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Biomedical subjects

J M Cottet-Emard

Publications and source records attributed to J M Cottet-Emard.

At least 37 records · Page 2Linked to original sources

Dexamethasone's influence on tyrosine hydroxylase activity in the chemoreflex pathway and on the hypoxic ventilatory response.

Catecholamines have been implicated in neuromodulation of peripheral chemosensitivity and central respiratory mechanisms. Because glucocorticoids can affect catecholamine metabolism in the carotid body and brainstem, this study explored the possibility that, in rats, dexamethasone or adrenalectomy affects catecholamine biosynthesis in carotid body chemoreceptors and the medullary areas (A2C2, A5, A6, A7) involved in the chemoreflex pathway and the hypoxic ventilatory response (HVR). One dexamethasone injection (1 mg/kg body wt.) stimulated tyrosine hydroxylase activity in the carotid body and had no effect in brainstem catecholamine areas, while HVR was reduced. Chronic dexamethasone (1 mg/kg body wt. daily for 10 days) had a stimulatory influence on tyrosine hydroxylase activity in the carotid body and an inhibitory effect on A2C2, A5 and A7 cell groups. Breathing pattern, but not HVR, was altered. Adrenalectomy elicited an increase in tyrosine hydroxylase activity in A2C2, which was accompanied by a decreased respiratory frequency in hypoxia. The data show that glucocorticoids have differential effects on catecholamine biosynthesis in peripheral and central structures involved in the chemoreflex pathway. Depending on the treatment, the neurochemical changes were accompanied by alterations of HVR or the breathing pattern, which are consistent with a neuromodulating influence of catecholamines on peripheral chemosensory inputs or the central respiratory network.

Adrenalectomy↗

Specific sound-induced noradrenergic and serotonergic activation in central auditory structures.

We have studied the noradrenergic and serotonergic changes induced by white noise stimulation at 70, 90 or 110 dB SPL for 45 min, in cochlear nuclei, inferior colliculus (IC), primary auditory cortex (PAC) and as a comparison in locus coeruleus (LC) and raphe dorsalis using HPLC. Both noradrenergic and serotonergic pathways were activated in the dorsal+posteroventral cochlear nuclei (DCN+PVCN) without changes in the anteroventral cochlear nucleus (AVCN) and IC. In the DCN+PVCN the noradrenergic activation was restricted to animals exposed to 70 dB SPL whereas the increase of serotonin content was intensity-dependent. In PAC serotonergic activation was observed only after 70 dB SPL exposure. These data suggest that in physiological conditions (70 dB SPL) noradrenergic and serotonergic regulation of the processing of auditory information occurs specifically in the dorsal cochlear nucleus where the control of incoming information to higher auditory structures takes place (i.e. IC and PAC). We suggest that the serotonergic activation in the primary auditory cortex for 70 dB SPL sound stimulation could be related to the fact that low-intensity white noise stimulation could be the most plastic-demanding processing in the auditory cortex.

Acoustic Stimulation↗

Changes in the sympathetic nervous system induced by 42 days of head-down bed rest.

Changes in autonomic nervous system activity could be linked to the orthostatic intolerance (OI) that individuals suffer after a spaceflight or head-down bed rest (HDBR). We examined this possibility by assessing the sympathetic nervous system activity during 42 days of HDBR in seven healthy men. Heart rate variability was studied with the use of power spectral analysis, which provided indicators of the sympathetic (SNSi) and parasympathetic (PNSi) nervous system influences on the heart. Urinary catecholamines and the spontaneous baroreflex sensitivity were measured. Urinary catecholamines decreased by 21.3%, showing a decrease in SNSi. Heart rate variability was greatly reduced during 42 days of HDBR with a drop in PNSi but with no significant changes in SNSi. The baroreflex sensitivity was greatly reduced (30.7%) on day 42 of HDBR. These results suggest a dissociation between the catecholamine response and the SNSi of the heart rate. This dissociation could be the consequence of an increase in beta-adrenergic receptor density and/or activity induced by a decrease in catecholamines during HDBR. The subjects who suffered from OI also had a greater sympathetic response and much lower baroreflex sensitivity when supine than those who finished the stand test. However, the mean response of all subjects indicated that the sympathetic activity (catecholamine excretion) was probably slightly inhibited during HDBR and could contribute to OI.

