Biomedical subjects

J T Qiao

Publications and source records attributed to J T Qiao.

At least 19 recordsLinked to original sources

PubMed2001

Opiate-like substances mediate norepinephrine-induced but not serotonin-induced antinociception at spinal level: reevaluation by an electrophysiological model of formalin test in rats.

After subcutaneous injection of formalin (5%, 50 microl) into a hindpaw of rats, biphasic excitatory nociceptive discharges were recorded extracellularly in thalamic parafascicular neurons. Intrathecal (i.t.) administration of either norepinephrine (NE. 6 nmol, 10 microl) or serotonin (5-HT, 120 nmol, 10 microl) prior to the second phase significantly inhibited the second phase of the formalin-induced parafascicular nociceptive discharges. Intrathecal naloxone (Nal, 50 nmol, 10 microl) did not show any effect on the parafascicular nociceptive discharges. However, when i.t. Nal was given 5 min before NE, Nal prevented the NE antinociceptive effect. Pre-administration of Nal before 5-HT did not affect the antinociceptive effects of 5-HT on the second phase of nociceptive discharges. These results indicate that opiate-like substances are involved in the mediation of NE-induced antinociception. It is suggested that endogenous NE and 5-HT released from brainstem descending terminals at the spinal level carry out their antinociceptive actions differently.

Animals↗

PubMed2001

Long-term potentiation in hippocampus of rats is enhanced by endogenous acetylcholine in a way that is independent of N-methyl-D-aspartate receptors.

By using extracellular recordings of field potential, the exact pathway by which the endogenous ACh influencing the induction of long-term potentiation (LTP) in CA1 area was analysed in slices of rat hippocampus. The results showed that: (1) the application of (-) huperzine A, an AChE inhibitor extracted from Chinese herb Qian Ceng Ta (Huperzia Serrata), could enhance the induction of LTP, while this drug showed little effect on the second components of multiple population spikes that were recorded in Mg(2+)-free medium and had proven to be N-methyl-D-aspartate (NMDA) receptor-mediated response; and (2) scopolamine, a muscarinic receptor antagonist, could significantly suppressed the induction of LTP, while most of the suppressive effect of scopolamine was blocked when slices were pretreated by bicuculline, a gamma-aminobutyric acid (GABA(A)) receptor antagonist. These results suggest that endogenous ACh potentiates the induction of LTP through the inhibition of GABAergic interneurons that modulate pyramidal neurons, but not through the activation of NMDA receptors located on pyramidal neurons.

Acetylcholine↗

PubMed2001

Amyloid beta-protein fragment 31-35 forms ion channels in membrane patches excised from rat hippocampal neurons.

Inside-out membrane patches excised from rat hippocampal neurons were used to test if ion channels could be formed by fragment 31-35 of amyloid beta-protein. The results showed: (1) after application of fragment 31-35 of amyloid beta-protein (5 microM) to either the inner or outer side of the patches, spontaneous currents could be recorded from those patches that had previously been 'silent'; (2) the fragment 31-35-induced conductance was cation-selective with a permeability ratio of P(Cs)/P(Cl)=23; (3) different levels of conductance, ranging from 25 to 500 pS, could be recorded in different patches, and in some cases, different conductances and spontaneous transitions among them could be recorded in a single patch; and (4) application of ZnCl(2) (1 mM) to the inner side of the patches reversibly blocked the newly formed channel activity; a similar effect was observed after application of CdCl(2) (1 mM). These results show that fragment 31-35 of amyloid beta-protein can insert into membrane patches from both sides and form cation-selective, Zn(2+)- and Cd(2+)-sensitive ion channels. It is proposed that fragment 31-35 in amyloid beta-protein might be the shortest active sequence known to date to form ion channels across neuronal membranes.

Amyloid beta-Peptides↗

PubMed2001

Suppression of large conductance Ca2+-activated K+ channels by amyloid beta-protein fragment 31-35 in membrane patches excised from hippocampal neurons.

