Neuroscience
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Comparative Study
The nociceptin receptor antagonist [Nphe1,Arg14,Lys15]nociceptin/orphanin FQ-NH2 blocks the stimulatory effects of nociceptin/orphanin FQ on the HPA axis in rats.
Nociceptin/orphanin FQ (N/OFQ) is an opioid-related peptide that stimulates corticosterone release after i.c.v. administration in non-stressed rats. We employed in situ hybridization histochemistry to investigate N/OFQ-stimulated activation of the HPA axis at the hypothalamic and pituitary level. We have demonstrated that N/OFQ-induced activation of the HPA axis is mediated via the central N/OFQ peptide receptor (NOP) using the recently described selective NOP antagonist [Nphe(1),Arg(14),Lys(15)]nociceptin/orphanin FQ-NH(2) (UFP-101). ⋯ UFP-101 also blocked the N/OFQ-induced increase in CRF mRNA and POMC mRNA. These results demonstrate that centrally administered N/OFQ activates the HPA axis via up-regulation of CRF and POMC mRNA and stimulation of corticosterone release in rats. Further, we have demonstrated for the first time that the selective NOP receptor antagonist UFP-101 blocks these effects indicating that N/OFQ-induced HPA axis activation is mediated via central NOP receptors.
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Comparative Study
Co-localization of glycine and gaba immunoreactivity in interneurons in Macaca monkey cerebellar cortex.
Previous work demonstrates that the cerebellum uses glycine as a fast inhibitory neurotransmitter [Ottersen OP, Davanger S, Storm-Mathisen J (1987) Glycine-like immunoreactivity in the cerebellum of rat and Senegalese baboon, Papio papio: a comparison with the distribution of GABA-like immunoreactivity and with [3H]glycine and [3H]GABA uptake. Exp Brain Res 66(1):211-221; Ottersen OP, Storm-Mathisen J, Somogyi P (1988) Colocalization of glycine-like and GABA-like immunoreactivities in Golgi cell terminals in the rat cerebellum: a postembedding light and electron microscopic study. Brain Res 450(1-2):342-353; Dieudonne S (1995) Glycinergic synaptic currents in Golgi cells of the rat cerebellum. ⋯ The patterns of labeling for glycine and GABA within Golgi and Lugaro cells also indicate that there are biochemical sub-types which are morphologically similar. Further, we find that glycine, GABA and glutamic acid decarboxylase identified candelabrum cells adjacent to the Purkinje cells which is the first time that this interneuron has been reported in primate cerebellar cortex. We propose that candelabrum cells, like the majority of Golgi and Lugaro cells, release both glycine and GABA.
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Neuronal proteins have been traditionally viewed as being derived solely from the soma; however, accumulating evidence indicates that dendritic and axonal sites are capable of a more autonomous role in terms of new protein synthesis. Such extra-somal translation allows for more rapid, on-demand regulation of neuronal structure and function than would otherwise be possible. While mechanisms of dendritic RNA transport have been elucidated, it remains unclear how RNA is trafficked into the axon for this purpose. ⋯ Stau2 and FMRP protein were localized to the sciatic nerve and dorsal roots by immunohistochemistry and to dorsal roots by Western blot. Stau2 and FMRP immunoreactivities colocalized with transient receptor potential channel type 1 immunoreactivity in sensory axons of the sciatic nerve and dorsal root, suggesting that these proteins are being transported into the peripheral and central terminals of nociceptive sensory axons. Based on these findings, we propose that stau2 and FMRP proteins are attractive candidates to subserve RNA transport in sensory neurons, linking somal transcriptional events to axonal translation.
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Hyperpolarization-activated cyclic-nucleotide-gated (HCN) channels conduct a monovalent cationic current, I(h), which contributes to the electrophysiological properties of neurons and regulates thalamic oscillations in circuits containing the glutamatergic ventrobasal complex (VB) and GABAergic reticular thalamic nucleus (RTN). Four distinct HCN channel isoforms (HCN1-4) have been identified, and mRNAs and proteins for HCN channels have been detected in the RTN and VB, with HCN2 and HCN4 being the predominant isoforms. RTN and VB neurons have distinct electrophysiological properties, and those differences may reflect variable compartmental distribution of HCN channels. ⋯ In contrast, HCN4-IR did not colocalize with either synaptophysin or cortactin. The colocalization of HCN2-IR with HCN4-IR was greater in VB than in RTN. The results suggest that the distinct compartmental distribution of HCN2 channels in RTN and VB neurons contributes to the profound differences in the I(h)-dependent properties of these cells.
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Comparative Study
Acute changes in the neuronal expression of GABA and glutamate decarboxylase isoforms in the rat piriform cortex following status epilepticus.
The piriform cortex (PC) is the largest region of the mammalian olfactory cortex with strong connections to other limbic structures, including the amygdala, hippocampus, and entorhinal cortex. In addition to its functional importance in the classification of olfactory stimuli, the PC has been implicated in the study of memory processing, spread of excitatory information, and the facilitation and propagation of seizures within the limbic system. Previous data from the kindling model of epilepsy indicated that alterations in GABAergic inhibition in the transition zone between the anterior and posterior PC, termed here central PC, are particularly involved in the processes underlying seizure propagation. ⋯ One likely explanation for this finding is that remaining GABA neurons in layer II of the central PC maintain high levels of activity to control the increased excitability of the region. In line with previous studies, an up-regulation of GAD67 mRNA, but not GAD65 mRNA, was observed in dentate granule cells following seizures, whereas no indication of such up-regulation was determined for the other brain regions examined. The data substantiate the particular susceptibility of the central PC to seizure-induced plasticity and indicate that this brain region provides an interesting tool to study the regulation of GAD isoenzymes.