Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UMLS:C0040822 (tremor)
 18,428 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Acute restraint and shaking stress each induced the mRNA for the immediate early gene (IEG), c-fos, within 1 h in locus coeruleus (LC), midbrain raphe nuclei and central gray. Both acute restraint stress and acute shaking stress activated c-fos and zif/268 mRNA in paraventricular nuclei within 1 h. Midbrain A9 and A10 dopaminergic neurons did not show any c-fos or zif/268 mRNA induction by either acute stressor. Repeated restraint stress (14d, 1h/d) produced habituation to acute restraint stress, but not to acute shaking stress, in PVN, raphe and central gray. In LC, repeated restraint stress caused some habituation to both acute stressors.
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PMID:Induction and habituation of c-fos and zif/268 by acute and repeated stressors. 791 89

In this study, the animal model of hypertonic saline (HS) infusion protocol was developed and utilized to test the hypothesis that HS causes peripheral release of glutamate, and that blockade of peripheral NMDA receptors significantly reduces HS-induced nocifensive behavior and central neuronal activation. Nocifensive behavior and c-fos immunoreactivity, as a marker of central neuronal activation, were assessed from the animals that received intramuscular HS infusion with and without the NMDA receptor antagonist, MK-801. HS infusion (20 microl/min for 10 min) in the rat masseter produced prolonged nocifensive hindpaw shaking responses that peaked in the first minute and gradually diminished over the infusion period. The HS induced nocifensive behavior was dose-dependently attenuated by MK-801 pretreatments (0.3 mg/kg and 0.1 mg/kg), but not by vehicle pretreatment (isotonic saline; ISO), in the masseter muscle. HS infusion produced a significant number of Fos positive neurons in the ispsilateral subnucleus caudalis (Vc). Subsequent immunohistochemical studies showed that peripheral MK-801 pretreatment effectively reduced the HS induced neuronal activation in the Vc. These results provide compelling evidence that HS-induced muscle nociception is mediated, in part, by peripheral release of glutamate, and that blockade of peripheral glutamate receptors may provide effective means of preventing central neuronal activation.
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PMID:Hypertonic saline-induced muscle nociception and c-fos activation are partially mediated by peripheral NMDA receptors. 1687 52

In this study, involvement of peripheral AMPA receptors in mediating craniofacial muscle pain was investigated. AMPA receptor subunits, GluR1 and GluR2, were predominantly expressed in small to medium size neurons but more GluR2 positive labeling were encountered in trigeminal ganglia (TG) of male Sprague Dawley rats. A greater prevalence of GluR2 is reflected by the significantly higher percentage of GluR2 than GluR1 positive masseter afferents. Nocifensive behavior and c-fos immunoreactivity were assessed from the same animals that received intramuscular mustard oil (MO) with or without NBQX, a potent AMPA/KA receptor antagonist. Masseteric MO produced nocifensive hindpaw shaking responses that peaked in the first 30s and gradually diminished over a few minutes. There was a significant difference in both peak and overall MO-induced nocifensive responses between NBQX and vehicle pre-treated rats. Subsequent Fos studies also showed that peripheral NBQX pre-treatment effectively reduced the MO-induced neuronal activation in the subnucleus caudalis of the trigeminal nerve (Vc). These combined results provide compelling evidence that acute muscle nociception is mediated, in part, by peripherally located AMPA/KA receptors, and that blockade of multiple peripheral glutamate receptor subtypes may provide a more effective means of reducing muscular pain and central neuronal activation.
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PMID:Peripheral AMPA receptors contribute to muscle nociception and c-fos activation. 1865 11

Repeated exposure to opiates leads to cellular and molecular changes and behavioral alterations reflecting a state of dependence. In noradrenergic neurons, cyclic AMP (cAMP)-dependent pathways are activated during opiate withdrawal, but their contribution to the activity of locus coeruleus noradrenergic neurons and behavioral manifestations remains controversial. Here, we test whether the cAMP-dependent transcription factors cAMP responsive element binding protein (CREB) and cAMP-responsive element modulator (CREM) in noradrenergic neurons control the cellular markers and the physical signs of morphine withdrawal in mice. Using the Cre/loxP system we ablated the Creb1 gene in noradrenergic neurons. To avoid adaptive effects because of compensatory up-regulation of CREM, we crossed the conditional Creb1 mutant mice with a Crem-/- line. We found that the enhanced expression of tyrosine hydroxylase normally observed during withdrawal was attenuated in CREB/CREM mutants. Moreover, the withdrawal-associated cellular hyperactivity and c-fos expression was blunted. In contrast, naloxone-precipitated withdrawal signs, such as jumping, paw tremor, tremor and mastication were preserved. We conclude by a specific genetic approach that the withdrawal-associated hyperexcitability of noradrenergic neurons depends on CREB/CREM activity in these neurons, but does not mediate several behavioral signs of morphine withdrawal.
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PMID:Effects of the cell type-specific ablation of the cAMP-responsive transcription factor in noradrenergic neurons on locus coeruleus firing and withdrawal behavior after chronic exposure to morphine. 2036 54

