Oxytocin neurones are recruited into co-ordinated fluctuations of firing before bursting in the rat.

Hypothalamic oxytocin neurones have dual physiological functions with associated characteristic activity patterns: a homeostatic osmoregulatory role involving continuous low frequency firing at a relatively constant rate, and roles associated with reproduction involving periodic, brief, synchronised, high frequency bursts of spikes. Apparently the same neurones maintain both roles during reproduction, when both activity patterns occur simultaneously, although sometimes factors linked to the homeostatic response predominate and prevent bursting. With the object of understanding how oxytocin neuronal networks manage both roles during lactation, we analysed basal activity between bursts in simultaneously recorded neurones to reveal potentially adaptive changes in network behaviour. Negative autocorrelation on a time scale of 0.5-2 s occurs in basal activity between bursts but also in non-bursting oxytocin neurones, and can therefore be associated with the system's homeostatic role. Although the system responds to the pups suckling by the induction of bursting, there are also increasing fluctuations in firing that are positively correlated in some simultaneously recorded neurones during basal activity between bursts. A few seconds before bursts, cross-correlation strengthens, irregularity of firing increases, and serial correlation (autocorrelation) weakens, all substantially. After pharmacological treatments known to facilitate bursting, cross-correlation and irregularity of firing increase and autocorrelation weakens, and the reverse occurs in conditions that delay bursting (hyperosmotic stress and pharmacological interventions). Our analyses suggest heterogeneity in the population of oxytocin neurones during lactation; the range including 'leader neurones' that readily display co-ordinated fluctuations in firing in response to suckling and escape from negative autocorrelation just before bursts, and 'follower neurones' that fire at a relatively constant rate in no apparent relationship to others, except when recruited late to bursting, probably in response to massive stimulation from already bursting neurones. The steep increases in correlation a few seconds before bursts reflect an accelerating process of recruitment of follower neurones to co-ordinated fluctuations, leading to the phase transition that constitutes the critical stage of burst generation.

Glucocorticoids up-regulate the expression of glial fibrillary acidic protein in the rat suprachiasmatic nucleus.

Immunoreactivity against glial fibrillary acidic protein (GFAP) was used as a dynamic index in adrenalectomized rats subjected or not to corticosterone replacement to investigate whether glucocorticoids may interact with astrocytes in the suprachiasmatic nucleus (SCN), the master component of the central circadian clock. GFAP staining in the SCN was significantly higher in rats having received implants that restored physiological plasma levels of corticosterone within diurnal or nocturnal limits than in non-normalized rats. The effects of corticosterone were similar in the parvocellular portion of the paraventricular nucleus but were opposite in the hippocampus, another major site of negative feed-back regulation of the hypothalamic-pituitary-adrenal axis, where a decreased GFAP staining was observed in discrete regions of the dentate gyrus. This indicates that glucocorticoids may positively or negatively regulate GFAP, depending on the target brain structure. In the SCN, that contains only few if any glucocorticoid receptors, indirect mechanisms that may involve serotoninergic neurons are probably responsible for the effects of corticosterone level. It is proposed that the corticosterone-induced increase in GFAP staining in that nucleus accounts for dynamic changes in neurone-astrocyte interactions that might occur in relation with natural fluctuations of glucocorticoids over the 24 h period.

Effects of bilateral olfactory bulbectomy on circadian rhythms of ACTH, corticosterone, motor activity and body temperature in male rats.

Bilateral olfactory bulbectomy (BOX) has major biochemical and behavioral effects, and is one of the most widely investigated of animal models of depression. We studied the consequences of BOX in male rats, on the organization of endogenous circadian rhythms for ACTH, corticosterone (Cort), motor activity (MA) and body temperature (BT). Mean levels were increased for Cort and MA, whereas no significant changes were observed for ACTH and BT. Significantly higher plasma Cort morning values were evidenced in BOX than sham-operated animals. In addition, compared with the single prominent power spectrum for the 24 hours period of control rats, the BOX animals displayed substantially lower 24 hours spectral power for the MA and BT circadian rhythms. These alterations suggest that olfactory bulbectomy, by disruption of the afferences and efferences, induced drastic changes in the function of the endogenous clock or of its regulating systems. From this point of view, bulbectomized rats may therefore be a valuable model to studying the etiology of psychiatric disorders with rhythm disturbance.

Effects of acute tilt from orthostatic to head-down antiorthostatic restraint and of sustained restraint on the intra-cerebroventricular pressure in rats.