Adult↗

Effect of carbohydrate ingestion on adipose tissue lipolysis during long-lasting exercise in trained men.

To study whether sucrose administration acts on lipid mobilization during prolonged exercise, we used subcutaneous abdominal adipose tissue microdialysis in eight well-trained subjects submitted at random to two 100-min exercises (50% maximal aerobic power) on separate days. After 50 min of exercise, the subjects ingested either a sucrose solution (0.75 g/kg body wt) or water. By using a microdialysis probe, dialysate was obtained every 10 min from the subjects at rest, during exercise, and during a 30-min recovery period. During exercise without sucrose, plasma and dialysate glycerol increased significantly. With sucrose, the response was significantly lower for dialysate glycerol (P < 0.05). Plasma free fatty acid level was lower after sucrose than after water ingestion (P < 0.05). With water ingestion, plasma catecholamines increased significantly, whereas insulin fell (P < 0.05). With sucrose ingestion, the epinephrine response was blunted, whereas the insulin level was significantly increased. In conclusion, the use of adipose tissue microdialysis directly supports a lower lipid mobilization during exercise when sucrose is supplied, which confirms that the availability of carbohydrate influences lipid mobilization.

Adipose Tissue↗

Effects of a 60-day confinement on the blood pressure, hormonal responses and body fluids of a mixed crew.

During the EXEMSI experiment, an international crew of 4 subjects (1 woman and 3 men) was confined for 60 days in a normobaric diving chamber (with 1060 mbar atmospheric pressure) to simulate life in a space station and to assess the effects of confinement on psychological and physiological factors. Blood pressure and blood volume regulating hormones (atrial natriuretic peptide, renin, aldosterone) and urine data (24-h urine outputs, ionogram) were measured before (BDC: baseline data collection), during (D: day) and after (R: recovery) confinement. We also measured energy expenditure and total body water, 14 days before, and after 27 days of confinement, by the double-labeled water method. We found a marked increase in 24-h urine output during most of the confinement in the men and the woman. Body weight (-1.8 +/- 0.9 kg) and energy expenditure (-1064 +/- 143 kcal/d, p<0.01) decreased in the 3 men. The total body water (TBW) decreased by 1.5 +/- 1.2 l in the men. Stress was not indicated by plasma and urine catecholamines but plasma growth hormone was elevated on D2 (p<0.01 vs. BDC) in the men. This study shows that confinement conditions can modify body fluid (increases in 24-h urine outputs and TBW changes) and energetic metabolisms.

Adaptation, Physiological↗

Long-term influence of neonatal hypoxia on catecholamine activity in carotid bodies and brainstem cell groups of the rat.

1. In order to determine the long-term influence of neonatal hypoxia on catecholaminergic activity in peripheral arterial chemoreceptors and brainstem noradrenergic cell groups (A1, A2, A5 and A6), 1-day-old male rat pups were subjected to hypoxia (10% oxygen) for 6 days and then supplied with normal air. Control animals were kept at normoxia from birth. Rats were killed at either 3 or 8 weeks of age. 2. The content of dopamine and noradrenaline in carotid bodies of neonatally hypoxic rats was increased at both 3 and 8 weeks of age. 3. Noradrenaline turnover was selectively decreased in the caudal portion of A2 (located in the area of chemosensory afferent projection) at 8 weeks of age (-76 +/- 2%), while this turnover was unaffected in rostral A2 cells. Noradrenergic activity in A1, A5 and A6 was altered by neonatal hypoxia in an age-dependent fashion. 4. The data suggest that neonatal hypoxia induces long-term changes in the basal activity of the carotid body and brainstem noradrenergic cell groups. Such changes might contribute to neuronal regulation of the delayed respiratory, arousal and neural sequelae associated with neonatal hypoxia. These changes could also be involved in the early programming of respiratory and blood pressure control.

