Neuroscience
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Glutamine plays multiple roles in the CNS, including metabolic functions and production of the neurotransmitters glutamate and GABA. It has been proposed to be taken up into neurons via a variety of membrane transport systems, including system A, which is a sodium-dependent electrogenic amino acid transporter system. In this study, we investigate glutamine transport by application of amino acids to individual principal neurons of the medial nucleus of the trapezoid body (MNTB) in acutely isolated rat brain slices. ⋯ Additionally, we examined the expression of different system A transporter isoforms using immunocytochemical staining with antibodies raised against system A transporter 1 and 2 (SAT1 and SAT2). Our results indicate that both isoforms are expressed in MNTB principal neurons, and demonstrate that functional system A transporters are present in the plasma membrane of neurons. Since system A transport is highly regulated by a number of cellular signaling mechanisms and glutamine then goes on to activate other pathways, the study of these transporters in situ gives an indication of the mechanisms of neuronal glutamine supply as well as points of regulation of neurotransmitter production, cellular signaling and metabolism in the native neuronal environment.
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Following CNS injury there is a period of vulnerability when cells will not easily tolerate a secondary insult. However recent studies have shown that following traumatic brain injury (TBI), as well as hypoxic-ischemic injuries, the CNS may experience a period of protection termed "preconditioning." While there is literature characterizing the properties of vulnerability and preconditioning in the adult rodent, there is an absence of comparable literature in the developing rat. To determine if there is a window of vulnerability in the developing rat, post-natal day 19 animals were subjected to a severe lateral fluid percussion injury followed by pilocarpine (Pc)-induced status epilepticus at 1, 6 or 24 h post TBI. ⋯ Instead of producing a state of hippocampal vulnerability to activation, TBI produced a state of neuroprotection. However, in a second group of animals evaluated 20 weeks post injury, double-injured animals were statistically indistinguishable in terms of seizure threshold, mossy fiber sprouting and cell survival when compared to those treated with Pc alone. TBI, therefore, produced a temporary state of neuroprotection from seizure-induced cell death in the developing rat; however, this ultimately conferred no long-term protection from altered hippocampal circuit rearrangements, enhanced excitability or later convulsive seizures.
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Pertussis toxin (PTX) treatment results in ADP-ribosylation of Gi-protein and thus in disruption of mu-opioid receptor signal transduction and loss of the antinociceptive effect of morphine. We have previously demonstrated that pretreatment with ultra-low dose naloxone preserves the antinociceptive effect of morphine in PTX-treated rats. The present study further examined the effect of ultra-low dose naloxone on mu-opioid receptor signaling in PTX-treated rats and the underlying mechanism. ⋯ In addition to the anti-neuroinflammatory effect and glutamate transporter modulation previously observed in PTX-treated rats, the re-establishment of mu-opioid receptor Gi/Go-protein coupling is involved in the restoration of the antinociceptive effect of morphine by ultra-low dose naloxone pretreatment by normalizing the balance between the excitatory and inhibitory signaling pathways. These results show that ultra-low dose naloxone preserves the antinociceptive effect of morphine, suppresses spinal neuroinflammation, and reduces PTX-elevated excitatory Gs-coupled opioid receptors in PTX-treated rats. We suggest that ultra-low dose naloxone might be clinically valuable in pain management.
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Orexin-A, synthesized by neurons of the lateral hypothalamus helps to maintain wakefulness through excitatory projections to nuclei involved in arousal. Obvious changes in eye movements, eyelid position and pupil reactions seen in the transition to sleep led to the investigation of orexin-A projections to visuomotor cell groups to determine whether direct pathways exist that may modify visuomotor behaviors during the sleep-wake cycle. Histological markers were used to define these specific visuomotor cell groups in monkey brainstem sections and combined with orexin-A immunostaining. ⋯ In contrast, the motoneurons supplying the multiply-innervated muscle fibers of the extraocular muscles, the motoneurons of the levator palpebrae muscle in the central caudal nucleus, and especially the preganglionic neurons supplying the ciliary ganglion received a strong orexin input. We interpret these results as evidence that orexin-A does modulate pupil size, lid position, and possibly convergence and eye alignment via the motoneurons of multiply-innervated muscle fibres. However orexin-A does not directly modulate premotor pathways for saccades or the singly-innervated muscle fibre motoneurons.
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Isoflurane preconditioning improved short-term neurological outcome after focal brain ischemia in adult rats. It is not known whether desflurane induces a delayed phase of preconditioning in the brain and whether isoflurane preconditioning-induced neuroprotection is long-lasting. Two months-old Sprague-Dawley male rats were exposed to or were not exposed to isoflurane or desflurane for 30 min and then subjected to a 90 min middle cerebral arterial occlusion (MCAO) at 24 h after the anesthetic exposure. ⋯ We conclude that isoflurane preconditioning improves short-term and long-term neurological outcome and reduces delayed cell death after transient focal brain ischemia in adult rats. Bcl-2 may be involved in the isoflurane preconditioning effect. Desflurane pretreatment did not induce a delayed phase of neuroprotection.