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Biomedical subjects

I A Hendry

Publications and source records attributed to I A Hendry.

At least 91 records · Page 5Linked to original sources

Development of sympathetic neurones in vivo: an investigation of the possible role of glucocorticosteroids in regulating transmitter type.

In vivo the majority of sympathetic neurones are adrenergic, whereas in vitro they can become cholinergic. This atypical cholinergic development can be suppressed by addition of a glucocorticoid to the culture medium (McLennan, Hill and Hendry, 1980). In this paper we have investigated the possibility that glucocorticoids influence the choice of sympathetic transmitter type in vivo. Reduction in circulatory glucocorticoids by adrenalectomy of 2-day-old rat pups did not result in increased cholinergic development in their superior cervical ganglia. Furthermore, administration of exogenous corticosterone to increase circulatory glucocorticoids in young rats did not prevent the developmental switch in transmitter type of the sympathetic innervation of the sweat gland from adrenergic to cholinergic. It is concluded that the developmental regulation of sympathetic transmitter type in vitro may not be analogous to that in vivo.

Adrenal Glands↗

Pharmacology of the steroid regulation of transmitter choice in cultured rat sympathetic ganglia.

The normally adrenergic rat superior cervical ganglion becomes cholinergic when grown in explant culture. This response is prevented by the physiological glucocorticosteroid, corticosterone, and the mineralocorticoid, aldosterone. The synthetic glucocorticosteroid, RU 26988, was also active in this respect. Progesterone, spironolactone, testosterone and 17 beta-estradiol were all inactive at 10(-6) M, demonstrating the specificity of the response. The response to 10(-7) M corticosterone was not antagonized by a hundred-fold excess of progesterone, testosterone, cortexolone or spironolactone. The response to 10(-7) M aldosterone was antagonized by spironolactone but not by progesterone. The order of potency of the agonists in this study is similar to that described for classical glucocorticoid receptors. The action of aldosterone was antagonized, however, by the mineralocorticoid antagonist, spironolactone. Thus, the steroid response described here may be mediated by both glucocorticoid and mineralocorticoid receptors or, alternatively, by a new glucocorticoid receptor which can be antagonized by a mineralocorticoid antagonist.

Aldosterone↗

Reversible dissociation of a bovine cardiac factor that supports survival of avian ciliary ganglionic neurones.

The relationship has been studied between a high and a low molecular weight form of a bovine cardiac factor that supports the survival of avian ciliary ganglionic neurones in culture. Reversible dissociation of the high molecular weight form into identical or similarly sized subunits of apparent molecular weight in the range 15,000-30,000 has been demonstrated. In addition, other inactive high molecular weight components of cardiac extract were found to interact synergistically with both active forms of the factor.

Animals↗

Interactions between developing autonomic neurons and their target tissues.

Neurons critically depend on contact with the correct target tissue in order to survive and mature. The number of neurons surviving in a nerve centre directly depends on the size of the peripheral field in innervates. It has been proposed that target tissues release a neurotrophic substance (retrophin) which is internalized by nerve terminals and retrogradely transported to the perikarya where its action results in the survival of appropriate neurons. In the sympathetic nervous system, nerve growth factor probably acts as a retrophin. Similar retrophins must exist for other neuronal systems. In order to identify a parasympathetic retrophin two approaches have been taken. One was to grow appropriate target tissues with radiolabelled amino acids and to determine whether the proteins synthesized and released by these target tissues were retrogradely transported by parasympathetic neurons in vivo. The other approach was to show that a purified neurotrophic factor for the chick ciliary ganglion could be retrogradely transported by parasympathetic neurons. The results have suggested that at least two retrophins are involved in the normal development of the autonomic nervous system: one, nerve growth factor, for the sympathetic nervous system and the other, as yet unnamed, for the parasympathetic system.

Afferent Pathways↗

Effect of peripheral deprivation on mammalian motoneurone development.

Foetal rat hindlimbs were removed at 18 days gestation to determine the effect of target tissue removal on the development of mammalian motoneurones. At 25 days postnatal there was a large reduction in the numbers of motoneurones with a corresponding drop in the activity of choline acetyltransferase as well as in the total protein content on the ipsilateral side of the spinal cord. These results show that in mammals, as in other vertebrates, the size of a neuronal population is regulated by the size of the peripheral field innervated.