Animals↗

Body fluid homeostasis and cardiovascular adjustments during submaximal exercise: influence of chewing coca leaves.

The present study was undertaken to determine the haematological and cardiovascular status, at rest and during prolonged (1h) submaximal exercise (approximately 70% of peak oxygen uptake) in a group (n = 12) of chronic coca users after chewing approximately 50 g of coca leaves. The results were compared to those obtained in a group (n = 12) of nonchewers. At rest, coca chewing was accompanied by a significant increase in heart rate [from 60 (SEM 4) TO 76 (SEM 3) beats.min-1], in haematocrit [from 53.2 (SEM 1.2) to 55.6 (SEM 1.1)%] in haemoglobin concentration, and plasma noradrenaline concentration [from 2.8 (SEM 0.4) to 5.0 (SEM 0.5) mumol.l-1]. It was calculated that coca chewing for 1 h resulted in a significant decrease in blood [-4.3 (SEM 2.2)%] and plasma [-8.7 (SEM 1.2)%] volume. During submaximal exercise, coca chewers displayed a significantly higher heart rate and mean arterial blood pressure. The exercise-induced haemoconcentration was blunted in coca chewers compared to nonchewers. It was concluded that the coca-induced fluid shift observed at rest in these coca chewers was not cumulative with that of exercise, and that the hypovolaemia induced by coca chewing at rest compromised circulatory adjustments during exercise.

Adolescent↗

Effects of hydration state on hormonal and renal responses during moderate exercise in the heat.

The effects of hydromineral hormones and catecholamines on renal concentrating ability at different hydration states were examined in five male volunteers while they performed three trials. Each of these trials comprised a 60-min exercise bout on a treadmill (at 50% of maximal oxygen uptake) in a warm environment (dry bulb temperature, 35 degrees C; relative humidity, 20-30%). In one session, subjects were euhydrated before exercise (C). In the two other sessions, after thermal dehydration (loss of 3% body mass) which markedly reduced plasma volume (PV) and increased plasma osmolality (osm[pl]), the subjects exercised either not rehydrated (Dh) or rehydrated (Rh) by drinking 600 ml of mineral water before and 40 min after the onset of exercise. During exercise in the Dh compared to C state, plasma renin, aldosterone, arginine vasopressin (AVP), noradrenaline and adrenaline concentrations were increased (P < 0.05). A reduction in creatinine clearance and urine flow was also observed (P < 0.05) together with a decrease in urine osmolality, osmolar clearance and sodium excretion, while free water clearance increased (P < 0.05). However, compared to Dh, Rh partially restored PV and osm(pl) and induced a marked reduction in the time courses of both the plasma AVP and catecholamine responses (P < 0.05). Values for renal water and electrolyte excretion were intermediate between those of Dh and C. Plasma atrial natriuretic peptide presented similar changes whatever the hydration state. These results demonstrate that during moderate exercise in the heat, renal concentrating ability is paradoxically reduced by prior dehydration in spite of high plasma AVP levels, and might be the result of marked activation of the sympatho-adrenal system. Rehydration, by reducing this activation, could partially restore the renal concentrating ability despite the lowered plasma AVP.

Adrenal Glands↗

Effects of various beverages on the hormones involved in energy metabolism during exercise in the heat in previously dehydrated subjects.