To clarify the shortest essential active sequence in amyloid beta-protein (AbetaP) responsible for affecting neuronal electrophysiological properties, the effects of fragments 31-35 and 25-35 of AbetaP on the large conductance Ca(2+)-activated potassium (BK) channels were investigated in the "inside-out" membrane patches excised from hippocampal neurons of rats. After application of AbetaP 3l-35 (5 micromol/L, n=10), the mean P(o) and open frequency of BK channels decreased by 85.8+/-l3.5 percent;percent; (P<0.01) and 72.1+/-22.8 percent; (P<0.01), respectively, and the mean open time decreased by 41.l+/-l8.5 percent; (P<0.0l), while the mean current amplitude was not significantly affected (P>0.05). Application of AbetaP 25-35 (5 micromol/L) also induced a decrease of 85.5+/-22.l percent; (P<0.0l) in mean P(o) and of 5l.4+/-18.3 percent; (P<0.05) in mean open time within l~3 min after application. These results suggest that the functional alteration in BK channels elicited by AbetaP fragments may play an important role in the mechanisms underlying AbetaP neurotoxicity, and AbetaP 31-35 may be the shortest active sequence in AbetaP responsible for affecting the electrophysiological properties of neurons.

Amyloid beta-Peptides↗

PubMed2000

Norepinephrine modulates single hypothalamic arcuate neurons via alpha(1)and beta adrenergic receptors.

The effects of norepinephrine (NE) on the electrophysiological activities of single hypothalamic arcuate neurons were studied using extracellular recording of 385 neurons from 169 brain slices in rats. The results showed that: (1) of 236 neurons selected randomly and tested with NE application, 137 (58.0%) were excited, 67 (28.4%) were inhibited, and 32 (13.6%) failed to respond; (2) substitution of low Ca(2+)-high Mg(2+) artificial cerebrospinal fluid (ACSF) for normal ACSF abolished the NE-induced inhibitory effect but failed to abolish the excitatory effect; (3) both the NE-induced excitatory and inhibitory effects were antagonized partly by phentolamine, prazosin, and propranolol but not by yohimbine; (4) naloxone and glibenclamide, a blocker of adenosine triphosphate-sensitive (K(ATP)) channels, blocked the NE-induced inhibitory effect; and (5) neurons that were inhibited by NE were also inhibited by morphine and cromakalim, an agonist of K(ATP) channels, and moreover, the morphine-induced inhibitory effect could be blocked by glibenclamide, while the cromakalim-induced inhibitory effect was not blocked by naloxone. These results imply that: (a) NE excites arcuate neurons through a mechanism that is insensitive to lowering the extracellular Ca(2+) suggesting a direct postsynaptic response through alpha(1)- and beta-adrenergic receptors, while NE inhibits cells through at least an inhibitory interneuron in arcuate and so is dependent on a Ca(2+)-sensitive presynaptic release mechanism; and (b) the inhibitory interneuron may be opioidergic, being excited first through alpha(1)- and beta-adrenergic receptors, after which the released opioids inhibit the neurons being recorded with an involvement of activation of K(ATP) channels. This possibility needs to be substantiated in much more detail.

Action Potentials↗

PubMed2000

Neurokinin A, calcitonin gene-related peptide, and dynorphin A (1-8) in spinal dorsal horn contribute to descending inhibition evoked by nociceptive afferent pathways: an immunocytochemical study.

Immunocytochemical technique was used to compare the contents of neurokinin A (NKA), calcitonin gene-related peptide (CGRP), and dynorphin A (1-8) (DynA) on two sides of the lumbar dorsal horn of rats in which the unilateral thoracic dorsalateral funiculus (DLF) was transected while formalin (0.2 ml, 0.5%) was injected equally into two hindpaws. The results showed that all the NKA-like, CGRP-like, and DynA (1-8)-like immunoreactivities were significantly lower in the superficial laminae of the dorsal horn on the side ipsilateral to the lesioned DLF than that on the side with intact DLF. This implies that peripheral noxious inputs activate the supraspinal descending inhibitory systems which in turn modulate the transmission of noxious message at the spinal level by changing the release of related neuropeptides.

