Sub-chronic exposure to toluene at 40 ppm alters the monoamine biosynthesis rate in discrete brain areas

Effects of long-term exposure to a sub-toxic concentration of toluene (40 ppm, 104 h per week, 16 weeks) have been studied on monoamine biosypthesis rate in rat. The activities of the rate limiting enzymes in catecholamine and 5-hydroxytryptamine biosynthesis tyrosine and tryptophan hydroxylase, respectively, were estimated in vivo by measuring the accumulation of L-dihyqroxypheliylalanine and 5-hydroxytryptophan after pharmacological blockade Of L-aromatic acid decarboxylases by NSD-1015 (100mg kg(-1) ip). The sub-chronic exposure to toluene led to a significant and gender dependent alteration in both catecholamine band 5 hydroxytryptamine biosynthesis rate in brainstem catecholaminergic cell, groups and hypothalamus. In females exposed to toluene, changes in tryptophan hydroxylation were found in rostral subset of A2C2 (+41%) and in A I C 1 (+41%) while a decrease in A5 (-44%) and an increase in A2C2(+28%) were found in tyrosine hydroxylation. In males, an increase in tryptophane hydroxylation was observed in rostral subset of A2C2 (+35%) while a decrease was observed in ventro-median hypothalamus (-17%). These results suggest that toluene exposure to a dose generally recognized as sub-toxic (40 ppm, no observed adverse effect level) leads to adverse effects' on monoaminergic systems. Therefore, the neurotoxicity of toluene should be carefully re-evaluated taking into account not only the exposure level but also the duration

Behavioral and neurochemical effects induced by subchronic combined exposure to toluene at 40 ppm and noise at 80 dB-A in rats

We investigated whether exposure to noise, in addition to its well-known potentiating effect on toluene-induced ototoxicity, may also exacerbate behavioral disturbances and brain neurochemical alterations produced by subchronic exposure to low toluene concentration. To test this hypothesis, we evaluated whether subchronic combined exposure (16 weeks, 104 h per week) to noise at 80 dB-A and toluene at 40 ppm potentiates the recently reported neurotoxic effects of subchronic exposure to 40 ppm toluene. Locomotor and rearing activities, sensitization to narcosis induced by acute toluene at high concentration, and tyrosine and tryptophan hydroxylase activities in the caudate–putamen and hippocampus were investigated in both male and female rats. Our results confirm that subchronic exposure to 40 ppm toluene significantly decreases rearing activity and leads to a sensitization to toluene-induced narcosis, as evaluated by loss of righting reflex, but fails to demonstrate any adverse effect of noise, alone or in combination with toluene. Given that toluene has addictive properties, the lack of potentiating behavioral and neurochemical effect of noise is discussed with regards to a recent study that has shown that methamphetamine neurotoxicity is potentiated by exposure to loud nois

Age-related sensitivity to lung oxidative stress during ozone exposure

As immature and aged rats could be more sensitive to ozone (O3)-linked lung oxidative stress we have attempted to shed more light on age-related susceptibility to O3 with focusing our interest on lung mitochondrial respiration, reactive oxygen species (ROS) production and lung pro/antioxidant status. For this purpose, we exposed to fresh air or O3 (500 ppb 12 h per day, for 7 days) 3 week- (immature), 6 month- (adult) and 20 month-old rats (aged). We determined, in lung, H2O2 release by mitochondria, activities of major antioxidant enzymes [superoxide dismutase (SOD), glutathione peroxidase (GPx) and catalase (CAT)], heat shock protein (HSP72) content and 8-oxodG and dG-HNE nDNA contents, as DNA oxidative damage markers. In adult rats we did not observe alteration of pro/antioxidant status. In contrast to adults, immature rats exposed to O3 higher nDNA 8-oxodG content and HSP72 and without antioxidant enzymes modification. Aged rats displayed mild uncoupled lung mitochondria, increased SOD and GPx activities, and higher 8-oxodG content after O3 exposure. Thus, in contrast to adults, immature and aged rats displayed lung oxidative stress after O3 exposure. Higher sensitivity of immature to O3 was partly related to ventilatory parameters and to the absence of antioxidant enzyme response. In aged rats, the increase in cytosolic SOD and GPx activities during O3 exposure was not sufficient to prevent the impairment in mitochondrial function and accumulation in lung 8- oxodG. Finally, we showed that mitochondria seem not to be a major source of ROS under O3 exposur

Delayed maturation of catecholamine phenotype in nucleus tractus solitarius of rats with glial angiotensinogen depletion

Cerebral catecholamines and angiotensins are both involved in the regulation of cardiovascular function. Recent in vitro studies have suggested that angiotensin II modulates noradrenergic neurotransmission by controlling both the expression and neuritic trafficking of tyrosine hydroxylase (TH), the rate-limiting enzyme in catecholamine biosynthesis. To assess the potential existence of such mechanisms in vivo, we compared TH phenotype ontogeny in the nucleus tractus solitarius (NTS), which is the first central relay of the baroreflex, between control Sprague-Dawley rats and TGR(ASrAOGEN) rats (TG) with glial specific angiotensinogen (AOGEN) depletion. TG displayed a delayed increase in both TH-mRNA and TH protein levels, which sharply rises in the NTS of control rats within the fourth week. The delayed maturation of TH phenotype also affected the presence of TH protein in the neuropil, not only within the NTS region but also within the ventrolateral medulla. This was evidenced by a large decrease in the density of TH-containing neuronal processes in TG at 4 weeks only, without noticeable modification of the labeling of the neuritic marker MAP2, suggesting that neuritic trafficking of TH protein was transiently altered. These results indicate that glial AOGEN is crucial to coordinate within the fourth week the mechanisms driving the maturation of NTS catecholaminergic neurons and suggest that impairment of the central angiotensinergic system early in development can lead to cardiovascular dysfunction related to altered maturation of catecholaminergic neurons located in both the dorsal and the ventrolateral medulla