Neuroscience
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Disruption of bacterial colonization during the early postnatal period is increasingly being linked to adverse health outcomes. Indeed, there is a growing appreciation that the gut microbiota plays a role in neurodevelopment. However, there is a paucity of information on the consequences of early-life manipulations of the gut microbiota on behavior. ⋯ Both treatments did not alter visceral pain perception in female rats. Changes in visceral pain perception in males were paralleled by distinct decreases in the transient receptor potential cation channel subfamily V member 1, the α-2A adrenergic receptor and cholecystokinin B receptor. In conclusion, a temporary disruption of the gut microbiota in early-life results in very specific and long-lasting changes in visceral sensitivity in male rats, a hallmark of stress-related functional disorders of the brain-gut axis such as irritable bowel disorder.
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In the mammalian cerebellum, deep cerebellar nuclear (DCN) cells convey all information from cortical Purkinje cells (PCs) to premotor nuclei and other brain regions. However, how DCN cells integrate inhibitory input from PCs with excitatory inputs from other sources has been difficult to assess, in part due to the large spatial separation between cortical PCs and their target cells in the nuclei. To circumvent this problem we have used a Cre-mediated genetic approach to generate mice in which channelrhodopsin-2 (ChR2), fused with a fluorescent reporter, is selectively expressed by GABAergic neurons, including PCs. ⋯ If bursts of such brief light pulses are delivered, a fixed pattern of bistable bursting emerges. If these pulses are delivered continuously to a spontaneously bistable cell, the immediate response to such photostimulation is inhibitory in the cell's depolarized state and excitatory when the membrane has repolarized; a less regular burst pattern then persists after stimulation has been terminated. These results indicate that the spiking activity of DCN cells can be bidirectionally modulated by the optically activated synaptic inhibition of cortical PCs.
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While estrogens are known to play a crucial role in the neurogenesis of the mammalian and avian brain, their role in teleost adult proliferation pattern is not yet fully understood. The present study aimed to determine the estrogen effects in adult brain proliferation zones, using zebrafish, as a model organism. Indeed, teleost fish brain provides a unique adult neurogenesis model, based on its extensive proliferation, contrasting the restricted adult telencephalic neurogenesis observed in birds and mammals. ⋯ The majority of the BrdU-labeled cells were found to co-express PCNA proliferating marker in Hc, Hv and Vv. Additionally, a population of proliferating cells co-expressed the early neuronal marker TOAD in all areas studied. These results provide significant evidence on the 17-β estradiol impact on adult neurogenesis, down-regulating the fast-cycling and post-mitotic cells within the female zebrafish brain neurogenetic zones.
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Previous studies found that prostaglandins in skeletal muscle play a role in evoking the exercise pressor reflex; however the role played by prostaglandins in the spinal transmission of the reflex is not known. We determined, therefore, whether or not spinal blockade of cyclooxygenase (COX) activity and/or spinal blockade of endoperoxide (EP) 2 or 4 receptors attenuated the exercise pressor reflex in decerebrated rats. We first established that intrathecal doses of a non-specific COX inhibitor Ketorolac (100 μg in 10 μl), a COX-2-specific inhibitor Celecoxib (100 μg in 10 μl), an EP2 antagonist PF-04418948 (10 μg in 10 μl), and an EP4 antagonist L-161,982 (4 μg in 10 μl) effectively attenuated the pressor responses to intrathecal injections of arachidonic acid (100 μg in 10 μl), EP2 agonist Butaprost (4 ng in 10 μl), and EP4 agonist TCS 2510 (6.25 μg in 2.5 μl), respectively. ⋯ We found that Ketorolac significantly attenuated the pressor response to static contraction (before Ketorolac: 23 ± 5 mmHg, after Ketorolac 14 ± 5 mmHg; p<0.05) whereas Celecoxib had no effect. We also found that 8 μg of L-161,982, but not 4 μg of L-161,982, significantly attenuated the pressor response to static contraction (before L-161,982: 21 ± 4 mmHg, after L-161,982 12 ± 3 mmHg; p<0.05), whereas PF-04418948 (10 μg) had no effect. We conclude that spinal COX-1, but not COX-2, plays a role in evoking the exercise pressor reflex, and that the spinal prostaglandins produced by this enzyme are most likely activating spinal EP4 receptors, but not EP2 receptors.
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The pathophysiological processes implicated in ischemic brain damage are strongly affected by an inflammatory reaction characterized by activation of immune cells and release of soluble mediators, including cytokines and chemokines. The pro-inflammatory cytokine interleukin (IL)-1β has been implicated in ischemic brain injury, however, to date, the mechanisms involved in the maturation of this cytokine in the ischemic brain have not been completely elucidated. We have previously suggested that matrix metalloproteinases (MMPs) may be implicated in cytokine production under pathological conditions. ⋯ At this early stage, we observe increased expression of IL-1β in pericallosal astroglial cells and in cortical neurons and this latter signal colocalizes with elevated gelatinolytic activity. By gel zymography, we demonstrate that the increased gelatinolytic signal at 1-h reperfusion is mainly ascribed to MMP2. Thus, MMP2 seems to contribute to early brain elevation of IL-β after transient ischemia and this mechanism may promote damage since pharmacological inhibition of gelatinases by the selective MMP2/MMP9 inhibitor V provides neuroprotection in rats subjected to transient MCAo.