Hippocampus quinolinic acid modulates glutamate and NMDAR/mGluR1 in chronic unpredictable mild stress-induced depression / 生理学报

The present study was to investigate the role of the quinolinic acid (QUIN) and its relationship with N-methyl-D-aspartic acid (NMDA) receptor and metabotropic glutamate receptor 1 (mGluR1) in depression induced by chronic unpredictable mild stress (CUMS) in hippocampus. CUMS-induced depression model was established in Sprague-Dawley rats. Intrahippocampal injections of QUIN, QUIN antagonist Ro61-8048, non-competitive NMDA receptor antagonist MK-801 and mGluR1 antagonist AIDA were respectively adopted by rat brain stereotaxic coordinates. The behavioral observations were conducted by measurement of weight changes, sucrose preference test, open-field test and tail suspension test. The concentration of glutamic acid (Glu) and the expression of its receptor subunits in hippocampus were detected by HPLC and Western blot, respectively. The QUIN content in hippocampus was determined by enzyme linked immunosorbent assay (ELISA). The result showed that CUMS significantly induced the depressive-like behaviors in rats, increased the contents of QUIN and Glu, and upregulated the expression of NMDA receptor subunits NR2B and mGluR1 in hippocampus. Microinjection of QUIN into hippocampus resulted in animal depressive-like behaviors, and increased the content of Glu and the expression of NR2B and mGluR1 significantly. QUIN antagonist Ro61-8048 effectively restrained the depression-like behaviors induced by CUMS, and decreased the content of Glu and the expression of NR2B and mGluR1 significantly. Intrahippocampal injections of MK-801 and AIDA effectively improved the depression-like behaviors induced by CUMS and decreased the Glu content. The results suggest that CUMS may contribute to the production and release of QUIN in hippocampal microglia. QUIN results in elevation of Glu level via NMDA receptor and mGluR1, and the increase of expression of NR2B and mGluR1 in hippocampus, which leads to depression-like behaviors in the end.

Modulation of hippocampal glutamate and NMDA/AMPA receptor by homocysteine in chronic unpredictable mild stress-induced rat depression / 生理学报

The study was to investigate the role of homocysteine (Hcy) which was released by hippocampal glial cells and its relationship with NMDA receptor and AMPA receptor in depression induced by chronic unpredictable mild stress (CUMS), and explore the mechanism of changes of Glu/Glu receptor in glial cells and neurons. CUMS-induced depression model was established. The body weight of rats was weighed on the 1st, 7th, 14th, and 21st days during the experiment. The behavioral performances were observed by means of sucrose consumption test, open field test and tail suspension test. Intrahippocampal microinjection of Hcy, NMDA receptor antagonist MK-801 and AMPA receptor antagonist NBQX was performed under stereotaxic guide cannula. The concentration of Glu and the expression of its receptors' subunits were detected respectively by high performance liquid chromatography (HPLC) and Western blot. The Hcy content and the levels of phosphorylation of NMDA receptor and AMPA receptor in hippocampus were separately determined by enzyme linked immunosorbent assay (ELISA). The results showed that CUMS significantly induced the depression-like behaviors in rats, and the content of Glu and Hcy, the expression of NMDA receptors' subunits NR1/NR2B and the level of phosphorylation of NMDA receptor (p-NMDAR) in hippocampus increased significantly, while the expression of AMPA receptors' subunits GluR2/3 and the level of phosphorylation of AMPA receptor (p-AMPAR) decreased significantly. Microinjection of Hcy into hippocampus resulted in similar animal depression-like behaviors and increased Glu content compared to the CON/SAL group, the expression of NR1/NR2B/GluR2/3 and the level of p-NMDAR increased significantly, but the level of p-AMPAR reduced observably. Intrahippocampal injections of MK-801 effectively improved the depression-like behaviors induced by CUMS and Hcy, and attenuated the elevation of Glu content induced by Hcy in hippocampus, whereas NBQX could not improve the depression-like behaviors, but also decreased the Glu content induced by Hcy remarkably. These results suggest that CUMS may contribute to the production and release of Hcy via hippocampal astrocytes. Through the increase of expression of NR1/NR2B/GluR2/3 and level of p-NMDAR, and the decrease of level of p-AMPAR, Hcy results in elevation of Glu level, which leads to depression-like behaviors in the end. In a word, the Hcy released by astrocytes plays an important role in stress-induced elevation of Glu content and variation of NMDA/AMPA receptors in hippocampus.

