[Show abstract][Hide abstract] ABSTRACT: Neonatal hypoxic-ischemic encephalopathy (HIE) is a major cause of neurological disability requiring newer therapeutic strategies. Uridine is the principal circulating pyrimidine in humans and a substrate for nucleotides and membrane phospholipids. The objective of this study was to investigate the effects of uridine in a neonatal rat model of HIE. Rat pups subjected to hypoxic-ischemic insult on postnatal day 7 were injected intraperitoneally with either saline or uridine (100, 300 or 500mg/kg) for three consecutive days and brains were collected for evaluation of brain infarct volume and apoptosis. Compared with control group, uridine at 300 and 500mg/kg doses significantly reduced percent infarct volume, TUNEL(+) cell ratio and active Caspase-3 immunoreactivity in the cortex, as well as in CA1 and CA3 regions of the hippocampus. Uridine (300 and 500mg/kg) also decreased active Caspase-3 expression in the ipsilateral hemisphere. These data indicate that uridine dose-dependently reduces brain injury in a rat model of neonatal HIE by decreasing apoptosis.
[Show abstract][Hide abstract] ABSTRACT: Orexin neurons are localized in the lateral hypothalamus and regulate many functions including sleep-wake states. Substantial number of neurotransmitters and neuromodulators has been proposed to influence orexinergic system. Glutamate, as the major excitatory amino acid neurotransmitter in the hypothalamus, was shown to mediate orexin neurons in the regulation of wakefulness and feeding. Glutamate is readily present in the lateral hypothalamus, and glutamate receptors are expressed by the neurons of this region. Glutamate agonists initiate excitatory postsynaptic currents in orexin neurons, and this can be blocked by specific antagonists of the glutamate receptors. It is reported that both NMDA and non-NMDA receptors contribute the glutamatergic neurotransmission which affects orexinergic functions. Glutamatergic axon terminals are demonstrated to make contacts with the orexin neurons, as revealed by the presence of vesicular glutamate transporter proteins in the terminals, and these contacts were ultrastructurally confirmed to establish synapses on orexin neurons. This chapter reviews the literature on the glutamatergic regulation of orexin neurons including the data from our laboratory.
[Show abstract][Hide abstract] ABSTRACT: Orexin neuropeptides participate in the regulation of feeding as well as the regulation and maintenance of wakefulness and the cognitive functions. Orexin A and B share a common precursor, prepro-orexin and neurons are localized in the lateral hypothalamus. Physiological studies showed that these neurons are regulated by glutamatergic innervations. We aimed to assess the effects of kainic acid as a potent agonist for non-NMDA glutamate receptors in the activation of orexin neurons. We also analyzed the effect of glutamate antagonist CNQX, injected prior to kainic acid, on this activation. Expression of c-Fos protein was used as a marker for neuronal activation. Dual immunohistochemical labeling was performed for prepro-orexin and c-Fos and the percentages of c-Fos-expressing orexin neurons were obtained for control, kainic acid, and CNQX groups. Kainic acid injection caused statistically significant increase in the number of c-Fos-positive neurons when compared to control group (62.69 and 36.31%, respectively). Activation of orexin neurons was blocked, in part, by CNQX (43.36%). In the light of these results, it is concluded that glutamate takes part in the regulation of orexin neurons and partially exerts its effects through non-NMDA glutamate receptors and that orexin neurons express functional non-NMDA receptors.
[Show abstract][Hide abstract] ABSTRACT: Glutamate is the major excitatory neurotransmitter in the hypothalamus, which exerts its effects by activating ion channel-forming (ionotropic) or G-protein-coupled (metabotropic) receptors. Kainate-preferring glutamate receptor subunits (GluR5, GluR6, GluR7, KA1, and KA2) form one of the three ionotropic receptor families. In the present study, we analyzed the distribution of GluR5 subunit protein in the rat hypothalamus with immunohistochemistry. GluR5 immunoreactivity was observed in perikarya and processes of many hypothalamic cells some of which, based upon their morphological differentiation by size and structure, appeared to be neurons and others glial cells. Analyses revealed that higher number of glial cells were GluR5 positive when compared to the moderate number of GluR5-labeled neurons in the anteroventral periventricular nucleus. Numerous GluR5-expressing neurons and similar number of glia were detected in the suprachiasmatic nucleus. In the arcuate nucleus more glial cells were identified with GluR5 immunoreactivity than the number of labeled neurons. Scattered GluR5-positive cells were present in the periventricular nucleus. Specific immunostaining was not seen in the ventromedial nucleus or dorsomedial nucleus. In conclusion, it is suggested that the GluR5 subunits participate in the glutamatergic regulation of several neuroendocrine systems, such as the tubero-infundibular systems as well as in the control of circadian output through neuron-to-neuron and/or neuron-to-glia interactions.
Molecular Brain Research 06/2005; 136(1-2):38-44. · 2.00 Impact Factor