The tail-cast suspension rat model was developed to explore in ground laboratories the physiological effects of some of the stresses prevailing during space flight including and among them those of the headwards body fluid shifts. We recently showed in rats that an acute head-down tilt (45 degrees) from tail-cast orthostatic (OR) to antiorthostatic restraint (AOR) induced within 30 min and for 2 to 4 h an acute stress-like surge in plasma ACTH and corticosterone levels. Considering the proximity of the CRF producing neurons with the 3rd ventricle, we decided to explore the acute and longer-term effects of the OR/AOR tilt on the intra-cerebroventricular pressure (Picv) measured with an indwelling sensor-transmitter catheter stereotaxically implanted in the 3rd ventricle. At 1- or 10-min intervals the unit sent radiotelemetric signals for both Picv and motor activity (MA) to a receiver coupled with an automatic data analyser. The acute AOR-tilt induced within 10 min and for 60 min a 2.5-fold rise in Picv which receded to baseline between 60 and 90 min. During this time, the normally close correlation between Picv and MA was lost, as assessed by Spearman's rank coefficient. In a long-term experimental series we explored the evolution of both Picv and MA in individual rats subjected successively to a 7 day control phase (C). 7 days OR, and 3 days AOR. After the 1-h-long post-tilt rise of the Picv, the mean Picv levels measured for the next 3 days decreased significantly vs. both the preceding OR phase (-30%) and the initial C Phase (-40%). The circadian pattern of the diurnal Picv profile was impaired, as evidenced by a significant fall (i) in the night/day ratio (-25% vs. C). and (ii) even more in the spectral power of the circadian 1 c/24 h frequency (-85% vs. C). The simultaneously recorded MA fluctuations similarly displayed an altered diurnal pattern with a spectral power of the circadian frequency reduced to 7% of controls. However, contrary to the short-term experiment, in the long-term study the large alterations to both Picv and MA were strongly correlated, as during the control phase. The mechanisms involved in the swift post-tilt rise in the Picv together with an aroused corticotropic axis, and in the impact of sustained head-down restraint on CNS-controlled adaptive regulations including their circadian rhythms remain unknown.

A role for bursa fabricii and bursin in the ontogeny of the pineal biosynthetic activity in the chicken.

The tripeptide bursin (Lys-His-Gly-NH2) is a B cell differentiation hormone derived from the bursa fabricii. The latter is a cloacal diverticulum and the site of B lymphocyte differentiation and selection in aves; also the bursa fabricii is involved in endocrine functions. Herein we demonstrate that in the chicken, the bursa fabricii and bursin are crucial to the ontogeny of both the pineal response to antigenic challenge and pineal circadian synthetic activity. In early embryonically bursectomized chickens, the plasma melatonin response to immunization by porcine thyroglobulin (Tg) was abolished. Also, the amplitudes of both plasma melatonin and pineal N-acetyltransferase (NAT) circadian rhythms were reduced by 50%, whereas the activity of hydroxyindole-O-methyltransferase (HIOMT) remained unchanged. Conversely, administration of either minute amounts (100 pg, 100 fg) or highly dilute (5 x 10(-27) g) bursin, with the exception of a highest dose (100 micrograms), to bursaless embryos induced recovery of normal antigen-induced melatonin response and normal amplitudes of melatonin and NAT rhythms. These findings establish that early in embryonic life, the bursa fabricii and its derived signal (bursin) are essential for normal development of pineal synthetic activity and underline the efficacy of very dilute bursin as an informative signal.

Involvement of central histamine in the early phase of ACTH and corticosterone responses to endotoxin in rats.

The involvement of histaminergic transmission in the rapid and sustained plasma ACTH and corticosterone (CORT) responses induced in conscious rats by intra-arterial infusions of 25 micrograms.kg-1 Escherichia coli lipopolysaccharide (LPS) was investigated. LPS challenge produced a rapid and transient increase (+ 62%) in the amount of histamine (HA) in the median eminence 15 min after LPS administration, which contrasted with constant concentrations of plasma HA throughout the entire study (up to 480 min). Blockade of histaminergic receptors by intra-arterial pretreatment with H1 or H2 antagonists (mepyramine, 1 mg/rat, and cimetidine, 2 mg/rat), administered separately, did not affect either ACTH or CORT responses to LPS. Pretreatment with the same doses of the two antagonists in combination very significantly but transiently impaired the earliest phase (30 min) of the ACTH and CORT responses, without any apparent effect on the late phase of these responses. Pretreatment of the animals with an H3-receptor agonist (R alpha-methylhistamine dihydrochloride, 1 mg/rat) similarly blunted the early corticotropic responses to LPS, and also slightly depressed the long-lasting CORT response. These findings support the view that activated central HA transmission may be a key intermediate mechanism triggering the CRH41-ACTH-CORT responses to LPS, in addition to the previously demonstrated activating role of catecholaminergic afferences to the CRH41 neurons during this early complex phase of corticotropic response to LPS.

