Neuroscience
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This study examined the projections from the rat insular cortex (Ins) to lower brainstem areas which are possibly involved in orofacial pain processing. We first examined distributions of Ins neurons projecting directly to the trigeminal caudal subnucleus (Vc, medullary dorsal horn) and oral subnucleus (Vo) which are known to receive orofacial nociceptive inputs. After injections of a retrograde tracer, Fluorogold (FG), into the medial part and lateral part of laminae I/II of Vc, many neurons were labeled bilaterally with a contralateral predominance in the rostral level of granular Ins (GI) and dysgranular Ins (DI) and the caudal level of GI/DI, respectively, but none in the agranular Ins (AI). ⋯ After injections of an anterograde tracer, biotinylated dextranamine (BDA), into the rostral GI/DI, many BDA-labeled axons and terminals were seen bilaterally with a contralateral predominance in the medial part of laminae I/II of Vc, dorsomedial Vo, juxtatrigeminal region, rostral ventromedial medulla (RVM), and nucleus of the solitary tract, and with an ipsilateral predominance in the parabrachial nucleus (Pb), Kölliker-Fuse nucleus (KF) and trigeminal mesencephalic nucleus. After BDA injections into the caudal GI/DI, they were seen bilaterally with a contralateral predominance in the lateral part of laminae I/II of Vc, ventrolateral Vo, juxtatrigeminal region and RVM, and with an ipsilateral dominance in the lateral zone (PAGl) of periaqueductal gray, Pb and KF. These results suggest that orofacial nociceptive processing of Vc and Vo neurons may be regulated by GI/DI directly or indirectly through brainstem nuclei such as PAGl, Pb, KF and RVM.
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Recently, we hypothesized that supraspinal structures may have important functions in discriminating between noxious mechanically and heat mediated nociception through distinct functions: facilitation and inhibition. In this study, conducted in conscious rats, we explored the role of different thalamic nuclei: the mediodorsal (MD) nucleus, the central medial (CM) nucleus, the submedius (SM) nucleus, the ventralmedial (VM) nucleus and the ventral posterolateral (VPL) nucleus, in the descending control of secondary and contralateral mechanical hyperalgesia and heat hypoalgesia occurring in intramuscularly hypertonic (HT, 5.8%) saline-induced muscle nociception. ⋯ This descending facilitatory and inhibitory modulation of nociception was strengthened by glutamate, and weakened by GABA, microinjected into the thalamic MD and VM nuclei. It is suggested that (1) thalamic MD nucleus and VM nucleus form two distinct endogenous systems in the control of noxious mechanically and heat evoked responses, and (2) the strengthening of descending inhibition and the weakening of descending facilitation by means of up regulation and down regulation of appropriate receptor expression in the VM and MD nuclei may provide a new strategic policy in treating pathological pain.
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The onset of action of antidepressants (ADs) usually takes several weeks, but first molecular responses to these drugs may appear already after acute administration. The Extracellular Signal-regulated Kinase/Mitogen-Activated Protein Kinase (ERK/MAPK) signaling pathway is a target of ADs and an important pathway involved in cellular plasticity. In major depressive disorder (MDD), especially the prefrontal cortex (PFC) and hippocampus (Hip) are most likely affected in depressive patients and recent work revealed a hyperactivated ERK signaling in the rat PFC after chronic stress, a precipitating factor for MDD. ⋯ Contrarily, at this time point none of the two ADs shows a clear modulation of astrocytic pERK. We propose that this mechanism of action of ADs may be protective against an exacerbated cortical ERK activity that may exert detrimental effects on susceptible neuronal populations. Our findings on acute effects of AD treatment in the adult mouse PFC encourage to examine further how this treatment might influence pERK in animal models of depression to identify early targets of AD action.
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Glomus cells in the carotid body are responsible for detecting changes in the partial pressure of blood oxygen (PO₂). These glomus cells have recently been found to express leptin receptors and are activated by intermittent hypoxia (IH) and systemic leptin injections, although the function of leptin within the carotid body remains unknown. The present study was done to investigate whether IH activates leptin signalling pathways within leptin-expressing carotid body glomus cells. ⋯ Furthermore, using Western blot analysis, IH was found to increase protein expression of leptin, the short form of the leptin receptor (Ob-R₁₀₀ kDa) and suppressor of cytokine signalling 3. On the other hand, IH induced a decrease in long form of leptin receptors (Ob-Rb) protein expression. Taken together, these data suggest that the increased levels of leptin within the circulation and those within the glomus cells induced by IH may alter carotid bodies chemosensitivity to hypoxic stimuli.
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Epigenetic mechanisms play an important role in memory formation and synaptic plasticity. Specifically, histone-associated heterochromatin undergoes changes in structure during the early stages of long-term memory formation. In keeping with the classical conditioning paradigm, young rats have been shown to exhibit aversion to an odor stimulus initially presented during foot shock. ⋯ We also obtained evidence that TSA infusion elevated acetylation of histone H4 or H3. Furthermore, in vitro electrophysiological analysis using slices of the OB revealed that application of TSA significantly enhanced the long-term potentiation induced in synaptic transmission from mitral to granule cells at dendrodendritic synapses. Taken together, these results provide evidence that histone H4 and H3 acetylation in the OB is an epigenetic mechanism associated with aversive olfactory learning in young rats.