The objective of our study was to examine the effects of beverage content on hormone responses involved in fuel substrate metabolism (catecholamines, insulin and glucagon) in previously dehydrated subjects exercising at a moderate intensity in the heat. Six healthy men walked for 60-min on five occasions at 50% maximal oxygen uptake in a warm environment (dry bulb temperature 35 +/- 0.2 degrees C, relative humidity 20%). On each occasion, the subjects were dehydrated before exercise (loss of 2% body mass) by passive controlled hyperthermia, which led to a reduction in plasma volume (PV) of about -5% to -9%. In one session, the subjects exercised without rehydration (Dh). In the other sessions, four beverages (650 ml) were given just before the exercise: mineral water (W), a 60 g x l(-1) glucose and 1.2 g x l(-1) NaCl solution (GS), a 60 g x l(-1) maltodextrin solution, and a 60 g x l(-1) maltodextrin and 1.2 g x l(-1) NaCl solution. Compared to Dh and W, carbohydrate supply with or without NaCl induced a higher glycaemia (P < 0.05), a reduced increase in plasma adrenaline concentration (P < 0.05) and a higher plasma insulin concentration (P < 0.05), which lowered plasma free fatty acids and glycerol concentrations (P < 0.05). The lesser increase in plasma noradrenaline concentrations observed during GS compared to Dh and W sessions can be explained by a larger correction in PV which might have induced better haemodynamic conditions. However, the increase in plasma glucagon with carbohydrate supply--compared to Dh and W (P < 0.05)--remains unexplained.

Adult↗

Long-term exposure to ozone alters peripheral and central catecholamine activity in rats.

In addition to its noxious influence on lung airways, ozone inhalation can induce extrapulmonary neural dysfunctions the mechanisms of which are poorly understood. This study was intended to characterize the effects of long-term exposure to ozone (0.5 ppm, 5 days) on catecholamine activity in rat sympathetic efferents and brain areas of prime importance to adaptation to environmental stressors. Catecholamine activity was assessed by estimating the turnover rate of catecholamines and in vivo tyrosine hydroxylase activity in peripheral and central structures, i.e., heart, lungs, superior cervical ganglia, cerebral cortex, hypothalamus and striatum, A2 cell group within the nucleus tractus solitarius (NTS), and locus ceruleus (A6). Ozone inhibited norepinephrine turnover in heart (-48% of the control level) but not in lungs. Ozone failed to modify the tyrosine hydroxylase activity in superior cervical ganglia, and the catecholamine content in the adrenal glands. In the central nervous system, ozone inhibited tyrosine hydroxylase activity in noradrenergic brainstem cell groups, including the locus ceruleus (-62%) and the caudal A2 subset (-57%). Catecholamine turnover was decreased by ozone in the cortex (-49%) and striatum (-18%) but not in the hypothalamus. The data show that ozone can produce marked neural disturbances in structures involved in the integration of chemosensory inputs, arousal, and motor control.

Adrenal Glands↗

Brain monoamines and optokinetic performances in pigmented and albino rats.

The aim of this study was two-fold: 1) To provide in DA-HAN rats the basic brain monoamine data useful for later investigations of the neurochemical effects of sensory alterations and 2) to assess whether there is a relationship between the monoaminergic pattern in medial vestibular nuclei and optokinetic performances. We comparatively studied the regional brain monoamine distribution and the optokinetic performances in pigmented DA-HAN and albino Sprague-Dawley rats. As expected, the optokinetic responses and vestibulo-ocular reflex gain were by far more efficient in DA-HAN rats. Norepinephrine (NE), dopamine (DA), serotonin (5-HT) and their metabolites were determined in retina, brainstem nuclei and dopaminergic areas. DA-HAN rats exhibited an increased noradrenergic activity in the medial vestibular nuclei, locus coeruleus and anteroventral cochlear nucleus, an extended decrease of serotonergic activity in brainstem nuclei and increased DA stores with a reduced dopaminergic activity in most dopaminergic areas. These data confirm and extend the general findings that biochemical data obtained in one strain cannot be extrapolated to another strain. The possible role of the morphological neuronal abnormalities and functional impairment induced by albinism has been discussed especially in medial vestibular nucleus, cochlear nuclei and retina. Alternatively, behavioral factors may also explain some of the observed neurochemical differences.

Albinism↗

Peripheral chemosensitivity and central integration: neuroplasticity of catecholaminergic cells under hypoxia.