The relationships among raphe magnus nucleus, locus coeruleus and dorsal motor nucleus of vagus in the descending regulation of gastric motility / 中国应用生理学杂志

<p><b>OBJECTIVE</b>To explore the interrelationship among dorsal motor nucleus of the vagus (DMV), locus coeruleus (LC) and raphe magnus nucleus (NRM) in the mechanism of the descending regulation on gastric motility, which may constitute a parasympathetic local circuit, work as a neural center of gastric modulation in brainstem.</p><p><b>METHODS</b>Using nucleus location, electric stimulation and lesion, together with microinjection, and recording the inter-gastric pressure.</p><p><b>RESULTS</b>(1) LC stimulation could inhibit the gastric motility significantly (P < 0.01), DMV lesion weaken this effect, while blocking the a receptor on DMV could reverse the effect. (2) NRM stimulation reduced the amplitude of gastric constriction (P < 0.01), DMV lesion could abolish the effect, but blocking the 5-HT2A receptor on DMV depressed the gastric motility heavily (P < 0.01) like NRM stimulation. While LC lesion could abolish the effect of NRM stimulation, and microinjection of ritanserin into LC could likewise abolish it.</p><p><b>CONCLUSION</b>(1) LC inhibit the gastric motility via a receptor in DMV, and meanwhile may excite it through 5-HT2A receptor in DMV, these two ways work together to keeping the gastric motility amplitude normally. (2) NRM inhibit the gastric motility via 5-HT2A receptor in LC.</p>

Activation of hippocampal D1 dopamine receptor inhibits glutamate-mediated depression induced by chronic unpredictable mild stress in rats / 生理学报

The present study was to investigate the role of dopamine D1 receptors and its relationship with glutamate, N-methyl-D-aspartic acid (NMDA) receptor and α-amino-3-hydroxy-5-methylisoxazole-4-propionic acid (AMPA) receptor in depression induced by chronic unpredictable mild stress (CUMS). CUMS-induced depression model was established in Sprague-Dawley rats, and intrahippocampal microinjections of D1 dopamine receptor agonist SKF38393, non-competitive NMDA receptor antagonist MK-801 and AMPA receptor antagonist NBQX were respectively adopted by rat brain stereotaxic coordinates. The behavioral observations were conducted by measurement of weight changes, sucrose preference test, open-field test and tail suspension test. The concentration of glutamic acid and the expression of its receptors' subunits were detected by HPLC and Western blot, respectively. The results showed that, compared with control group, CUMS rats showed depression-like behavioral changes, higher concentration of glutamic acid, lower expressions of NMDA receptor (NR1) and AMPA receptor (GluR2/3) in hippocampus. Pretreatment with injection of SKF38393 could rescue such depression effect of CUMS, decrease the concentration of glutamic acid, and increase the expressions of NMDA receptor (NR1), AMPA receptor (GluR2/3) in hippocampus. Pretreatment with MK-801 could enhance the antidepressant effect of SKF38393, while NBQX weakened. These results suggest that agonists of D1 dopamine receptor could reduce the concentration of glutamic acid in hippocampus, and its antidepressant effect may be mediated by AMPA receptor partially.

