Characterization of the neurochemical content of neuronal populations of the lamina terminalis activated by acute hydromineral challenge.

The lamina terminalis (LT) contains three main regions, namely the subfornical organ (SFO), the median preoptic nucleus (MnPO) and the vascular organ of the LT (OVLT). Although LT is recognized of paramount importance in the regulation of hydromineral homeostasis, identity of the neurocircuits interconnecting the SFO and OVLT to the MnPO is not known. Furthermore, the phenotype of neuronal populations activated during acute hydromineral challenge is not yet determined. By using the high cellular resolution of the in situ hybridization histochemistry (ISHH), we investigated whether a furosemide-induced fluid and electrolyte depletion might modify both putative GABAergic and glutamatergic systems within the LT. We show that acute furosemide treatment (4 h) significantly reduced the expression of GAD67 mRNA, the active holoenzyme predictive of GABA synthesis, within the SFO. A strong tendency toward a reduction of GAD67 signal was also observed in the OVLT and MnPO. The hydromineral challenge did not alter the expression of GAD65 and type 2 vesicular glutamate transporter (vGlut2) mRNA in all the structures of the LT. Furosemide treatment was associated with a reduction in the population of GAD67-containing neurons in the periphery of the SFO and dorsal part of the MnPO. Contrastingly, GAD65-containing cells were shown to be increased in the OVLT and no change was observed for the vGlut2-containing neurons in the whole LT. By combining ISHH with immunohistochemistry (Fos immunoreactivity), we report that furosemide-induced water and sodium depletion did essentially recruit a glutamatergic network throughout the LT, although GABAergic neurons were specifically activated in the ring of the SFO and in the OVLT. The MnPO, the region of the LT that is considered as being an integrative area for sensory inputs arising from the SFO and OVLT, showed exclusive activation of excitatory neuronal populations. Taken together these results suggest that acute water and Na(+) depletion diminish the efficacy of the GABAergic system and mainly activates excitatory neuronal pathways in the regions of the LT.

Role of endogenous opioid system in the regulation of the stress response.

Numerous studies and reviews support an important contribution of endogenous opioid peptide systems in the mediation, modulation, and regulation of stress responses including endocrine (hypothalamopituitary-adrenal, HPA axis), autonomic nervous system (ANS axis), and behavioral responses. Although several discrepancies exist, the most consistent finding among such studies using different species and stressors is that opioids not only diminish stress-induced neuroendocrine and autonomic responses, but also stimulate these effector systems in the non-stressed state. A distinctive feature of the analgesic action of opioids is the blunting of the distressing, affective component of pain without dulling the sensation itself. Therefore, opioid peptides may diminish the impact of stress by attenuating an array of physiologic responses including emotional and affective states. The widespread distribution of enkephalin (ENK) throughout the limbic system (including the extended amygdala, cingulate cortex, entorhinal cortex, septum, hippocampus, and the hypothalamus) is consistent with a direct role in the modulation the stress responses. The predictability of stressful events reduces the impact of a wide range of stressors and ENK appears to play an important role in this process. Therefore, ENK and its receptors could represent a major modulatory system in the adaptation of an organism to stress, balancing the response that the stressor places on the central stress system with the potentially detrimental effects that a sustained stress may produce. Chronic neurogenic stressors will induce changes in specific components of the stress-induced ENKergic system, including ENK, delta- and mu-opioid receptors. This review presents evidences for adaptive cellular mechanisms underlying the response of the central stress system when assaulted by repeated psychogenic stress, and the involvement of ENK in these processes.

Effect of chronic psychogenic stress exposure on enkephalin neuronal activity and expression in the rat hypothalamic paraventricular nucleus.

This study tested the hypothesis that the activation pattern of enkephalinergic (ENKergic) neurons within the paraventricular nucleus of the hypothalamus (PVH) in response to psychogenic stress is identical whether in response to repeated exposure to the same stress (homotypic; immobilization) or to a novel stress (heterotypic; air jet puff). Rats were assigned to either acute or chronic immobilization stress paradigms (90 min/day for 1 or 10 days, respectively). The chronic group was then subjected to an additional 90-min session of either heterotypic or homotypic stress. A single 90-min stress session (immobilization or air jet) increased PVH-ENK heteronuclear (hn) RNA expression. In chronically stressed rats, exposure to an additional stress session (whether homotypic or heterotypic) continued to stimulate ENK hnRNA expression. Acute immobilization caused a marked increase in the numbers of Fos-immunoreactive and Fos-ENK double-labeled cells in the dorsal and ventral medial parvicellular, and lateral parvicellular subdivisions of the PVH. Chronic immobilization caused an attenuated Fos response ( approximately 66%) to subsequent immobilization. In contrast, chronic immobilization did not impair ENKergic neuron activation within the PVH following homotypic or heterotypic stress. These results indicate that within the PVH, chronic psychogenic stress markedly attenuates the Fos response, whereas ENKergic neurons resist habituation, principally within the ventral neuroendocrine portion of the nucleus. This suggests an increase in ENK effect during chronic stress exposure. Homotypic (immobilization) and heterotypic (air jet) psychogenic stressors produce similar responses, including Fos, ENK-Fos, and ENK hnRNA, within each subdivision of the PVH, suggesting similar processing for painless neurogenic stimuli.

Overexpression of human apolipoprotein A-II in mice induces hypertriglyceridemia due to defective very low density lipoprotein hydrolysis.

Two lines of transgenic mice, hAIItg-delta and hAIItg-lambda, expressing human apolipoprotein (apo)A-II at 2 and 4 times the normal concentration, respectively, displayed on standard chow postprandial chylomicronemia, large quantities of very low density lipoprotein (VLDL) and low density lipoprotein (LDL) but greatly reduced high density lipoprotein (HDL). Hypertriglyceridemia may result from increased VLDL production, decreased VLDL catabolism, or both. Post-Triton VLDL production was comparable in transgenic and control mice. Postheparin lipoprotein lipase (LPL) and hepatic lipase activities decreased at most by 30% in transgenic mice, whereas adipose tissue and muscle LPL activities were unaffected, indicating normal LPL synthesis. However, VLDL-triglyceride hydrolysis by exogenous LPL was considerably slower in transgenic compared with control mice, with the apparent Vmax of the reaction decreasing proportionately to human apoA-II expression. Human apoA-II was present in appreciable amounts in the VLDL of transgenic mice, which also carried apoC-II. The addition of purified apoA-II in postheparin plasma from control mice induced a dose-dependent decrease in LPL and hepatic lipase activities. In conclusion, overexpression of human apoA-II in transgenic mice induced the proatherogenic lipoprotein profile of low plasma HDL and postprandial hypertriglyceridemia because of decreased VLDL catabolism by LPL.