Different responses of plasma ACTH and corticosterone and of plasma interleukin-1 beta to single and recurrent endotoxin challenges.

In a parallel study in 10 individual rats, three time series of plasma concentrations of ACTH, corticosterone (CORT), and interleukin-1 beta (IL-1 beta) were measured before (time 0) and at intervals between 15 and 480 min following intra-arterial (i.a.) infusions of 25 microgram/kg lipopolysaccharide (LPS). All LPS injections were given at 9 AM. The first time series was performed on naive rats (day 1). A sequence of six daily injections (days 3-8) of the same dose of LPS followed. The post-LPS time course of the plasma ACTH, CORT and IL-1 beta levels were studies on days 3 (second injection) and 8 (seventh injection). The first LPS injection induced a rapid (30 min) eightfold rise in plasma ACTH and CORT, culminating in concentrations 30 times the baseline at 60 min (ACTH) and 15 times baseline at 120 min (CORT). Both hormones receded back to the initial basal level at 480 min. On the other hand, IL-1 beta increased slowly to peak at 13 times baseline 120 min before declining to minimal seven- to ninefold basal levels, 480 min and even 48 h post-LPS. During the second phase of the experiment starting 48 h after the initial LPS priming sequence, the ACTH and CORT responses to daily recurrent LPS injections again differed from those of IL-1 beta. The post-LPS time courses of the ACTH and CORT reaction displayed a typical pattern of a progressive attenuation studied at days 3 and 8. The peak amplitudes at days 3 and 8 were reduced to 60 and 10%, respectively, for ACTH, and to 85 and 45% for CORT of those observed at the first LPS test. The duration of the response (both) was also shortened from 480 min (first LPS test) to 300 min at days 3 and 8. The post-LPS patterns of the IL-1 beta responses were characterized, first by basal levels seven to nine times higher than the initial baseline values (day 1), and by a rapid suppression of the post-LPS response, with only a slight (30%) increase at day 3 and no increase at day 8. Thus, after both acute and recurrent LPS administration, ACTH/CORT and IL-1 beta reacted differently to the endotoxin challenge. The two LPS reactive systems were not correlated. This is inconsistent with the often proposed role of increased plasma IL-1 beta release as an intermediary factor in the LPS-induced recruitment of the corticotropic axis in general infections.

Early hypothalamic activation of combined Fos and CRH41 immunoreactivity and of CRH41 release in push-pull cannulated rats after systemic endotoxin challenge.

We previously showed that intra-arterial endotoxin infusion (lipopolysaccharide [LPS]: 25 micrograms.kg-1) induced an early (15 min) and sustained (480 min) rise in plasma ACTH associated with delayed (60-120 min) increases in plasma concentrations of TNF alpha, IL-6, and IL-1 beta. In the present study, we followed the post-LPS time-course of immunocytochemical expression of Fos-like activity in CRH41 neurons whose immunolabeling was enhanced by icv colchicine pretreatment 48 h before the LPS, and CRH41 release in the push-pull cannulated median eminence of free-moving rats, in parallel with the ACTH response. The earliest Fos-like activity in IR-CHR41 neurons was detected 30 min post-LPS. Colchicine strongly inhibited the LPS-induced activation of Fos expression in single-labeled paraventricular neurons. CRH41 release in the median eminence displayed a biphasic stimulation pattern, with a first peak (+60%) at 15 min together with the ACTH surge, followed by a second rise beginning at 45 min and lasting more than 2 h. Thus, the early stage of the ACTH surge following a nonlethal endotoxin challenge (< 60 min) already involves the activation of CRH41-producing neurons.

Chronic orthostatic and antiorthostatic restraint induce neuroendocrine, immune and neurophysiologial disorders in rats.