Involvement of hippocampal NMDA receptor and neuropeptide Y in depression induced by chronic unpredictable mild stress / 生理学报

The present study was aimed to investigate the role and relationship between N-methyl-D-aspartic acid (NMDA) receptor and neuropeptide Y (NPY) in depression induced by chronic unpredictable mild stress (CUMS). CUMS-induced depression model was established in Sprague-Dawley rats. Intrahippocampal injections of NMDA, non-competitive NMDA receptor antagonist MK-801 and NPY-Y1 receptor antagonist GR231118 were respectively adopted by rat brain stereotaxic coordinates. The behavioral observations were conducted by sucrose consumption test, open field test and forced swimming test. The expression of NPY in hippocampus was detected by immunohistochemistry. The results showed that compared with the control group, rats receiving CUMS for 21 days or intrahippocampal injection of GR231118 or NMDA showed depression-like behavioral changes, including a reduction in sucrose preference, body weight, locomotor activity, rearing and grooming in open field test, and increased duration of immobility in forced swimming test. Intrahippocampal injection of NMDA decreased the expression of NPY in hippocampal CA3 region and dentate gyrus (DG) region. Intrahippocampal injection of MK-801 improved the depression-like behavioral changes induced by CUMS, and increased the expression of NPY in hippocampal CA3 region and DG region. Co-injection of GR231118 and MK-801showed that GR231118 suppressed the antidepressant effect of MK-801. These data suggest that CUMS might induce depression through excessive release of glutamate (Glu), over-activation of NMDA receptors, and downregulation of NPY. Antidepressant effect of NPY was mainly mediated via NPY-Y1 receptor.

Antidepressant effect of microinjection of neuropeptide Y into the hippocampus is mediated by decreased expression of nitric oxide synthase / 生理学报

Accumulating evidence indicates an important role of hippocampal dendrite atrophy in the development of depression, while neuropeptide Y (NPY) participates in hippocampal dendrite growth. The present study was aimed to investigate the relationship between NPY and nitric oxide synthase (NOS) in chronic unpredictable mild stress (CUMS)-induced depression. CUMS-induced depression model was established in Sprague-Dawley rats. Intrahippocampal microinjections of NPY, NPY-Y1 receptor antagonist GR231118 and non-specific NOS inhibitor N-nitro-L-arginine methyl ester (L-NAME) were respectively adopted by rat brain stereotaxic coordinates. The behavioral observations were conducted by sucrose consumption test, open field test and forced swimming test. The expressions of NPY, neuronal nitric oxide synthase (nNOS) and inducible nitric oxide synthase (iNOS) in hippocampus were detected by immunohistochemistry. The results showed that, compared with the control group, rats receiving CUMS for 21 d or intrahippocampal microinjection of GR231118 showed a significant reduction in body weight and depression-like behavior, which included reductions in sucrose preference, locomotor activity, rearing and grooming in open field test, and increased duration of immobility in forced swimming test. Moreover, the expression of NPY significantly decreased (P<0.01), while the expressions of nNOS and iNOS increased obviously in the hippocampal dentate gyrus (DG) and CA3 regions (P<0.01). Intrahippocampal microinjections of NPY prevented the depression-like behavioral changes induced by CUMS and decreased the expressions of nNOS and iNOS in the hippocampal DG and CA3 regions (P<0.01). Intrahippocampal microinjections of GR231118 reduced behavioral ability of the rats dramatically and significantly increased the expressions of hippocampal nNOS and iNOS (P<0.01). Intrahippocampal microinjections of L-NAME suppressed the depression-like behavioral changes induced by CUMS or intrahippocampal microinjection of GR231118. In conclusion, reduced expression of NPY and increased expression of NOS in hippocampus may make significant contributions to CUMS-induced depression. These results suggest that the antidepressant function of NPY associates with down-regulation of NOS expression in hippocampus, possibly mediated via NPY-Y1 receptor.

The association of hippocampal glutamate with depression and the effects on gastric mobility / 中国应用生理学杂志

