UMLS:C0011570 - FACTA Search

Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0011570 (depression)
172,036 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The effects of the specific p42/44 mitogen-activated protein (MAP) kinase cascade inhibitor, PD98059, were investigated on three types of long-term potentiation (LTP) in the medial perforant path of the rat dentate gyrus in vitro: LTP induced by 1) high-frequency stimulation (HFS-LTP), 2) application for 10 min of the K+ channel blocker, tetraethylammonium chloride (TEA-LTP), and 3) application of the metabotropic glutamate receptor (mGluR) agonist (S)-dihydrophenylglycine (S-DHPG) for 2 min (DHPG-LTP). Bath perfusion of PD98059 (50 microM) for 1 h inhibited HFS-LTP (111 +/- 5%, mean +/- SE, at 90 min posttetanus in test slices compared with 144 +/- 5% in control slices; n = 6-7). Concentrations of 10 and 20 microM PD98059 had no effect on HFS-LTP (n = 6). PD98059 (50 microM) had no effect on the isolated N-methyl--aspartate excitatory postsynaptic potential (NMDA-EPSP) or on the maintenance phase of HFS-LTP. PD98059 (50 microM) did not affect paired-pulse depression (PPD; interstimulus intervals of 10 and 100 ms) of synaptic transmission as is typically observed in the medial perforant path of the dentate gyrus. Bath application of (S)-DHPG (40 microM) for 2 min gave rise to a potentiation of the EPSPs slope (148 +/- 4% at 1 h post-DHPG wash out; n = 5). Pretreatment of slices with PD98059 (50 microM) inhibited the DHPG-LTP (98 +/- 3% at 1 h post-DHPG wash out; n = 5). The TEA-LTP (125 +/- 4% at 1 h post-TEA wash out; n = 6) was found to be both -2-amino-5-phosphonopentanoic acid (-AP5; 100 microM) and nifedipine (20 microM) independent. However, the T type voltage-dependent calcium-channel blocker, NiCl2 (50 microM), completely inhibited the observed potentiation. The mGluR receptor antagonist alpha-methyl-4-carboxy-phenyl glycine (MCPG; 100 microM) and PD98059 (50 microM) caused a complete block of the TEA-LTP. These data show for the first time an involvement of the p42/44 MAP kinase in the induction and expression of both an NMDA-dependent and two forms of NMDA-independent LTP in the dentate gyrus.
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PMID:P42/44 MAP kinase inhibitor PD98059 attenuates multiple forms of synaptic plasticity in rat dentate gyrus in vitro. 991 71

1. The role of phosphorylation in synaptic transmission was investigated at a large glutamatergic terminal, the endbulb of Held, on bushy cells in the rat anteroventral cochlear nucleus (AVCN). 2. Whole-cell recordings of excitatory postsynaptic currents (EPSCs) were used to examine the effects of kinase inhibitors and activators on low-frequency (baseline) evoked release, spontaneous release, paired-pulse facilitation (PPF) or depression (PPD), repetitive stimuli and recovery from depression. 3. Application of the kinase inhibitor H7 (100 microM) reduced low-frequency evoked EPSC amplitude (by 15 %) and simultaneously increased PPF (or reduced PPD), with no significant change in other aspects of transmission. H7 did not affect the amplitude or frequency of spontaneous miniature EPSCs. 4. Phorbol esters increased EPSC amplitude (by 50 %) with a concomitant decrease in PPF (or increase in PPD), and reduced the final EPSC amplitude during repetitive stimuli. The effect of phorbol esters was due exclusively to protein kinase C (PKC) activation, as the specific PKC inhibitor bis-indolylmaleimide (Bis) completely blocked the potentiating effect of phorbol esters on EPSC amplitude. 5. Significantly, phorbol esters did not increase the evoked EPSC amplitude at connections in which release was maximized using high extracellular calcium concentrations (4-6 mM). 6. Phorbol esters increased the frequency of spontaneous miniature EPSCs in physiological calcium (by 275 %), and in high extracellular calcium (by 210 %) when phorbol esters did not increase the evoked EPSC amplitude. 7. Our results are most consistent with the actions of H7 to decrease low-frequency release probability and phorbol esters to increase low-frequency release probability at the endbulb-bushy cell synaptic connection in the AVCN. The effects of H7 and phorbol esters on paired-pulse responses and tetanic depression appear to be largely consequential to these changes in low-frequency release probability.
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PMID:Phosphorylation regulates spontaneous and evoked transmitter release at a giant terminal in the rat auditory brainstem. 1089 23