The plasticity of catecholaminergic cells within the carotid body, brainstem and sympatho-adrenal system was analyzed in rats subjected to normobaric hypoxia (10% O2) lasting up to 3 weeks. Long-term hypoxia elicited structural, neurochemical and phenotypic changes in carotid body and sympathetic ganglia (SIF cells), and stimulated the norepinephrine turnover in A2 neurons located caudal to the obex, the area where the chemosensory nerve fibers end. Chemodenervation abolished central alterations. Adaptive mechanisms for increasing norepinephrine biosynthesis in hypoxia involved changes in activity of pre-existing tyrosine hydroxylase, the rate-limiting enzyme of catecholamine biosynthesis, and induction of new tyrosine hydroxylase protein. These neurochemical changes occurred after sustained hypoxia only, suggesting that noradrenergic neurons are involved in the central chemoreceptor pathway during sustained hypoxia but are not essential for regulatory responses to acute hypoxia. Acute hypoxia elicited the expression of c-Fos protein in neurons located in nucleus tractus solitarius that were not catecholaminergic. Noradrenaline released under long-term hypoxia could play a neuromodulatory role in ventilatory acclimatization. Cardiovascular responses to hypoxia are mediated by changes in sympatho-adrenal outflow, different according to the target organ. Cardiac sympathetic output and adrenal secretion were stimulated independently of carotid body chemoafferents. Early postnatal hypoxia induced long-term neurochemical changes in carotid body, brainstem and sympathetic efferents that may reveal alterations in development of neurons involved in the chemoreceptor pathway.

Adrenal Glands↗

Carotid body dopamine content and release by short-term hypoxia: effect of haloperidol and alpha methyl paratyrosine.

Dopamine (DA) is thought to modulate the transduction of the hypoxic stimulus by the glomus cell in the carotid body (CB). The hypothesis tested here is that presynaptic DA D2 receptors (D2's) located on the type 1 cell function as autoreceptors to control DA release and/or synthesis. The aim of the study was to compare the effects of blocking D2's with haloperidol and DA synthesis with alpha methyl paratyrosine (AMPT) on the in vitro carotid body DA response to hypoxia. 54 CB's sampled from adult rabbits were incubated for one hour in a surviving medium bubbled with either 100% O2 or 8% O2 Sixteen CB's served as control (100% O2: n = 8, 8% O2: n = 8), 18 (100% O2: n = 8, 8% O2: n = 10) were sampled from rabbits pretreated with AMPT and 20 (100% O2: n = 12, 8% O2: n = 8) were incubated with micromolar concentrations of haloperidol. At the end of exposure. DA contained in the carotid body (DACB) and released in the surviving medium (DAr) were measured by HPLC. In 100% O2 DACB was not different between either AMPT or haloperidol and control, but DAr was significantly higher in the haloperidol group compared with control (mean +/- SE: 26.6 +/- 7.4 versus 7.6 +/- 2.0 pmol/h, P < 0.02). In 8% O2, control DACB (576 +/- 133 pmol/CB) was significantly higher than AMPT or haloperidol (respectively 228 +/- 29.6 and 246 +/- 49.9 pmol/CB, P < 0.01) and control DAr (234 +/- 72.3 pmol/h) was also significantly higher than AMPT or haloperidol (respectively 28.8 +/- 5.2 and 40.6 +/- 11.4 pmol/h, P < 0.01). Finally, DAr was significantly larger in 8% O2 than in 100% O2 in control and AMPT groups (P < 0.01), but not in the haloperidol group. The increase in DAr by haloperidol in the resting CB is consistent with the blockade of D2's regulating DA release. The decreased DAr in 8% O2 after AMPT suggests that increased DA synthesis contributes to maintain DA secretion by the type I cell exposed to short term hypoxia. The lack of difference in DAr between 8% O2 and 100% O2 after haloperidol probably reflects non specific--i.e., D2 independent--effect of micromolar concentration of haloperidol on DA synthesis and/or sodium-calcium exchangers during hypoxia.

Analysis of Variance↗

Glucose administration before exercise modulates catecholaminergic responses in glycogen-depleted subjects.

