Neuroscience
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In nocturnal rodents, brain areas that promote wakefulness have a circadian pattern of neural activation that mirrors the sleep/wake cycle, with more neural activation during the active phase than during the rest phase. To investigate whether differences in temporal patterns of neural activity in wake-promoting regions contribute to differences in daily patterns of wakefulness between nocturnal and diurnal species, we assessed Fos expression patterns in the tuberomammillary (TMM), supramammillary (SUM), and raphe nuclei of male grass rats maintained in a 12:12 h light-dark cycle. ⋯ While CTB labeling was scarce in the TMM and other hypothalamic areas including the suprachiasmatic nucleus, which contains the main circadian pacemaker, a dense cluster of CTB-positive neurons was evident in the caudal dorsal raphe, and the majority of these neurons appeared to be serotonergic. Since these findings are in agreement with reports for nocturnal rodents, our results suggest that the evolution of diurnality did not involve a change in the overall distribution of neuronal connections between systems that support wakefulness and their target areas, but produced a complete temporal reversal in the functioning of those systems.
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The aim of this study was to test the insulin-like growth factor-I (IGF-I) as a neuroprotective agent in a rat model for ischemic stroke and to compare its neuroprotective effects in conscious normotensive and spontaneously hypertensive rats. The effects of subcutaneous IGF-I injection were investigated in both rat strains using the endothelin-1 rat model for ischemic stroke. Motor-sensory functions were measured using the Neurological Deficit Score. ⋯ Furthermore, IGF-I significantly reduced microglial activation in the cortex of hypertensive rats, but not in normotensive rats. More detailed studies are required to find out whether the reduction by IGF-I of microglial activation contributes to an impairment IGF-I treatment efficacy. Indeed, we have shown before that microglia in hypertensive rats have different properties compared to those in control rats, as they exhibit a reduced responsiveness to ischemic stroke and lipopolysaccharide.
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Previous behavioral studies have revealed that CaV3.2 T-type calcium channels support peripheral nociceptive transmission and electrophysiological studies have established the presence of T-currents in putative nociceptive sensory neurons of dorsal root ganglion (DRG). To date, however, the localization pattern of this key nociceptive channel in the soma and peripheral axons of these cells has not been demonstrated due to lack of isoform-selective anti-CaV3.2 antibodies. In the present study a new polyclonal CaV3.2 antibody is used to localize CaV3.2 expression in rodent DRG neurons using different staining techniques including confocal and electron microscopy (EM). ⋯ Further, EM revealed immuno-gold labeling of CaV3.2 preferentially in association with unmyelinated sensory fibers from mouse sciatic nerve. Finally, we demonstrated the expression of CaV3.2 channels in peripheral nerve endings of mouse hindpaw skin as shown by co-localization with Mrgpd-GFP-positive fibers. The CaV3.2 expression within the soma and peripheral axons of nociceptive sensory neurons further demonstrates the importance of this channel in peripheral pain transmission.
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17α-Ethynyl-estradiol (EE2, a synthetic steroidal estrogen) induces antidepressant-like effects in the forced swimming test (FST) similar to those induced by 5-HT and noradrenaline reuptake inhibitors (dual antidepressants). However, the precise mechanism of action of EE2 has not been studied. In the present study, the participation of estrogen receptors (ERs) and the serotonergic and the noradrenergic presynaptic sites in the antidepressant-like action of EE2 was evaluated in the FST. ⋯ The ER antagonist, 5,7-DHT, DSP4, and idazoxan blocked the effects of EE2 on the immobility behavior, whereas ICI 182,780 and 5,7-DHT affected swimming behavior. The noradrenergic compound DSP4 altered climbing behavior, while Idazoxan inhibited the increase of swimming and climbing behaviors induced by EE2. Our results suggest that the antidepressant-like action of EE2 implies a complex mechanism of action on monoaminergic systems and estrogen receptors.
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Proinflammatory cytokines such as tumor necrosis factor-α and interleukin-1β (IL1β) regulate both excitatory and inhibitory synaptic transmission in the central nervous system. The interaction between IL1β and endocannabinoid system (ECS) is also emerging, based on the evidence that IL1β effects on striatal spontaneous excitatory and inhibitory postsynaptic currents are regulated by transient receptor potential vanilloid 1 (TRPV1) channels, members of the ECS. Furthermore, IL1β has also been shown to control the sensitivity of cannabinoid CB1 receptors controlling GABA transmission (CB1Rs(GABA)) in the striatum. ⋯ IL1β failed to modulate the sensitivity of glutamate synapses to the stimulation of GABAB receptors. We also provided evidence that IL1β-CB1Rs(GABA) but not IL1β-CB1Rs(glu) interaction is under the control of the brain-derived neurotrophic factor (BDNF)/trkB signaling and of lipid raft composition, because BDNF gene partial deletion, pharmacological blockade of trkB and membrane cholesterol removal with methyl-β-cyclodextrin all blocked IL1β-mediated inhibition of CB1Rs(GABA) but left unaltered the sensitivity of CB1Rs(glu) to this cytokine. Our results provide further evidence that synaptic transmission and the ECS are regulated by IL1β in the striatum.