We have previously provided functional evidence that glycine and GABA are contained in the same synaptic vesicles and coreleased at the same synapses in lamina I of the rat spinal dorsal horn. However, whereas both glycine receptors (GlyRs) and GABA(A) receptors (GABA(A)Rs) are expressed on the postsynaptic target, under certain conditions inhibitory events appeared to be mediated by GlyRs only. We therefore wanted to test whether GABA(B) receptors could be activated in conditions where GABA released was insufficient to activate GABA(A)Rs. Focal stimulation in the vicinity of visually identified lamina I neurons elicited monosynaptic IPSCs in the presence of ionotropic glutamate receptor antagonists. Pairs of stimuli were given at different interstimulus intervals (ISI), ranging from 25 ms to 1 s to study the depression of the second of evoked IPSCs (paired pulse depression; PPD). Maximal PPD of IPSCs was 60 +/- 14% (SE) (of the conditioning pulse amplitude), at ISI between 150 and 200 ms. PPD was observed with IPSCs evoked at stimulus intensities where they had no GABA(A)R component. PPD of small evoked IPSCs was not affected by the GABA(A)R antagonist bicuculline but significantly attenuated by 10-30 microM CGP52432, a specific GABA(B) receptor antagonist. These data indicate that, under conditions where GABA released is insufficient to affect postsynaptic GABA(A)Rs at lamina I inhibitory synapses, significant activation of presynaptic GABA(B) receptors can occur.
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PMID:GABA(B) receptors are the first target of released GABA at lamina I inhibitory synapses in the adult rat spinal cord. 1093 23

Paired recordings between CA3 interconnected pyramidal neurons were used to study the properties of short-term depression occurring in these synapses under different frequencies of presynaptic firing (n = 22). In stationary conditions (0.05-0.067 Hz) pairs of presynaptic action potentials (50 ms apart) evoked EPSCs whose amplitude fluctuated from trial to trial with occasional response failures. In 15/20 cells, paired-pulse ratio (PPR) was characterized by facilitation (PPF) while in the remaining five by depression (PPD). Increasing stimulation frequency from 0.05-0.067 Hz to 0.1-1 Hz induced low frequency depression (LFD) of EPSC amplitude with a gradual increase in the failure rate. Overall, 9/12 cells at 1 Hz became almost "silent". In six cells in which the firing rate was sequentially shifted from 0.05 to 0.1 and 1 Hz, changes in synaptic efficacy were so strong that PPR shifted from PPF to PPD. The time course of depression of EPSC1 could be fitted with single exponentials with time constants of 98 and 36 s at 0.1 and 1 Hz, respectively. In line with the inversion of PPR at 1 Hz, the time course of depression of EPSC2 was faster than EPSC1 (7 s). Recovery from depression could be obtained by lowering the frequency of stimulation to 0.025 Hz. These results could be explained by a model that takes into account two distinct release processes, one dependent on the residual calcium and the other on the size of the readily releasable pool of vesicles.
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PMID:Frequency-dependent shift from paired-pulse facilitation to paired-pulse depression at unitary CA3-CA3 synapses in the rat hippocampus. 1238 19