In glycogen-depleted subjects (GD) a nonlinear increase in epinephrine (Epi) and norepinephrine (NE) parallels blood lactate (La) during graded exercise. The effect of glucose (Glc) supplementation and route of administration on these relationships was studied in 26 GD athletes who were randomly assigned to receive 1.3 g/kg Glc by slow intravenous infusion (IV; n = 9), oral administration (PO; n = 9), or artificially sweetened placebo in 1 liter of water (Asp; n = 8) in the 2 h preceding a graded maximal exercise. Performance and La were similar among the three groups in normal glycogen (NG) or GD conditions. However, slightly improved performances were observed in GD compared with NG and were associated with a shift to the right in La curves. Blood Glc concentrations were higher in IV and PO before exercise, but they rapidly decreased to lowest levels in IV, gradually decreased over time in PO, and remained stable in Asp or NG. Insulin concentrations were highest in IV and lowest in Asp and NG at onset of exercise, rapidly decreasing in IV and PO although remaining at higher levels than in Asp or NG. In contrast, higher serum levels of free fatty acids were measured during exercise in Asp with no significant differences in glucagon or glycerol among the three groups. Free and sulfated NE increases were smaller in IV than in PO and Asp on exhaustion. In contrast, free and conjugated Epi were most increased in IV, with smallest increases in Asp. Dopamine levels were most increased in IV at exhaustion. We conclude that the changes of Epi and NE concentrations, associated with the activation of glucoregulatory mechanisms, including hyperinsulinemia, display different magnitude and time courses during exercise in GD subjects who receive oral vs. intravenous load of Glc before exercise. We speculate that the magnitude of insulin surge after acutely increased Glc before exercise in GD subjects may exert dissociative effects on adrenal-dependent glycogenolysis and on sympathetic responses.

Adult↗

Fluid regulatory hormone response to exercise after coca-induced body fluid shifts.

To determine the effect of coca chewing on heart rate (HR), mean arterial blood pressure (MAP), and plasma volume and their relationship with the hormones regulating cardiovascular and body fluid homeostasis, 16 male volunteers were examined at rest and during 1 h of cycle exercise at approximately 75% of their peak oxygen uptake in two trials separated by 1 mo. One trial was performed after the subjects chewed a sugar-free chewing gum (Coca- trial), whereas the other was done after the subjects chewed 15 g of coca leaves (Coca+), with the order of the Coca- and Coca+ trials being randomized. Blood samples were taken at rest, before (R1) and after 1-h chewing (R2), and during the 5th, 15th, 30th, and 60th min of exercise. They were analyzed for hematocrit, hemoglobin concentration, red blood cell count, plasma proteins, and for the fluid regulatory hormones, including plasma catecholamines [norepinephrine (NE) and epinephrine], renin, arginine vasopressin, and the atrial natriuretic peptide (ANP). During the control trial (Coca-), from R1 to R2, there was no significant change in hematologic, hormonal, and cardiovascular status except for a small increase in plasma NE. In contrast, it can be calculated that coca chewing at rest induced a significant hemoconcentration (-3.8 +/- 1. 3% in blood and -7.0 +/- 0.7% in plasma volume), increased NE and MAP, and reduced plasma ANP. Chewing coca before exercise reduced the body fluid shifts but enhanced HR response during exercise. These effects were not accompanied by changes in NE, epinephrine, renin, and arginine vasopressin plasma levels. In contrast, plasma ANP response to exercise was lower during the Coca+ trial, suggesting that central cardiac filling was reduced by coca use. It is likely that the reduction in body fluid volumes is a major contributing factor to the higher HR at any given time of exercise after coca chewing.

Adult↗

Long-term impairment in the neurochemical activity of the sympathoadrenal system after neonatal hypoxia in the rat.