Afferent Pathways↗

PubMed1999

Suppressive action produced by beta-amyloid peptide fragment 31-35 on long-term potentiation in rat hippocampus is N-methyl-D-aspartate receptor-independent: it's offset by (-)huperzine A.

Extracellular recordings of field potential from CA1 region of rat hippocampal slices were used to observe the effects of a shorter synthetic fragment of beta-amyloid peptide (A beta31-35) on the induction of long-term potentiation (LTP) and the action of (-)huperzine A, a potent acetylcholinesterase (AChE) inhibitor on these processes was also observed. The results showed that: (1) 0.1 microM A beta31-35 suppressed the induction of LTP in a similar mode as the longer fragment A beta25-35, did, while they did not change the amplitude of the baseline population spike (PS); (2) when PSs were recorded separately in Mg2+-free medium, which unveils the N-methyl-D-aspartate (NMDA)-mediated responses, both A beta31-35 and A beta25-35 showed little effect on the components of multiple PSs; (3) two concentrations of 0.1 microM or 1.0 microM (-)huperzine A showed no effects on the PS amplitude while the latter could enhance the LTP and (4) co-administration of (-)huperzine A with 0.1 microM concentration could block most of the suppressive action induced by A beta31-35 or A beta25-35 upon the LTP. The results suggest that the shorter fragment A beta31-35, is long enough to suppress the induction of LTP and these two fragments might suppress the induction of LTP through a NMDA receptor-independent pathway that involves cholinergic terminals in hippocampus.

Alkaloids↗

PubMed1999

Peripheral nitric oxide contributes to both formalin- and NMDA-induced activation of nociceptors: An immunocytochemical study in rats.

Nociceptive c-fos expressions in the dorsal horn following intraplantar injection of two kinds of algogenic agents combined with different doses of nitric oxide (NO) synthase inhibitor (N(omega)-nitro-L-arginine methyl ester (L-NAME)) or of NO donor (L-arginine) were used to explore if NO was involved in the activation of peripheral nociceptors. The results showed that: 1) combined injections of L-NAME with formalin into the plantar aspect of one hindpaw of normal rats elicited a dose-dependent suppression of c-fos expression as compared to that induced by formalin alone; 2) combined injections of L-arginine with formalin elicited considerable enhancement of c-fos expression when the dosages of L-arginine were less than 20 micromol, while it elicited marked suppression of c-fos expression when the dosages were in the range from 50 to 100 micromol; and 3) combined injection of L-NAME with NMDA, a selective agonist for NMDA receptors, into the hindpaw could also inhibit the NMDA-induced c-fos expression in the spinal dorsal horn. These results suggest that endogenously generated concentrations of nitric oxide may enhance the initiation of nociceptive inputs of peripheral nociceptors following local injection of formalin or NMDA.

Animals↗

PubMed1999

Interrelations of opioids with monoamines in descending inhibition of nociceptive transmission at the spinal level: an immunocytochemical study.