Expression of the immediate early gene, c-fos, was examined in a large animal model of non-accidental head injury ("shaken baby syndrome"). Lambs were used because they have a relatively large gyrencephalic brain and weak neck muscles resembling a human infant. Neonatal lambs were manually shaken in a manner similar to that believed to occur with most abused human infants, but there was no head impact. The most striking c-fos expression was in meningothelial cells of the cranial cervical spinal cord and, to a lesser degree, in hemispheric, cerebellar, and brainstem meninges. Vascular endothelial cells also frequently showed c-fos immunopositivity in the meninges and hemispheric white matter. It was hypothesised that this c-fos immunoreactivity was due to mechanical stress induced by shaking, with differential movement of different craniospinal components.
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PMID:Pattern of cerebrospinal immediate early gene c-fos expression in an ovine model of non-accidental head injury. 2403 22

Depression is a common comorbid condition in Parkinson's disease (PD). Patients with depression have a two-fold increased risk to develop PD. Further, depression symptoms often precede motor symptoms in PD and are frequent at all stages of the disease. However, the influence of a depressive state on the responses to antiparkinson treatments is largely unknown. In this study, the genetically inbred depression-like flinders sensitive line (FSL) rats and control flinders resistant line (FRL) rats were studied in models of experimental parkinsonism. FSL rats showed a potentiated tremorgenic response to tacrine, a cholinesterase inhibitor used experimentally to induce 6 Hz resting tremor reminiscent of parkinsonian tremor. We also studied rats lesioned with 6-OHDA to induce hemiparkinsonism. No baseline differences in dopaminergic response to acute apomorphine or L-DOPA was found. However, following chronic treatment with L-DOPA, FRL rats developed sensitization of turning and abnormal involuntary movements (AIMs); these effects were counteracted by the anti-dyskinetic 5-HT1 A agonist/D2 partial agonist sarizotan. In contrast, FSL rats did not develop sensitization of turning and only minor AIMs in response to L-DOPA treatment. The roles of several non-dopamine systems underlying this discrepancy were studied. Unexpectedly, no differences of opioid neuropeptides or serotonin markers were found between FRL and FSL rats. The marked behavioral difference between the FRL and FSL rats was paralleled with the striatal expression of the established marker, c-fos, but also the GABAergic transporter (vGAT), and a hitherto unknown marker, tamalin, that is known to regulate mGluR5 receptor function and postsynaptic organization. This study demonstrates that behavioral and transcriptional responses of non-dopaminergic systems to experimental parkinsonism and L-DOPA are modified in a genetic rat model of depression.
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PMID:Non-dopaminergic Alterations in Depression-Like FSL Rats in Experimental Parkinsonism and L-DOPA Responses. 3226 3

Lithium, commonly used to treat bipolar disorder, potentiates the ability of the muscarinic agonist pilocarpine to induce seizures in rodents. As this potentiation by lithium is reversed by the administration of myo-inositol, the potentiation may be mediated by inhibition of inositol monophosphatase (IMPase), a known target of lithium. Recently, we demonstrated that ebselen is a 'lithium mimetic' in regard to behaviours in both mice and man. Ebselen inhibits IMPase in vitro and lowers myo-inositol in vivo in the brains of mice and men, making ebselen the only known inhibitor of IMPase, other than lithium, that penetrates the blood-brain barrier. Our objective was to determine the effects of ebselen on sensitization to pilocarpine-induced seizures and neural activity. We administered ebselen at different doses and time intervals to mice, followed by injection of a sub-seizure dose of pilocarpine. We assessed seizure and neural activity by a subjective seizure rating scale, by monitoring tremors, and by induction of the immediate early gene c-fos. In contrast to lithium, ebselen did not potentiate the ability of pilocarpine to induce seizures. Unexpectedly, ebselen inhibited pilocarpine-induced tremor as well as pilocarpine-induced increases in c-fos mRNA levels. Both lithium and ebselen inhibit a common target, IMPase, but only lithium potentiates pilocarpine-induced seizures, consistent with their polypharmacology at diverse molecular targets. We conclude that ebselen does not potentiate pilocarpine-induced seizures and instead, reduces pilocarpine-mediated neural activation. This lack of potentiation of muscarinic sensitization may be one reason for the lack of side-effects observed with ebselen treatment clinically.
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PMID:Effects of the putative lithium mimetic ebselen on pilocarpine-induced neural activity. 3268 20