<p><b>AIM</b>To explore the relationship between the pathology of depression and glutamate (Glu) in hippocampus, and the effect on gastric mobility.</p><p><b>METHODS</b>Depression model was established by using the chronic unpredicted mild stress (CUMS). And stereotaxic and intra-hippocampal microinjection were also used in this experiment. Rat emotion and behaviors were observed by the change in body weight, sucrose preference-test, open field-test and forced swimming-test. Intragastric pressure and mobility were recorded with the instrument of Powerlab/8sp.</p><p><b>RESULTS</b>Compared with the control, 21-day CUMS significantly reduced the increase in body weight, rat sucrose preference, locomotor activity and rearing in open field test, while it significantly increased duration of immobility time in forced swimming test. Meanwhile, magnitudes of intragastric pressure and mobility were significantly declined after 21 days CUMS. Microinjection of Glu into hippocampus mimics the behaviors which were produced in CUMS. The down-rang of gastric mobility in the group of Glu injection was smaller than CUMS, but was much larger than the control. Intrahippocampal microinjection of MK-801 attenuated depression-like behaviors induced by stress, weakened stress-induced inhibition of intragastric pressure, and augmented the magnitudes of gastric contraction.</p><p><b>CONCLUSION</b>Glu and NMDA receptor in hippocampus are to do much with the etiology of stress- induced depression. They are not only concerned with behavioral changes induced by stress, but also with the variation of gastric activities, nevertheless, differences exist between the effects of behaviors and gastric activities.</p>

Effect and mechnaisim of GLU and GABA in OFC on gastric motility / 中国应用生理学杂志

<p><b>AIM</b>To Investigate the effect of glutamate (Glu) and gamma-aminobutyric acid(GABA) in orbitofrontal cortex (OFC) on regulation of gastric motility.</p><p><b>METHODS</b>Using microinjection in OFC,together with lesion of related nucleus,and recording the intragastric pressure(IGP).</p><p><b>RESULTS</b>(1) Microinjection of Glu in OFC caused a significant reduce of the amplitude of gastric motility, this effect could be reverse by lesion of amygdala, while lesion of LC had no influence on the effect of Glu. (2) microinjection of GABA in OFC could increase the amplitude of gastric motility significantly,and lesion of LC could abolish this effect,while lesion of amygdala could enhance the effect of GABA more.</p><p><b>CONCLUSION</b>Microinjection of Glu in OFC may enhance the normal inhibitory effect of amygdale on gastric motility, and the effect of microinjection of GABA in OFC on gastric motility is closely related with LC.</p>

The effect of sodium 4',7-bihydroxylisoflavone-sulfonate on gastric motility and its mechanism in rat / 中国应用生理学杂志

<p><b>AIM</b>To explore the effect of sodium 4',7-bihydroxylisoflavone-sulfonate (SBIS) on gastric motility in rats and to analyse its mechanisms.</p><p><b>METHODS</b>Using intraperitoneal (ip) injection and intracerebroventriular (icv) microinjection of drugs and recording the frequency and amplitude of contraction of gastric motility.</p><p><b>RESULTS</b>(1) The injection (ip) of different doses of SBIS could decrease the amplitude of gastric motility, but it wasn't a dose-dependent effect. SBIS also had no effect on the frequency of contraction. (2) The ip injection of naloxone reversed the inhibitory effect of SBIS on the amplitude of gastric contraction. (3) The effect of SBIS could be increased by the ip injection of propranolol and be reversed by the ip injection of phentolamine. (4) After the ip injection of atropine, the effect of SBIS on gastric motility had not been changed remarkably. (5) Different doses of SBIS had been microinjected (icy), but only the small dose decreased the amplitude of gastric motility and also the frequency of contraction had not been markedly changed.</p><p><b>CONCLUSION</b>Both the i.p. and icv injection of SBIS can inhibit the gastric motility. Its effect can be achieved at least not only by endogenous opioid peptide and its receptors, but also adrenergic neuron and its alpha-receptors. Adrenergic neuron and its beta-receptors are also involved in the modulating effect of SBIS.</p>

Effects of sodium sulfonate daidzein on stress-induced gastric ulcer and its possible mechanism / 中国应用生理学杂志