This study was designed to reexamine a previous proposal of whether the opioid-like substances (OLS) being acting mainly as an intrinsic spinal mediator in the descending inhibition of nociception of the bulbospinally projecting NE-ergic, and/or 5-HT-ergic terminals in the dorsal horn by using an immunocytochemical method. The effects of intrathecal (i.t.) phentolamine (Ph), cyproheptadine (Cyp), and naloxone (Nal), administered separately or coadministered by two of them, on the expression of Fos-like-immunoreactive (FLI) neurons were observed on both sides of the lumbar dorsal horn of rats, in which equal volumes of formalin were injected into two hindpaws and the ipsilateral dorsolateral funiculus (DLF) was transected at the thoracic level antecedently. The results showed: (1) when rats were pretreated with i.t. saline, the number of nociceptive FLI neurons was significantly lowered 44% (p<0.01) on the side of the lumbar dorsal horn with intact DLF compared to the opposite side with sectioned DLF; (2) when rats were separately pretreated with i.t. Ph, Cyp and Nal, the reduction of FLI neurons on the DLF-intact side were decreased by 27% (p<0.01), 21% (p<0.01), and 25% (p<0.01), respectively; (3) when rats were pretreated with combined i.t. Ph+Cyp, the reduction on the intact side was eliminated almost completely (4%); (4) when rats were pretreated with combined i.t. Ph+Nal, the reduction on the intact side was 21% (p<0.01); and (5) when rats were pretreated with i.t. Cyp+Nal, the reduction on the intact side was 9.1%. These results suggest that: (1) nearly all the suppressive action exerted by the DLF-descending fibers are produced by the release of either NE or 5-HT as neurotransmitters at the spinal level; (2) most of the opioid-like substances act as an intrinsic spinal mediator mainly for the descending NE-ergic, but in a lesser extent for the 5-HT-ergic terminals in the dorsal horn circuitry; and (3) some OLS-ergic interneurons may only be activated by local nociceptive input.

Adrenergic alpha-Antagonists↗

PubMed1999

Decreased expression of N-methyl-D-aspartate (NMDA) receptors in rat dorsal root ganglion following complete Freund's adjuvant-induced inflammation: an immunocytochemical study for NMDA NR1 subunit.

The changes in expression of NMDA NR1, an essential functional subunit of N-methyl-D-aspartate (NMDA) receptors, were examined in the rat lumbar dorsal root ganglion (DRG) by immunocytochemical technique following injection of complete Freund's adjuvant (CFA) into the unilateral hindpaw. The results showed that there appeared a significant and several days-lasting down-regulation in expression of NMDA NR1 in the lumbar DRG following CFA injection, and especially, this change mainly appeared in the small and medium sized DRG neurons. It is suggested that a long-lasting flow of nociceptive inputs in nociceptors will elicit a decreased expression of NMDA receptors on primary afferent neurons and this plastic change would act as a factor leading towards the hyposensitization for nociception at the nociceptor level.

Animals↗

PubMed1999

Endogenous adenosine involved in the mediation of spinal antinociception produced by stimulating locus coeruleus.

The focus of this study was to investigate whether spinal adenosine is involved in mediating descending nociceptive modulation by the locus coeruleus (LC). Nociceptive evoked responses in parafascicular (PF) neurons were studied before and after electrical stimulation of the LC as well as before and after intrathecal (i.t.) administration of phentolamine (Ph) or aminophylline (Aph), an adenosine receptor antagonist, and 5'ethylcarboxamidoadenosine (NECA), an adenosine agonist. The main results were as follows: (1) the nociceptive evoked responses recorded in PF neurons were suppressed by LC stimulation; (2) pretreatment with i.t., Ph (40 nmol) reversed the LC effects, i.e., the suppressive effect of LC stimulation on the PF nociceptive evoked responses was reversed in the presence of Ph; (3) smaller doses of i.t. Aph (120 nmol) blocked only the suppressive effect produced by LC stimulation, while larger doses (240 nmol) reversed the LC stimulation, i.e., the LC stimulation exerted a facilatatory effect; and (4) i.t. application of NECA, an adenosine agonist, suppressed the nociceptive discharges in PF neurons. The results suggest that spinal adenosine may be involved in the mediation of the spinal antinociceptive effect produced by LC stimulation.

Adenosine↗

PubMed1999

Beta-amyloid peptide fragment 31-35 induces apoptosis in cultured cortical neurons.