This study examined the cellular actions of the anti-migraine drug sumatriptan, on neurons in the substantia gelatinosa of the spinal trigeminal nucleus pars caudalis. Sumatriptan inhibited the miniature EPSC (mEPSC) rate in a dose dependent fashion, with an EC(50) of 250 nM. Sumatriptan (3 microM) inhibited the mEPSC rate by 36%, without altering the mEPSC amplitude. This effect was partially reversed by the 5HT(1D) specific antagonist BRL15572 (10 microM). In contrast, the 5HT(1B) agonist CP93129 (10 microm) did not alter the mEPSC rate. Furthermore, sumatriptan (3 microM) decreased the amplitude of electrically evoked EPSCs (eEPSC) by 40%. After incubating the slices in ketanserin (an antagonist which shows selectivity for 5HT(1D) over 5HT(1B) receptors) sumatriptan had little effect on eEPSC amplitude. In control conditions paired stimuli resulted in paired pulse depression (PPD; the ratio eEPSC(2)/eEPSC(1)=0.7+/-0.01), whilst in the presence of sumatriptan the PPD was blocked (ratio eEPSC(2)/eEPSC(1)=0.9+/-0.1). Sumatriptan produced no post-synaptic membrane current and had no significant effect on membrane conductance over a range of membrane potentials (-60 to -130 mV). RT-PCR experiments revealed the presence of mRNA for both 5HT(1D) and 5HT(1B) receptor subtypes in the trigeminal ganglia and subnucleus caudalis. These data suggest that sumatriptan acts pre-synaptically on trigeminal primary afferent central terminals to reduce the probability of release of glutamate, and that this action is mediated through 5HT(1D) receptors.
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PMID:Effects of sumatriptan on rat medullary dorsal horn neurons. 1532 6

The extrinsic innervation of the pancreas converges on a plexus of intrinsic pancreatic ganglia whose cholinergic neurons innervate acini, ducts, islets and blood vessels. Therefore, understanding ganglionic transmission is essential for understanding neural control of pancreatic secretion. Intracellular recordings of nicotinic fast excitatory postsynaptic potentials (fEPSPs) and action potentials (APs) were used to characterize and compare transmission in ganglia from the head/neck and body regions of the rabbit pancreas. Paired-pulse facilitation (PPF) or depression (PPD) of fEPSPs was observed in ganglia from both regions with PPF peaking and disappearing at shorter inter-stimulus intervals than PPD. PPF was most frequent in the head/neck (60%) and PPD (50%) in the body. Repetitive stimulation (10 Hz/5 s) evoked multiple forms of mid- and post-train plasticity. Facilitation during the first 1-2 s of train stimulation was reduced or reversed with continued stimulation due to development of synaptic depression and mid-train depression was of greater magnitude in the head/neck region. A brief (approximately 10 s) post-train augmentation was followed by a 1-2 min post-train depression that appeared to result from inhibition of ACh release. Regional differences in the frequency, magnitude, or duration of all forms of synaptic plasticity suggested regional differences in the extrinsic innervation patterns and possibly the function of pancreatic ganglia. In conclusion, rabbit pancreatic ganglia exhibit multiple forms of short-term synaptic plasticity that markedly alter the probability of postsynaptic firing, consistent with these ganglia being critical sites of synaptic integration and autonomic regulation of pancreatic secretion.
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PMID:Short-term synaptic plasticity in rabbit pancreatic ganglia. 1589 6

While it is known that ethanol augments GABA-A receptor mediated inhibition in the central nervous system (CNS), demonstrating direct effects of ethanol on GABA transmission has been difficult in brain slices, suggesting that these preparations may lack factors that are required for ethanol's actions. Recent studies indicate that the GABA-enhancing neurosteroid 3alpha-hydroxy-5alpha-pregnan-20-one (3alpha5alphaP) mediates at least some effects of ethanol in the CNS. In the CA1 region of rat hippocampal slices, we found that 60mM ethanol failed to alter paired pulse depression (PDD) of population spikes (PSs) when paired stimuli were delivered to the Schaffer collateral pathway at an interval of 21ms. Following 2-h preincubation of slices with 100nM 3alpha5alphaP, however, ethanol augmented PS PPD. This effect was not observed in the presence of picrotoxin, a GABA-A receptor antagonist, or ADVASEP-7, a beta-cyclodextrin that binds 3alpha5alphaP. These results indicate that 3alpha5alphaP modulates the inhibitory effects of ethanol on hippocampal excitability via GABA-A receptors.
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PMID:Effects of neurosteroid 3alpha-hydroxy-5alpha-pregnan-20-one on ethanol-mediated paired-pulse depression of population spikes in the CA1 region of rat hippocampal slices. 1637 87