<p><b>AIM</b>To investigate the effects of sodium sulfonate daidzein (SSD) on stress-induced gastric ulcer and explore its possible mechanism.</p><p><b>METHODS</b>Using exhausted swimming and counting the number of gastric ulcer to establish the model of stress-induced gastric ulcer. Mouse experience intraperitoneal injection of different doses of SSD and L-NAME, and NDP histochemical method was used to detect the changes of nitric oxide synthase (NOS) positive neurons in stomach.</p><p><b>RESULTS</b>SSD had dose-dependent protective effect on gastric mucosa. L-NAME could prevent stress induced gastric lesion. After combined injection of L-NAME and effective dose of SSD, the protective effect of SSD on gastric mucosa was reinforced. The number of NOS ganglion was constant, and effective dose of SSD had slight effect on NOS-positive neurons in normal mouse while it decreased NOS positive neurons in per area and in per ganglia after stress.</p><p><b>CONCLUSION</b>The increased nitric oxide (NO) leads to gastric ulcer during stress, SSD has protective effect on gastric mucosa and this effect may be mediated by inhibiting NOS and restricting the overproduction of NO during stress.</p>

Effects and mechanism of hypothalamic TRH on cardiac function in rats / 中国应用生理学杂志

<p><b>AIM</b>To investigate the effect of hypothalamic thyrotropin-releasing hormone (TRH) on cardiac function and its mechanism.</p><p><b>METHODS</b>The Sprague-Dawley rats were mounted in a stereotaxic apparatus and a guide cannula placed in the left hypophysiotropic area, through which TRH were microinjected in presence or absence of L-NAME and atropine. The left ventricular systolic pressure (LVSP), heart rate (HR) and the maximum velocity of ascending or descending in intraventricular pressure (+/- dp/dt(max)) were recorded.</p><p><b>RESULTS</b>(1) TRH microinjected into the hypophysiotropic area induced a significant increase of LVSP, HR, dp/dt and-dp/dt(max) (P < 0.05, P < 0.01). (2) L-NAME significant increased LVSP and pretreatment with L-NAME inhibited the positive effects induced by TRH. (3) Atropine increased LVSP and dp/dt(max) (P < 0.05), but it significantly descended heart rate (P < 0.05). Pretreatment with atropine weakened the tachycardiac response induced by TRH.</p><p><b>CONCLUSION</b>(1) Hypothalamic TRH can produce positive inotropic and chronotropic response to myocardium. (2) Hypothalamic endogenous NO can descend LVSP, but has no effects on HR, dp/dt(max), and-dp/dt(max). The effect of TRH is through nitric oxide-dependent pathway. (3) Hypothalamic endogenous cholinergic transmitter can produce negative chronotropic and positive inotropic response to myocardium. Hypothalamic TRH mediates cardiac function maybe partly through cholinergic M receptor.</p>

Study of mechanism and the effect of intracerebroventricular microinjection of serotonin on gastric motility in rabbit / 中国应用生理学杂志

<p><b>AIM</b>To explore the effect of central serotonin (5-hydroxytryptamine, 5-HT) on gastric motility in rabbit and to analysis its mechanism.</p><p><b>METHODS</b>Intracerebroventricular (icv) microinjection of drugs were used. The frequency and the amplitude of contractions of gastric motility were recorded.</p><p><b>RESULTS</b>(1) Injection (icv) of 25 microg 5-HT increased the amplitude of contractions and decreased the frequency of gastric motility. (2) The effects of 5-HT were inhibited by injection (icv) of atropine, but intravenous(iv) injection of atropine could only block the increase effect of 5-HT on intragastric pressure. After injection (icv or iv) of phentolamine or propranolol, the effects of 5-HT on gastric motility were not changed markedly. (3) Microinjection (icv) of naloxone or diphenhydramine inhibited the inhibitory effect of 5-HT on the frequency of gastric contractions, and the diphenhydramine reversed the increase effect of 5-HT on intragastric pressure. (4) Vagotomy abolished the effects of 5-HT completely.</p><p><b>CONCLUSION</b>There may be different nerve mechanisms in regulation of central 5-HT on the frequency and amplitude of contractions of gastric motility. The increase effect of 5-HT on intragastric pressure is medicated by the cholinergic system in brain, and histamine may be one of the important element on the effect of 5-HT. The cholinergic fibers in vagus nerve transmit the effect. The inhibitory effect of 5-HT on the frequency of contractions is also medicated by activating the cholinergic system in brain, enkephalin and histamine are also involved, and it is transmitted via noncholinergic and nonadrenergic fibers in vagus nerve.</p>