Neuroscience
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Comparative Study
Changes in peptidyl-prolyl cis/trans isomerase activity and FK506 binding protein expression following neuroprotection by FK506 in the ischemic rat brain.
FK506 is an immunosuppressant also showing neuroprotection following cerebral ischemia. FK506 binds to intracellular proteins (FKBP) which have a wide range of functions but have in common the peptidyl-prolyl cis/trans isomerase activity. Following transient focal ischemia, we have analyzed the expression of FKBP12, 52 and 65 and the total FKBP enzyme activity. ⋯ Cerebral ischemic damage to the brain was reduced by FK506. It was shown for the first time that neuroprotection by FK506 also included the suppression of the cerebral peptidyl-prolyl cis/trans isomerase activity of FKBP in vivo whereas the expression levels of FKBP12, 52 and 65 following ischemia changed slightly and FK506 treatment does not suppress the expression patterns. However, changes of FKBP enzymatic activity result in suppression of the stress cell body response in the peri-infarct area as observed by suppression of c-Jun phosphorylation and Fas-L expression.
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P2X receptors are non-selective cation channels gated by extracellular ATP and are encoded by a family of seven subunit genes in mammals. These receptors exhibit high permeabilities to calcium and in the mammalian nervous system they have been linked to modulation of neurotransmitter release. Previously, three complementary DNAs (cDNAs) encoding members of the zebrafish gene family have been described. ⋯ Analysis of gene expression patterns was carried out using in situ hybridization, and seven of the nine genes were found to be expressed in embryos at 24 and 48 h post-fertilization. Of the seven that were expressed, six were present in the nervous system and four of these demonstrated considerable overlap in cells present in the sensory nervous system. These results suggest that P2X receptors might play a role in the early development and/or function of the sensory nervous system in vertebrates.
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Comparative Study
Cyclooxygenase 2 in infiltrating inflammatory cells in injured nerve is universally up-regulated following various types of peripheral nerve injury.
We previously reported the up-regulation of cyclooxygenase 2 (COX2) in injured sciatic nerve of rats with partial sciatic nerve ligation (PSNL) and the reversal of PSNL-elicited tactile allodynia by local injection of the COX inhibitor ketorolac [Eur J Neurosci 15 (2002) 1037]. We further asked whether COX2 up-regulation in injured nerve is a universal phenomenon following various types of nerve injury. In the current study, we observed that abundant COX2 immunoreactive (IR) cell profiles appeared in injured nerves of rats following spinal nerve ligation (SNL), chronic constriction injury (CCI) and complete sciatic nerve transection. ⋯ Local ketorolac's anti-allodynia lasted much shorter when given 2-3 months after lesion. Local ketorolac failed to induce anti-allodynia 7 months after lesion, a time when COX2-IR cells completely disappeared from the injured nerve except a few cells at the injury site. Our data strongly suggest that during the initial several months after nerve injury, peripherally over-produced prostaglandins play an important role in the maintenance of neuropathic pain.
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Activation of cannabinoid CB(2) receptors attenuates thermal nociception in untreated animals while failing to produce centrally mediated effects such as hypothermia and catalepsy [Pain 93 (2001) 239]. The present study was conducted to test the hypothesis that activation of CB(2) in the periphery suppresses the development of inflammatory pain as well as inflammation-evoked neuronal activity at the level of the CNS. The CB(2)-selective cannabinoid agonist AM1241 (100, 330 micrograms/kg i.p.) suppressed the development of carrageenan-evoked thermal and mechanical hyperalgesia and allodynia. ⋯ AM1241 suppressed carrageenan-evoked Fos protein expression in the superficial and neck region of the dorsal horn but not in the nucleus proprius or the ventral horn. The suppression of carrageenan-evoked Fos protein expression induced by AM1241 was blocked by coadministration of SR144528 in all spinal laminae. These data provide evidence that actions at cannabinoid CB(2) receptors are sufficient to suppress inflammation-evoked neuronal activity at rostral levels of processing in the spinal dorsal horn, consistent with the ability of AM1241 to normalize nociceptive thresholds and produce antinociception in inflammatory pain states.
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Comparative Study
Sex differences in the hippocampal dentate gyrus of the guinea-pig before puberty.
The aim of the present research was to ascertain the presence of sex differences in the hippocampal dentate gyrus of the guinea-pig, a long-gestation rodent which gives birth to mature young and whose brain is at a more advanced stage of maturation at birth than that of the rat and mouse. The brains of neonatal (15-16 days old) and prepubescent (45-46 days old) male and female guinea pigs were Golgi-Cox stained. Granule cells were sampled from the upper (suprapyramidal) and lower (infrapyramidal) blade of the septal dentate gyrus and their dendritic tree and soma were measured. ⋯ In the lower blade the granule cells showed very few sex differences in both neonatal and prepubescent animals. This study shows wide dynamically changing sex differences in the granule cells located in the upper blade of the septal dentate gyrus, but almost no differences in the lower blade. These results demonstrate that sex differences are not ubiquitous in the dentate gyrus and suggest that the lower blade, unlike the upper blade, might be involved in non-sexually dimorphic behaviors.