It is important to consider the potential contribution of seasonality to postpartum depression (PPD; Hiltunen et al, 2004). A possible link between seasonality and PPD may have implications for not only choice of treatment, but also in considering pregnancy planning. The objectives of this pilot study were to examine whether women with seasonal mood changes demonstrated greater incidence of PPD, and to determine if seasonality scores were predictive of PPD. The Seasonal Pattern Assessment Questionnaire (SPAQ; Rosenthal et al, 1987) was used to assess seasonality of mood. A logistic regression analysis was conducted to determine the association between clinical factors, SAD diagnosis, SPAQ global seasonality score (GSS) and season of SPAQ administration and PPD. In our sample, twice as many women in the PPD group were found to have SAD compared to the control group. The PPD group also had a higher group GSS mean (10.44) than did the control group (8.84). However, logistic regression analysis showed that higher seasonality scores in women with PPD were not necessarily predictive of PPD. While more women in the PPD group reported increased seasonal weight fluctuation and less sleep in the spring and summer, these items alone did not predict depression after childbirth.
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PMID:Seasonality of symptoms in women with postpartum depression. 1716 99

Paired-pulse facilitation (PPF) and depression (PPD) are forms of short-term plasticity that are generally thought to reflect changes in transmitter release probability. However, desensitization of postsynaptic AMPA receptors (AMPARs) significantly contributes to PPD at many glutamatergic synapses. To clarify the involvement of AMPAR desensitization in synaptic PPD, we compared PPD with AMPAR desensitization, induced by paired-pulse glutamate application in patches excised from postsynaptic cells at the calyx of Held synapse of developing rats. We found that AMPAR desensitization contributed significantly to PPD before the onset of hearing (P10-12), but that its contribution became negligible after hearing onset. During postnatal development (P7-21) the recovery of AMPARs from desensitization became faster. Concomitantly, glutamate sensitivity of AMPAR desensitization declined. Single-cell reverse transcription-polymerase chain reaction (RT-PCR) analysis indicated a developmental decline of GluR1 expression that correlated with speeding of the recovery of AMPARs from desensitization. Transmitter release probability declined during the second postnatal week (P7-14). Manipulation of the extracellular Ca2+/Mg2+ ratio, to match release probability at P7-8 and P13-15 synapses, revealed that the release probability is also an important factor determining the involvement of AMPAR desensitization in PPD. We conclude that the extent of involvement of AMPAR desensitization in short-term synaptic depression is determined by both pre- and postsynaptic mechanisms.
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PMID:Involvement of AMPA receptor desensitization in short-term synaptic depression at the calyx of Held in developing rats. 1833 95

Many studies have demonstrated that GABAergic inhibition within the basolateral amygdala (BLA) plays an integral role in the regulation of anxiety, an important behavioral component in the etiology of alcoholism. Although ethanol has recently been shown to enhance BLA GABAergic inhibition via two distinct populations of inhibitory cells, local and lateral paracapsular (lpcs) interneurons, little is known about the mechanisms underlying ethanol potentiation of these two inhibitory pathways. Ethanol is known to enhance GABAergic inhibition in many brain regions via a complex array of pre- and postsynaptic mechanisms. In addition, ethanol's presynaptic effects are often subject to GABA(B) autoreceptor (GABA(B)-R) modulation. Therefore, in this study, we characterized GABA(B)-R function and modulation of ethanol actions at local and lpcs GABAergic synapses. At local synapses, we found significant paired-pulse depression (PPD, 250 ms inter-pulse interval) which was abated by SCH-50911 (GABA(B)-R antagonist). No significant PPD was detected at lpcs synapses, but SCH-50911 significantly potentiated lpcs-evoked IPSCs. Baclofen (GABA(B)-R agonist) had similar depressant effects on local- and lpcs-evoked IPSCs, however baclofen pretreatment only reduced ethanol potentiation at local synapses. Ethanol also significantly enhanced the frequency of spontaneous and miniature IPSCs, and these effects were also sensitive to GABA(B)-R modulators. Collectively, these data suggest that stimulus-independent inhibitory responses recorded from BLA principal neurons primarily reflect the activity of local GABAergic interneurons and provide additional evidence that ethanol potentiates local BLA inhibitory synapses primarily via a presynaptic enhancement of GABA release that is tightly regulated by GABA(B)-Rs. In contrast, ethanol potentiation of lpcs GABAergic synapses is not sensitive to GABA(B)-R activation and does not appear to involve increased presynaptic GABA release.
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PMID:Differential effects of GABAB autoreceptor activation on ethanol potentiation of local and lateral paracapsular GABAergic synapses in the rat basolateral amygdala. 1937 78

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