The tail-cast suspension rat model has been developed in ground laboratories interested in space physiology for extensive study of mechanisms causing the pathophysiological syndrome associated with space flights. We used individually-caged male rats to explore the effects of acute and chronic (7d) orthostatic restraint (OR) and head-down anti-orthostatic restraint (AOR) on a series of physiological variables. The acute restraint study showed that (1) the installation of the OR device induced an acute reaction for 2 days, with a substantial rise in ACTH (x2) and CORT (x6), and that (2) the head-down tilt from OR to AOR induced (i) within 10 min and lasting 60 min a 2-fold rise in the intra-cerebro-ventricular pressure (Picv) monitored with an icv telemetric recording system, which receded to normal between 60 and 120 min; and (ii) within 30 min a short-lived 4-fold rise in plasma ACTH and CORT levels. Chronic OR induced (1) the suppression of the diurnal ACTH/CORT rhythm, with increased mean levels, especially for ACTH, (2) a degraded circadian locomotor activity rhythm manifested by a significant reduction in the spectral power of the 24h periodicity and a concomitant emergence of shorter (ultradian) periodicities, (3) an associated, but less pronounced alteration of the diurnal rhythm in body temperature; and (4) a marked increase in baseline plasma levels of IL-1 beta and an increased reactivity in cytokine release following an E. coli endotoxin (LPS) challenge. AOR induced (1) a similar obliteration of the circadian ACTH/CORT rhythm, (2) the loss of close correlation between ACTH and CORT, (3) a generalized increase in baseline plasma IL-1 beta levels and (4) more extensive degradation of the circadian periodicity for both locomotor activity and, to a lesser extent, body temperature, replaced by dominant spectral powers for ultradian periodicities (3 to 10h). In conclusion, both experimental paradigms--but AOR more than OR--caused a blockade of the circadian rhythmicity of major physiological variables, the loss of normal correlations between ACTH and CORT, and inflammatory-immune hyperreactivity. These pathophysiological disorders may all be parts of a complex chronic stress syndrome.

[The corticotropic axis response after subcutaneous endotoxin injection is not associated with the increase of plasma interleukin-1 beta]. / La réponse de l'axe corticotrope à l'injection sous-cutanée d'endotoxine n'est pas associée à une élévation de l'Interleukine-1 beta plasmatique.

When injected through an intra-arterial (i. a.) cannula, LPS induced a rapid (15-30 min) and long-lasting (> 300 min) increase in plasma ACTH and corticosterone (CORT) levels. The duration of these responses depended on the LPS dose, and except for very small LPS doses, their amplitudes appeared independent of the dose of endotoxin. ACTH peaks (2,200 pg.ml-1) occurred between 30 and 120 min, whereas CORT always reached maximal levels at 120 min. Plasma Interleukin-1 beta (IL-1 beta) levels were always undetectable during the early phase of corticotropic stimulation, but increased strikingly 120 min after LPS injection. Increasing LPS doses, resulted in enhanced and prolonged IL-1 beta plasma circulating levels (up to 3.0 +/- 0.2 ng.ml-1). By contrast, no sub-cutaneous LPS dose used induced early increases in ACTH and CORT levels, whereas time-course of the hormonal response was evocative of the sustained phase of the corticotropic response to i. a. LPS, with both peaks occurring 120 min post-LPS. Increasing the s. c. LPS bolus 50-fold vs the i. a. dose did not affect the maximal amplitude of the ACTH response, whereas the amplitude of the CORT response, instead, appeared dependent on the LPS dose. On the other hand, even for the largest LPS doses, plasma IL-1 beta levels remained undetectable. Sub-cutaneous injection of LPS therefore appears as a new model for the study of the mechanisms of corticotropic responses to endotoxin without a direct involvement of bloodborne IL-1 beta.

Effects of pharmacological lesion of adrenergic innervation of the dorsal vagal nucleus on pancreatic insulin secretion in normal and vagotomized rats.

Previous morphological and physiological studies have suggested that the adrenergic innervation of the dorsal motor nucleus of the vagus nerve (dmnX) is involved in direct synaptic inhibition of parasympathetic preganglionic neurones of the vagus that control secretion of pancreatic insulin. We investigated the effects of bilateral 6-hydroxydopamine (6-OHDA) lesions of adrenergic innervation of the dmnX on pancreatic insulin secretion and glycaemia in normal and vagotomized rats. After two weeks the 6-OHDA lesions produced a marked increase in circulating insulin levels, but no change in glycaemia. Hyperinsulinaemia after adrenergic denervation of the dmnX was more pronounced when a glucose bolus was injected intraarterially. Bilateral subdiaphragmatic vagotomy reversed the observed hyperinsulinaemia. This targeted pharmacological lesion of the adrenergic innervation of dmnX thus causes hypersecretion by pancreatic B cells, an effect which requires an intact vagus nerve.

