the number of 3H-thymidine-labeled GFAP-positive cells were observed with adrenalectomy, indicating that the increase in this cell type probably does not involve cell birth. In addition, the density of 3H-thymidine-labeled cells that were not immunoreactive for either glial cell marker and that showed neuronal characteristics was dramatically increased with adrenalectomy. These results suggest that adrenal hormones normally suppress the birth of both glia and neurons in the adult rat dentate gyrus.
Unlike the majority of mammalian brain regions, the rat dentate gyrus undergoes maximal cell birth and cell death during the same developmental time period. Granule cell birth and death peak at the end of the first postnatal week. We have found that manipulations of glucocorticoid levels during the stress hyporesponsive period profoundly influence the density of pyknotic cells in the dentate gyrus while apparently not affecting the density of healthy cells. This raises the possibility that glucocorticoids are regulating processes in addition to cell death, i.e., cell birth. In order to determine whether increases in circulating glucocorticoids or mineralocorticoids affect the birth of cells in the developing dentate gyrus, 3H-thymidine autoradiography was performed on brains of rat pups treated with either corticosterone or aldosterone during the first postnatal week. Quantitative analysis of 3H-thymidine-labelled cells revealed significant decreases in the density of labelled cells in the granule cell layers with both corticosterone and aldosterone treatment. In these same brains, significant decreases in the density of pyknotic cells were also observed in the granule cell layers. However, no changes in the numbers of 3H-thymidine-labelled pyknotic cells were observed with any treatment. Increases in circulating corticosterone or aldosterone resulted in significant increases in the density of both 3H-thymidine-labelled and pyknotic cells in the hilus. These results suggest that dentate gyrus cell birth and cell death are related and that these processes are regulated by adrenal steroids.
To evaluate extracellular hydrolytic enzymes in an in vivo system, plastic chambers were glued over rabbit dermal BCG lesions in various stages of development, after the central epithelium was removed with a scalpel. They were filled with tissue culture medium and left in place 2 days. The following enzymes in the fluid were assayed: collagenase (an enzyme secreted but not stored in macrophages); lysozyme (both secreted and stored); DNase and RNase (released on cell death and possibly regurgitated but not secreted); and, as a control, lactic dehydrogenase (released only on cell death). Tissue sections were prepared and studied histologically for the type of cell infiltrate, for beta-galactosidase (our marker enzyme for macrophage activation), and for necrosis. At 11 and 18 days of age the BCG lesions were largest and the number of activated macrophages in the chamber beds was highest. At this time the levels of the five enzymes assayed in the chamber fluids reached their peaks, tuberculin hypersensitivity was well developed, and the bacilli components would still be plentiful. In general, the chamber fluids from 11- and 18-day BCG lesions contained higher enzyme levels than chamber fluids from tuberculin reactions. Active collagenase was only detected in fluids from such BCG lesions. Evidently, the serum in the chamber fluids was sufficient to inhibit the lower amounts of collagenase probably released from smaller BCG lesions and tuberculin reactions (and from the 2-week polystyrene lesions that were also evaluated). These studies demonstrate that in chronic inflammatory reactions, both acid-acting and neutral-acting hydrolytic enzymes are released extracellularly. Tissue components would be hydrolyzed locally wherever the acid-acting hydrolytic enzymes encounter a drop in pH and wherever the concentration of neutral-acting hydrolytic enzymes exceeds the concentration of their inhibitors.