Animals↗

Retrogradely transported nerve growth factor increases ornithine decarboxylase activity in rat superior cervical ganglia.

Nerve growth factor (NGF) transported intraaxonally from the adrenergic nerve terminals in the iris to the cell bodies in the superior cervical ganglion resulted in an increase in the activity of the enzyme ornithine decarboxylase in the ganglion. This occurred in both six-day-old and adult rats with the relative effect of the retrogradely transported NGF being greater in adult animals. These results suggest that the induction of ornithine decarboxylase by NGF may be due to the stimulation of intracellular receptors.

Aging↗

Denervation-induced decreases in enzyme activity of rat superior cervical ganglia differ in vivo and in vitro.

The decrease in tyrosine hydroxylase activity following denervation in vivo and subsequent culture in vitro was examined to determine the role of the preganglionic nerve in this decrease. Ganglia denervated in vivo prior to culture showed a greater decrease than ganglia maintained for the same total period in vitro, and hence denervated for the same time, suggesting factors in addition to the loss of the preganglionic nerve are involved in vivo.

Aging↗

Retrograde axonal transport of target tissue-derived macromolecules.

Neurones depend on contact with their target tissues for survival and subsequent development. The protein, nerve growth factor (NGF), can be selectively taken up by sympathetic nerve terminals and reaches the neuronal perikaryon by a process of retrograde intra-axonal transport, suggesting that its role in vivo is to act as a target tissue-derived trophic factor. The development of the neurones of the chick ciliary ganglion requires the presence of structures derived from the optic cup. Several studies in vitro have shown that media conditioned by non-neuronal cells contain factors that result in the survival of neurones from ciliary ganglia. In particular, chick embryo iris, ciliary body and choroid contained large amounts of these factors indicating the presence of a target tissue-derived trophic factor for the cholinergic ciliary ganglion. This study demonstrates that neurones of the ciliary ganglion accumulate, by retrograde intra-axonal transport, proteins synthesized and released by optic tissues in culture.

Animals↗

Characterization of a cardiac muscle factor required for the survival of cultured parasympathetic neurones.

A macromolecule from ox cardiac muscle which supports the survival of dissociated embryonic chick ciliary ganglionic neurones in culture has been partially purified and characterized. Gel filtration after ammonium sulphate fractionation separated two peaks of activity, a high molecular weight form (greater than 50,000) which dissociated to a lower molecular weight component (approximately 20,000). The high molecular weight form was retained by DEAE-cellulose at neutral pH and was eluted by 0.11-0.16 M NaCl. The isoelectric point of the factor was 6.2.

Animals↗

Influence of cardiac extracts on cultured ciliary ganglia.

Inclusion of extracts of rat hearts in culture medium resulted in both a fibre outgrowth and maintenance of choline acetyltransferase (CAT) activity in explained chicken embryo ciliary ganglia. CAT activity was maintained in ganglia from 7- to 19-day-old embryos whereas fibre outgrowth was maximal in ganglia from 8- to 11-day-old embryos and as the embryo matured ganglia became less responsive, showing virtually no fibre response by 16 days. The fibre outgrowth response had an absolute dependence on serum in the medium and a pH optimum of 7.1--7.3. Maintenance of CAT was stimulated by, but not absolutely dependent on, the presence of serum in the medium and was insensitive to changes in the pH of the culture medium between 7.2 and 8.0 but was sensitive to decreases in pH below 7.2. Horse and fetal calf serum were equally effective in stimulating the cardiac extract medium-induced maintenance of CAT activity and induction of fibre outgrowth.

Animals↗

The influence of preganglionic nerves on the superior cervical ganglion of the rat.

Sympathetic neurones grown in tissue culture with non-neuronal cells become cholinergic. Such a change from an adrenergic to cholinergic character does not occur in vivo and it has been suggested that this may be due to the determination of the adrenergic character by electrical activity. Electrical activity in the superior cervical ganglion by young rats were prevented by transection of the preganglionic nerve trunk. In no case did this operation result in an increase in the intrinsic choline acetyltransferase (CAT) of the ganglion. We conclude that electrical activity is not the factor responsible for the difference between in vivo and in vitro results.

Adrenergic Fibers↗