Showing papers by "Bruce S. McEwen published in 1970"

Selective retention of oestradiol by cell nuclei in specific brain regions of the ovariectomized rat.

Abstract: —Cell nuclei were isolated from four regions of the brains of ovariectomized female rats 2 hr after the injection of [3H]oestradiol. By light microscopy, the nuclear pellets contained highly purified nuclei of neuronal and glial cells with little cytoplasmic contamination. Tritium was concentrated in cell nuclei from the preoptic-hypothalamic area, to a lesser extent in nuclei from the amygdaloid region and hippocampus, and least of all in cerebral cortical nuclei. In comparison with whole homogenates (= 1-0), the nuclear concentrations of radioactivity were 12·9, 4·7, 1·9 and 0·8, respectively. Approximately 40 per cent of the radioactivity in homogenates of the preoptic-hypothalamic area was present in cell nuclei, and upon TLC more than 85 per cent of the radioactive material in the nuclei exhibited the RF of oestradiol-17β. Pretreatment of ovariectomized females with 1 mg of unlabelled oestradiol 30 min before the injection of labelled hormone abolished the nuclear uptake of [3H]oestradiol in all four regions of the brain. A concurrent injection of 10 μg of unlabelled oestradiol-17β significantly reduced nuclear uptake, while a similar injection of testosterone or oestradiol-17α had no significant effect. One mg of oestradiol-17α, but not testosterone, did reduce nuclear uptake. The retention of [3H]oestradiol by the preoptic-hypothalamic area decreased exponentially in the tissue from 30 min to 4 h after an intraperitoneal injection; however, nuclear binding reached a peak at 1-2 h and still showed high retention at 4 h. These results, together with observations in other laboratories of morphological changes induced by oestrogens, establish that certain regions of the brain are bona fide targets for the action of oestradiol.

Amnesia produced by electroconvulsive shock or cycloheximide: conditions for recovery.

Abstract: Retrograde amnesia for a passive avoidance response was produced in rats by electroconvulsive shock and in mice by cycloheximide, an inhibitor of protein synthesis. One day after training the memory could be restored if a "reminder" of the original foot shock was given after the retention test on which the amnesia was demonstrated. Memory did not return if the reminder was given without the prior retention test or if the reminder and the test were separated by 23 hours.

Temporal characteristics of amnesia induced by protein synthesis inhibitor: determination by shock level.

Abstract: IT is widely accepted that cerebral protein synthesis is involved in “long term” but not “short term” memory. Evidence for this comes from experiments in which amnesia for a multiple-trial avoidance task is induced by administration of protein synthesis inhibitors before or shortly after training1–3. In mice4–6, the amnesia, which is permanent, does not appear until 3 h or more after training, leading to the notion of a “short term” memory, and is not produced if the criterion for learning is too severe. We have given mice a different learning task and used the protein synthesis inhibitor cycloheximide to induce amnesia that has such different characteristics as to warrant a re-evaluation of the hypothesis.

Axonal Transport of Neurotubule Protein

Abstract: IT has been known for some time that there is a constant somatofugal transport of materials down axons1, but it has only recently been clearly demonstrated that more than one rate of transport may exist, and that transport cannot therefore be considered to be a single process2–4. As far as transport of protein is concerned, at least two mechanisms seem to be operating, at significantly different rates. First, there is a “fast” protein component, which, as our previous studies have shown, advances at a rate of about 50 mm per day in goldfish optic nerve5; its counterpart in mammalian nerve has been found to have a rate of up to about 500 mm per day6,7. Second, there is a “slow” component whose rate of advance is about two orders of magnitude slower; the value in goldfish optic nerve was found to be about 0.4 mm/day (ref. 8), while in mammalian nerve, values of 1–10 mm per day have been observed2. It is clear, moreover, that the fast and slow types of transport involve different cellular constituents, for the fast component consists almost entirely of insoluble—that is, particulate—protein, while the slow component contains about 40–50 per cent soluble protein5,9.

Association of 3H corticosterone-1,2 with macromolecules extracted from brain cell nuclei.

Abstract: CORTICOSTERONE, the principal adrenal steroid in the rat,, is retained by cell nuclei in the brain of adrenalectomized rats by a process specific to the corticosterone structure1. Nuclear binding of hormone is greatest in the hippocampus, where we have previously found the highest tissue concentration of radioactive hormone, but is also significant throughout the rest of the brain1,2. The binding of steroid hormone to cell nuclei in other target tissues, indicates that the hormone receptor is protein which can be extracted from the nuclei by moderate salt concentrations3–6. We now present evidence that hormone within brain cell nuclei is bound to a macromolecular component, probably protein, which can be extracted from isolated nuclei by 0.4 M NaCl.

The uptake and action of corticosterone: regional and subcellular studies on rat brain.

Abstract: Publisher Summary This chapter discusses a general conceptual framework within which behavioral effects of corticosterone can be recognized and studied The primary requirement for the brain to act as a sensing device for the regulation of adrenocorticotropic hormone (ACTH) secretion and as a target organ for corticosterone to influence neural activity and behavior is that the hormone be able to enter the brain in increasing amounts as the blood level increases, as it does in stress This chapter focuses on the physiological and behavioral consequences of corticosterone action on the hippocampus and other regions of the brain There is a growing body of evidence that indicates that adrenal steroids act directly on the brain to regulate release of ACTH from the pituitary and to moderate neural activity underlying behavioral responses Lesion and electrical stimulation studies of the limbic system indicate that the hippocampus, as part of a delicately counterbalanced system of excitation and inhibition converging on the median eminence (ME), has an inhibitory influence on ACTH release

Steroid Hormone Interaction with Specific Brain Regions

Abstract: One aim of the burgeoning field of neurobiology is to elucidate the role of basic cellular mechanisms common to all cell types in the neural control of behavior and of endocrine and other vegetative functions. This is a formidable task, considering the enormous complexity of the brain and there is no one single approach which will provide all the answers. In fact, the diversity of disciplines and research strategies, some of which are represented in this symposium, is one of the attractive features of the field. We have chosen to focus on the role of the cell nucleus in the regulation of cellular events in the brain, since this organelle contains the genetic information from which virtually all cellular processes ultimately take their form. We have also chosen to examine the action of steroid hormones on brain biochemistry, since there are at least two good reasons for this choice related to our interest in brain cell nuclei.