The study evaluates the long-term effect of neonatal hypoxia on the neurochemical activity of the sympathoadrenal system in the rat. One-day-old male pups were exposed to hypoxia (10% O2) for 6 d and thereafter reared under normoxia. Neonatal hypoxia reduced the body weight of 3- and 8-wk-old rats and did not change the blood pressure at 6 wk of age. In sympathetic ganglia, the content and/or turnover rates of norepinephrine were reduced in neonatal-hypoxic rats of 3 and 8 wk of age, but the content and turnover rates of dopamine were unaltered. The effect was not dependent on the type of ganglion. In the superior cervical ganglion, neonatal hypoxia had a selective effect on the type of catecholamine (dopamine versus norepinephrine), thus suggesting a selective-altered maturation of noradrenergic neurons, but presumably not of the dopaminergic small, intensely fluorescent cells. A long-term deficiency in adrenal activity was the consequence of neonatal hypoxia, as shown by the decrease in the content and turnover rate of dopamine. Neonatal hypoxia elicited a long-term decrease in the content and turnover rates of norepinephrine in heart and lungs but failed to induce a significant effect in kidneys. However, this effect was not tissue-specific. Data provide evidence that a hypoxic episode occurring during a critical period of development in the rat induces a long lasting decrease in the neurochemical activity of the sympathoadrenal system. These results are discussed in terms of their implications for human pathology.

Adrenal Glands↗

Monoamines (norepinephrine, dopamine, serotonin) in the rat medial vestibular nucleus: endogenous levels and turnover.

Monoamine (norepinephrine, dopamine, serotonin) and metabolite endogenous levels were determined in the rat medial vestibular nucleus (MVN) using HPLC with electrochemical detection. As a comparison, the locus coeruleus (LC) and dorsal raphe nucleus (RD) which contain the cell bodies of MVN noradrenergic and serotoninergic neurons respectively were also analyzed. Norepinephrine (NE) and serotonin (5-HT) basal levels of MVN were high (33.8 and 39.2pmol/mg protein respectively) but lesser than in LC or RD. Great amounts of MHPG and 5-HIAA were also present in the MVN. The turnover of NE assessed both from the ratio MHPG/NE and by the decrease in the NE content after treatment with alpha-methylparatyrosine was faster in the MVN (half-life: 1.5h) than in LC (half-life: 3.6h). On the other hand, the ratio 5-HIAA/5-HT was lower in the MVN (0.58) than in the RD (0.85) indicating a smaller 5-HT turnover in the MVN. In addition, like LC and RD, the MVN contained meaningful amounts of dopamine (DA) and DOPAC. The high ratio DA/NE (0.27) suggests the presence of non precursor specific dopaminergic pools. However, individualized dopaminergic neurons have not yet been demonstrated. The data are discussed in line with the possible neurotransmitter function of monoamines in the MVN.

3,4-Dihydroxyphenylacetic Acid↗

Aging effects on monoamines in rat medial vestibular and cochlear nuclei.

Noradrenaline (NA), dopamine (DA); serotonin (5-HT) and their metabolites-3-methoxy, 4-hydroxyphenylglycol (MHPG), 3,4-dihydroxyphenylacetic acid (DOPAC) and 5-hydroxyindoleacetic acid (5-HIAA)-were determined using HPLC in medial vestibular nucleus (MVN), anteroventral cochlear nucleus (AVCN), dorsal+posteroventral cochlear nucleus (DCN+PVCN), locus coeruleus (LC) and raphe dorsalis of Dark Agouti-Hanovre (DA-HAN) rats aged 4, 21 and 24 months. In older rats, the main noradrenergic changes were a decrease of NA content with an increase of the MHPG/NA ratio in MVN and a selective NA increase in AVCN. 5-HT and 5-HIAA levels were increased in all the brainstem nuclei except raphe dorsalis. DA and DOPAC remained unchanged. These data show that noradrenergic neurons in sensory nuclei are differently affected by aging whereas serotonergic activation occurs in most of them possibly as a compensatory response to dysfunction of sensory input and processing. The increase of NA stores in the AVCN of aged rats is in line with the elevated auditory brainstem threshold reported in old rats and could improve the signal-to-noise ratio. Noradrenergic neurons in the MVN seem to be more sensitive to age effect than cochlear nuclei; however, even if neuronal loss occurs, NA synthesis and/or metabolism increase to ensure normal or increased noradrenergic activity.

3,4-Dihydroxyphenylacetic Acid↗