A synthetic fragment 31-35 of beta-amyloid peptide was used in cultured cortical neurons to examine whether this smaller sequence could trigger apoptotic degeneration in vitro by using morphological, biochemical and flow-cytometric examinations. The results showed that: (i) neurons treated with fragment 31-35 of beta-amyloid peptide exhibited membrane blebbing, compaction of nuclear chromatin, nuclear shrinkage and nuclear fragmentation; (ii) a typical DNA ladder was revealed by agarose gel electrophoresis following fragment 31-35 of beta-amyloid peptide exposure; (iii) the internucleosome DNA fragmentation was also detected by flow-cytometric examination following fragment 31-35 of beta-amyloid peptide exposure; and (iv) the DNA fragmentation induced by fragment 31-35 of beta-amyloid peptide in the above two examinations could be blocked by co-treatment with aurintricarboxylic acid or actinomycin D. It is suggested that fragment 31-35 of the beta-amyloid peptide may be a shorter sequence of beta-amyloid peptide responsible for triggering an apoptotic process in cultured neurons.

Amyloid beta-Peptides↗

PubMed1999

Involvement of endogenous opioids and ATP-sensitive potassium channels in the mediation of apomorphine-induced antinociception at the spinal level: a study using EMG planimetry of flexor reflex in rats.

The effects of intrathecally (i.t.) administered naloxone or glibenclamide, a blocker of adenosine triphosphate-sensitive potassium (KATP) channels, on the antinociception produced by i.t. apomorphine were observed by an integrated electromyogram measurement of hindlimb flexor reflex in lightly pentobarbital-anesthetized rats. The results showed that i.t. apomorphine produced a significant and dose-dependent antinociception and that the antinociception produced by i.t. apomorphine could be blocked dose dependently by i.t. naloxone or glibenclamide. The results suggest that endogenous opioids and ATP-sensitive potassium channels might be sequentially involved in the mediation of apomorphine-induced antinociception at the spinal level.

Adenosine Triphosphate↗

PubMed1999

[A quantitative study on the synaptic ultrastructural alterations in visual cortex in the maintenance of LTP].

The ultrastructure of synapses three hours after formation of long-term potentiation (LTP) was examined in the local microslices of visual cortical brain slices of 18-20 d rats. Slices without potentiating stimulation which were similarly incubated served as controls. The following structural changes were examined using a graph analyzer: (1) synaptic cleft width; (2) thickness of the postsynaptic densities(PSD); (3) length of the active zones; and (4) curvature of the synaptic interface. The number of synapses of different types in layer II/III of visual cortex was quantified by double-blind scoring procedures. The various counts were converted to the number of synapses per unit volume using stereological quantitation method. Analysis of variance was used for statistical evaluation. Our results suggest that field potentials reached their peak values at about one and a half hours after tetanus and could be maintained as long as three hours without decay. In comparison with the control groups, synaptic cleft width, thickness of PSD, surface density per unit volume(Sv) of the active zones, curvature of the synaptic interface, numeric density per unit volume (Nv) of all synapses, spine synapses and the Nv of perforated synapses were all increased significantly. These data suggest that the increase of Sv of active zones and the increase of the curvature of synaptic interface may be the morphological feature characterizing the maintenance of LTP, in addition to the formation of perforated synapses.

Animals↗

PubMed1998

c-Fos expression in NMDA receptor-contained neurons in spinal cord in a rat model of inflammation: a double immunocytochemical study.

Double-labeling techniques were used to demonstrate the nociceptive activation of NMDA receptor-contained neurons in spinal dorsal horn by using c-Fos immunoreactivity as an indicator of this activation in a rat model of inflammation. About 25% and 55% of the c-Fos-immunoreactive neurons that were found in laminae I-II and lamina V showed NMDA receptor immunoreactivity, while about 4% and 11% of NMDA-receptor immunoreactive neurons in these two regions showed c-Fos immunoreactivity, respectively. The implication of the results was discussed.

