Adrenalectomy decreases nerve growth factor in young adult rat hippocampus.

Abstract

The effect of adrenalectomy on the level of nerve growth factor (NGF) in the hippocampus and on the distribution of choline acetyltransferase i ureactivity in forebrain cholinergic neurons of developing rats was studied. Biological and immunohistochemical determinations indicated that in 40-day-old rats, adrenalectomy reduced the NGF level in the hippocampus and the choline acetyltrsferase immunoreactivity in the septal lateral bands. Furthermore, autoradiographic studies showed that adrenalectomy causes changes in the distribution and expression of NGF receptors in the hippocampus. These results suggest that adrenal hormones are involved in the regulation of the NGF level in the hippocampus and of NGF receptors in the septum.Nerve growth factor (NGF) is a polypeptide found in both the peripheral (1) and the central (2) nervous system. In the rat central nervous system, the hippocampus contains one of the highest levels of NGF and of mRNA encoding NGF (2-5). Several lines of evidence indicate that NGF is synthesized within the hippocampus, taken up selectively by cholinergic neurons of the septal lateral band (SLB) terminals, and transported retrogradely to the cell of origin (6-9). Intrahippocampal injection of NGF antibodies causes granule cell loss (10), further suggesting that NGF plays a physiological role in the central nervous system. The hippocampus is a major target site of glucocorticoid hormones, particularly corticosterone, and administration ofglucocorticoids early in development influences brain and somatic growth (11). Furthermore, recent in vitro and in vivo studies have shown that glucocorticoids have a profound influence on the survival of hippocampal neurons (12). Whether or not these hormonal activities affect the level of NGF in the hippocampus and the distribution of NGF receptors in the basal forebrain cholinergic neurons has yet to be explored. The present studies show that in developing rats, adrenalectomy significantly reduces the level of NGF in the hippocampus and of choline acetyltransferase (ChAT) immunoreactivity in the cholinergic neurons of the SLB while enhancing a concomitant increase of NGF receptor expression in the septal neurons. A preliminary account of these studies has been presented.* MATERIALS AND METHODSAnimals and Adrenalectomy. Forty-day-old SpragueDawley rats (90-100 g) were purchased from Nossan (Calco, Italy). Rats were subjected either to bilateral adrenalectomy or to sham operation (laparotomy) under ether anesthesia. Corticosterone (Sigma) was dissolved in ethanol/saline, 1:9 (vol/vol), and injected intradermally into the adrenalectomized (Adx) rats at doses of 2 gg every other day for 2 weeks. Adx rats were given 0.9% NaCl in place of drinking water to compensate for the loss of salt.Mouse NGF (2.5S) was purified from male mouse submaxillary glands (13). Polyclonal NGF antibodies were prepared (14,15) and purified by affinity chromatography (16).Biological Assays. At intervals, control and treated rats were killed with an overdose of ether vapor and ...

Neurotrophic Activity in Embryonic Chick Brain: Early Appearance and Differential Regional Distribution

“…Thus, the source of these differences is unclear and must remain the object of addi tional investigation. The fact that the activity found in the HCX was not generally greater than that found in the remaining forebrain tissue is in contrast to observations made in the mammalian species, in which the hippocam pus has been demonstrated to contain particularly high levels of both well-characterized factors (e.g., NGF, bFGF [24,25]) and uncharacterized substances [1]. This is not necessarily unexpected, since the homology of the avian and mammalian hippocampal formation has not been well established, although there are some similari ties in afferent and efferent connectivity [26].…”

The expanding role of nerve growth factor: from neurotrophic activity to immunologic diseases

“…Tlie hypothesis of a role of NGF in the endocrine system is supported by evidence that NGF is present in the hypophysis and hypothalamus (56,57), and that thyroid and adrenal hormones are strong promoters of NGF synthesis (58,59). Moreover, the administration of NGF antibodies into rat fetuses inhibits the availabihty and activity of endogenous NGF, inducing a significant loss in body growth and a marked neuroendocrine deficit in offspring (60).…”

Haloperidol Administration in Humans Lowers Plasma Nerve Growth Factor Level: Evidence that Sedation Induces Opposite Effects to Arousal

“…24, 25], Since adrenal gland hormones are known to play a regulatory role in the synthesis of NGF [24], and NGF exerts a stimulatory effect on the hypotha lamic-pituitary-adrenal axis [26], it is also possible that HA acts through these types of endocrine mechanisms. Interestingly, recent reports indicate that alteration of neurotrophin-3 gene polymorphism seems to be associat ed with schizophrenia [27], A relevant question raised by the present observations is whether the effect of HA is mediated by peripheral or central mechanisms and, more importantly, whether the circulating NGF in patients treated with HA reaches and/ or influences NGF-receptive cells in the CNS.…”