Forebrain lead levels

Figure 20.6 Schematic representation of the effects of 5-HT reuptake inhibitors on serotonergic neurons, (a) 5-HT is released at the somatodendritic level and by proximal segments of serotonergic axons within the Raphe nuclei and taken up by the 5-HT transporter. In these conditions there is little tonic activation of somatodendritic 5-HTia autoreceptors. At nerve terminals 5-HTib receptors control the 5-HT synthesis and release in a local manner, (b) The blockade of the 5-HT transporter at the level of the Raphe nuclei elevates the concentration of extraneuronal 5-HT to an extent that activates somatodendritic autoreceptors (5-HTia). This leads to neuronal hyperpolarisation, reduction of the discharge rate and reduction of 5-HT release by forebrain terminals, (c) The exposure to an enhanced extracellular 5-HT concentration produced by continuous treatment with SSRIs desensitises Raphe 5-HTia autoreceptors. The reduced 5-HTia function enables serotonergic neurons to recover cell firing and terminal release. Under these conditions, the SSRI-induced blockade of the 5-HT transporter in forebrain nerve terminals results in extracellular 5-HT increases larger than those observed after a single treatment with SSRIs. (Figure and legend taken from Hervas et al. 1999 with permission)...

Central/Tertiary structures The fish olfactory bulb is a fourlayered structure much as in higher vertebrates. Within the 2nd layer, the first synapse for olfactory input is on the dendrites of the mitral cells (MC). About 1000 ORN axons converge on one MC, a ratio similar to mammals. The MC output, from cells at various levels, leads into several glomeruli and receives (inhibitory) input from granule cells. The latter also innervate a distinct cell type in the MC layer of teleosts — the ruffed cells (RC), with which they have reciprocal synapses [Fig. 2.18(a)] both relay cells send ascending fibres to forebrain centres (Kosaka and Hama, 1982). The RC are unlike the MC since they are not stimulated by the ORNs directly. Their interactions (Chap. 5) may contribute to the processing of pheromonal stimuli (Zippel, 2000). The main bulbar pathways project to several nuclei in the forebrain via two ipsilateral tracts, the lateral and medial [Fig. 2.18(b)], the latter mediates sexual behaviour and the former probably other behaviours (Hara,... 

Catecholamine levels in the obese-infected mice were reduced significantly in forebrain, but not in the brain stem (Lyons et al., 1982). In substantia nigra, CDV infection downregulates tyrosine hydroxylase (TH), the rate-limiting enzyme of dopamine synthesis, which leads to motor impairment of infected animals (Bencsik et al., 1996). 

Early research concentrated on the effects of lead on endogenous levels of neurotransmitters. Some reports indicated increased noradrenaline in whole brain (Goiter and Michaelson, 1975), forebrain (Silbergeld and Goldberg, 1975), midbrain (Dubas and Hrdina, 1978) and brainstem (Jason and Kellogg, 1977) while others indicated no changes (Sauerhoff and Michaelson, 1973 Sobotka et al., 1975 Grant et al., 1976). 

In conclusion, data from low level studies, in which vascular change and undernutrition do not occur, suggest the possibility of specific lead effects on neuronal populations in the forebrain (notably the hippocampus) and cerebellum. To what extent such effects are related to the suspected human problem of subclinical lead neurotoxicity may only emerge after prolonged and intensive study. 

S-HT occurs in the central nervous system of all vertebrates and seems to be concentrated in the phylogenetically older parts of the brain connected with the autonomic nervous system and the reticular formation (Table 2). The use of histofluorescence techniques has made it possible to confirm the finding of uneven regional S-HT distribution based on chemical and biochemical assays. S-HT neurons have now been visualized (Fig. 7 and Fig. 10 in Sect B, Chap. S.2). Most S-HT neurons seem to be located in the nuclei of the raphe system and their axons travel towards several parts of the brain and the spinal cord. These axons are particularly concentrated in the medial forebrain bundle (MFB) (Fig. 7X which can be selectively destroyed, leading to a significant decrease in S-HT in some areas of the brain. Diurnal and seasonal variations in S-HT levels in several areas of the brain have been demonstrated. 

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