Deletion of the ventral noradrenergic bundle obliterates the early ACTH response after systemic LPS, independently from the plasma IL-1ß surge.

We have recently shown that total lesion of the ventral noradrenergic bundle (VNAB-X), enhanced the short-lived (<120 min) triggering effect of intra-arterially (i.a.) given IL-1ß on plasma ACTH levels. In the present study we used the same VNAB-X paradigm to explore the mechanisms of the long-lived (480 min) LPS stimulatory effect on plasma ACTH, corticosterone (CORT) and IL-1ß levels. In control rats, 25 µg kg(-1) LPS induced a 20-fold increase in ACTH and a 7-fold increase in CORT concentrations at 30 min, which continued to rise until 60 min, before receding to baseline at 480 min. In contrast, the plasma IL-1ß concentration started to increase above undetectable levels only at 120 min. In VNAB-X animals, the early (30 min) ACTH/CORT response to LPS was completely blunted, and the ACTH surge was reduced by 75% at 60 min. However, the sustained hormonal response (120 to 480 min) was unaltered. Both the temporal pattern and the amplitude of the plasma IL-1ß response were normal. We conclude that (1) the VNAB is involved in the early (first 60 min) ACTH/CORT response to systemic LPS, (2) plasma IL-1ß does not appear to be associated with this early corticotropic activation and (3) the later stages of the ACTH/CORT response to LPS (60 to 480 min) appear to be independent of the VNAB control and may therefore involve different control mechanisms, in which the IL-1ß, by this stage massively released in the blood, may play a major role.

Short-term but not long-term adrenalectomy modulates amplitude and frequency of the CRH41 episodic release in push-pull cannulated median eminence of free-moving rats.

CRH 41 release in push-pull cannulated median eminence (ME) was measured in unanesthetized male rats, 3 and 7 days after adrenalectomy (ADX) and in sham-lesioned controls. Perfusion started at 13.30 h and perfusate samples were collected at 5 min intervals for 3 h to estimate the mean release rate of CRH41. The major parameters of the neurohormone's episodic release pattern were analyzed using the Ultra algorithm. In a parallel study, 3 groups of similarly treated rats were used to measure plasma ACTH and hypothalamic CRH41. Three days after ADX, the plasma ACTH titers had risen 14-fold, the hypothalamic CRH41 content had decreased by 40%, while the CRH41 release in the ME had doubled as a result of a significant increase in most variables of the pulsatile release pattern: pulse frequency (+34%; P < 0.01), mean amplitude (+36%; P < 0.05), mean peak levels (+67%; P < 0.01) and mean pulse nadirs (x2.5; P < 0.01). Seven days after ADX, even though plasma ACTH had further increased to 30-times control levels, hypothalamic CRH41 content and CRH41 release in the ME had returned to almost control levels. The possible mechanisms of the discrepancy between the CRH and ACTH response time-courses following ADX are discussed.

Chronic restraint enhances interleukin-1-beta release in the basal state and after an endotoxin challenge, independently of adrenocorticotropin and corticosterone release.

To explore the interactions between the hypothalamic-pituitary-adrenocortical axis and the immune system under stress conditions, we used an experimental rat model for chronic tail-restraint devised earlier for ground studies in space physiology. The system was used in two positions: (1) the orthostatic restraint position (OR) and (2) the antiorthostatic position (AOR) after the rat hind limbs had been raised by a head-down tilt. After 7 days of either restraint, sequential blood samples were taken via an indwelling aortic cannula, before and at various time intervals between 15 and 300 min after an intravascular infusion of 25 micrograms/kg lipopolysaccharide (LPS). The plasma titers of adrenocorticotropin (ACTH), corticosterone (CORT) and interleukin-1 beta (IL-1 beta) were assayed. Under basal conditions, both OR and AOR restraints induced a 5-fold increase in IL-1 beta with no significant changes in ACTH and CORT levels. A robust increase in all three variables was observed after LPS injection. However, the IL-1 beta response to LPS was significantly higher in both restrained groups than in controls. Both the amplitude and the percentage of individually restrained rats displaying elevated IL-1 beta levels were increased up to 5 h. In contrast, the ACTH and CORT post-LPS responses were normal in the OR group. They were unusually dissociated in the AOR rats, which displayed depressed ACTH levels associated with slightly increased CORT levels. Our results suggest that immune-neuroendocrine responses to chronic restraint stress may differ from those generally observed in acute stress.