Animals↗

PubMed1998

Locus coeruleus modulates thalamic nociceptive responses via adrenoceptors.

This study investigated the parafascicular (PF) neuronal nociceptive responses and their modulation following electrical stimulation of the locus coeruleus (LC) and intrathecal (i.t.) or intracerebroventricular (i.c.v.) administration of two alpha-adrenoceptor antagonists, the alpha2-antagonist, yohimbine, and the alpha1-antagonist, prazosin. The main results were as follows: (1) the nociceptive evoked discharges in PF neurons were suppressed by preceding stimulation of LC; (2) the suppressive effect of LC stimulation on PF neurons was replaced by a facilitatory effect following pretreatment of i.t. yohimbine in 14 units tested, while i.t. prazosin failed to alter the LC-induced suppression, even when the prazosin dose was doubled; (3) i.c.v. pretreatment with prazosin strengthened the suppressive effect of LC stimulation on PF neurons; (4) i.c.v. norepinephrine (NE) administration induced, in PF neurons, a biphasic response to noxious stimulation; an early, brief (about 10 min) inhibitory effect followed by a late, long-lasting facilitatory effect; and (5) i.c.v. pretreatment of yohimbine or prazosin prevented the inhibitory or facilitatory responses released by NE, respectively. These results provide evidence that: (1) the LC-descending projections exhibit a suppressive effect on nociceptive transmission at the spinal level through alpha2-receptors; and (2) the LC-ascending projections exhibit dual effects, facilitatory and inhibitory, at the medial thalamus (PF) level through alpha1- and alpha2-receptors, respectively.

Adrenergic alpha-Agonists↗

PubMed1998

Pre-emptive intrathecal Mk-801, a non-competitive N-methyl-D-aspartate receptor antagonist, inhibits the up-regulation of spinal dynorphin mRNA and hyperalgesia in a rat model of chronic inflammation.

The effects of N-methyl-D-aspartate(NMDA) receptor antagonist, Mk-801, on the expression of spinal dynorphin (DYN) mRNA and the hyperalgesia induced by peripheral inflammation were studied by Northern analysis and behavioral test. Following an unilateral injection of complete Freund's adjuvant (CFA) into the rat hindpaw, there appeared a significant hyperalgesia of inflamed hindpaw and up-regulation of ipsilateral spinal DYN mRNA; while the pre-emptive and continuous intrathecal administration of Mk-801 (10 microg/microl per h) could significantly suppress both the hyperalgesia and the up-regulation of spinal DYN mRNA induced by peripheral inflammation. The results suggest that NMDA receptor activation may contribute to the development and maintenance of the thermal hyperalgesia that is associated with the up-regulation of DYN expression in spinal dorsal horn.

Animals↗

PubMed1998

Nitric oxide contributes to both spinal nociceptive transmission and its descending inhibition in rats: an immunocytochemical study.

The present study was designed to determine if nitric oxide (NO) was involved both in the dorsal horn responses to the primary nociceptive inputs and the descending inhibitory action on these responses. The first part of the experiments showed that when formalin was injected into one hindpaw, the nociceptive c-fos expression in the lumbar dorsal horn ipsilateral to the injection was suppressed dose-dependently by intrathecal (i.t.) administration of Nomega-nitro-L-arginine (L-NNA), a nitric oxide synthase inhibitor. In the second part of the study, the formalin injection was carried out into two hindpaws of the rats with a sectioned dorsal quadrant at the thoracic spinal level, in these rats, there was a significant suppression of c-fos expression in the dorsal horn on the side with intact dorsal quadrant, reasonably owing to the preservation of the spinally descending inhibitory fibers from the supraspinal level; furthermore, this suppression could be canceled following i.t. L-NNA administration. The results suggest that endogenous NO not only facilitates the perception of nociceptive inputs at the spinal level but also enhances the descending inhibition upon the spinal nociception.

Animals↗