Abstract
The expression of c-Fos defines brain regions activated by the stressors hypotension and glucoprivation however, whether this identifies all brain sites involved is unknown. Furthermore, the neurochemicals that delineate these regions, or are utilized in them when responding to these stressors remain undefined. Conscious rats were subjected to hypotension, glucoprivation or vehicle for 30, 60 or 120 min and changes in the phosphorylation of serine residues 19, 31 and 40 in the biosynthetic enzyme, tyrosine hydroxylase (TH), the activity of TH and/or, the expression of c-Fos were determined, in up to ten brain regions simultaneously that contain catecholaminergic cell bodies and/or terminals: A1, A2, caudal C1, rostral C1, A6, A8/9, A10, nucleus accumbens, dorsal striatum and medial prefrontal cortex. Glucoprivation evoked phosphorylation changes in A1, caudal C1, rostral C1 and nucleus accumbens whereas hypotension evoked changes A1, caudal C1, rostral C1, A6, A8/9, A10 and medial prefrontal cortex 30 min post stimulus whereas few changes were evident at 60 min. Although increases in pSer19, indicative of depolarization, were seen in sites where c-Fos was evoked, phosphorylation changes were a sensitive measure of activation in A8/9 and A10 regions that did not express c-Fos and in the prefrontal cortex that contains only catecholaminergic terminals. Specific patterns of serine residue phosphorylation were detected, dependent upon the stimulus and brain region, suggesting activation of distinct signaling cascades. Hypotension evoked a reduction in phosphorylation in A1 suggestive of reduced kinase activity. TH activity was increased, indicating synthesis of TH, in regions where pSer31 alone was increased (prefrontal cortex) or in conjunction with pSer40 (caudal C1). Thus, changes in phosphorylation of serine residues in TH provide a highly sensitive measure of activity, cellular signaling and catecholamine utilization in catecholaminergic brain regions, in the short term, in response to hypotension and glucoprivation.
Highlights
Hypotension and glucoprivation are two physical stressors
With respect to hypotension limited brain sites including the nucleus of the solitary tract (NTS), ventrolateral medulla (VLM), A5 cell group, A6 cell group, periaquaductal grey (PAG), central amygdaloid nucleus (CeA), supraoptic nucleus (SON), lateral hypothalamic area (LHA), paraventricular nucleus (PVN), and bed nucleus of the stria terminalis (BNST) are activated [1,2,3], whereas with glucoprivation the NTS, VLM, A6, PAG, CeA, LHA, dorosmedial hypothalamus (DMH), PVN, ventral palladis (VP) and nucleus accumbens (NAc) are activated [4,5,6]
It is very difficult to quantify such data some evidence of increased phosphorylation evoked by hydralazine compared to saline treatment may be seen in the cC1 and A6 regions using pSer19 and pSer31 antibodies (Fig. 3).The results of western blot analysis in subsequent Figures are all expressed as Ser40 phosphorylation/total tyrosine hydroxylase (TH), Ser31 phosphorylation/total TH and Ser19 phosphorylation/total TH for each brain region
Summary
Hypotension and glucoprivation are two physical stressors. Hypotension unloads baroreceptors, which leads to the activation or inhibition of a number of brain sites in an attempt to restore arterial pressure (AP). With respect to hypotension limited brain sites including the nucleus of the solitary tract (NTS), ventrolateral medulla (VLM), A5 cell group, A6 cell group (not in rat), periaquaductal grey (PAG), central amygdaloid nucleus (CeA), supraoptic nucleus (SON), lateral hypothalamic area (LHA), paraventricular nucleus (PVN), and bed nucleus of the stria terminalis (BNST) are activated [1,2,3], whereas with glucoprivation the NTS, VLM, A6, PAG, CeA, LHA, dorosmedial hypothalamus (DMH), PVN, ventral palladis (VP) and nucleus accumbens (NAc) are activated [4,5,6] This technique has proven extremely valuable, little is known about the neurotransmitters/neurochemistry involved, the brain sites that may be inhibited, whether c-Fos is turned on in all sites that are activated or the time course of effect
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