Superior cervical ganglionectomy suppresses circadian corticotropic rhythms in male rats in the short term (5 days) and long term (10 days).

Superior cervical ganglionectomy (SCGx) has drastic effects on numerous hormonal circadian rhythms and particularly on pineal melatonin secretion. We investigated the hormonal consequences of ablation of the superior cervical ganglion on the corticotropic circadian rhythms in the male rat. Plasma were obtained by sampling blood every 4 h, using a chronic carotid cannula. Adreno-corticotropin hormone (ACTH) was assayed by radioimmunoassay (RIA) and corticosterone (B) by radiocompetition. Urinary 6-sulphatoxymelatonin (aMT6s), considered as an index of the pineal gland activity, was assayed by specific RIA: a decrease in the aMT6s concentration after ganglionectomy was taken as proof of adequate surgical operation. Control animals showed classical circadian rhythms for ACTH and B with basal values during the light phase and circadian peaks around the light/dark interface. Five and ten days after ganglionectomy, the circadian rhythms of ACTH and B were suppressed. In addition, the mean ACTH concentrations increased significantly 10 days after ganglionectomy compared to those in sham-operated rats and 5 days post-operation group. The mean plasma corticosterone levels were similar in those three groups of animals. This is the first study demonstrating the suppressive effect of superior cervical ganglionectomy on the circadian corticotropic hormonal cycle.

Temporal cascade of plasma level surges in ACTH, corticosterone, and cytokines in endotoxin-challenged rats.

The present study was designed to investigate the coupling mechanisms linking the immune and the neuroendocrine corticotropic systems in an integrated defense response triggered by an infectious aggression. The experimental paradigm used consisted of the exploration in individual conscious rats of the temporal pattern of increased plasma concentrations of the two stress hormones, adrenocorticotropic hormone (ACTH) and corticosterone (Cort), and of three cytokines known as ACTH stimulators, tumor necrosis factor-alpha (TNF-alpha), interleukin (IL)-1 beta, and IL-6, after intra-arterial infusions of lipopolysaccharide (LPS) given at three doses, 5 micrograms/kg (LPS-5), 25 micrograms/kg (LPS-25), and 1 mg/kg (LPS-1,000). Blood samples were taken 30 min and immediately before LPS injection (t0) and at 15, 30, 60, 120, 300, and 480 min post-LPS. The three doses of LPS induced ACTH and Cort surges, starting after 30 min for LPS-5 and LPS-25 or 15 min for LPS-1,000 and peaking with a similar amplitude at 60 min before receding slowly to baseline at 480 min for the two lower LPS doses. On the other hand, whatever the LPS dose, none of the three cytokines rose above undetectable basal levels before 60 min. They increased thereafter to culminate 10- to 30-fold above baseline at 60 min (TNF-alpha) or 120 min (IL-1 beta and IL-6) after LPS and declined back to basal levels at 300 min (TNF-alpha, all doses, and IL-6 for LPS-5 and LPS-25). After LPS-25, only IL-1 beta had not regressed to baseline levels at 480 min.(ABSTRACT TRUNCATED AT 400 WORDS)

A subpopulation of corticotropin-releasing hormone neurosecretory cells in the paraventricular nucleus of the hypothalamus also contain NADPH-diaphorase.

The coexistence of ND with CRH 41 was explored in the parvicellular neurons of the PVN, using dual histochemical and radioimmunocytochemical labelling with the light microscope, in rats treated with colchicine. Even though the ND staining was scarce, a clear colocalization was evidenced in the parvicellular part of the PVN. Under these conditions, the ratio of neurons expressing both markers, ND and CRH, amounted about 15% of the CRH-containing neuron population. This result provides a useful tool to study morphological plastic changes in the PVN in response to environmental variations.

Bursine diluee: validation des hautes dilutions / Diluted bursin: validation of the high dilutions

L'article est une etape important vers la reconnaissance et la generalisation du concept d'immunomodulation a tres faibles doses developpe par le professeur M. Bastide il y a maintenant plus de 15 ans. La thymuline... (AU)