Disease relevance of Arc

• The mRNA expression patterns of SVCT2 and the glutamate-activated immediate early gene Arc were investigated at 2 and 22 h after ischemia [1].
• Effect of 5-HT depletion by MDMA on hyperthermia and Arc mRNA induction in rat brain [2].
• The present results suggest that Arc may play an important role in the neuronal plasticity through NMDA activation following focal cerebral ischemia [3].
• The interaction of Arc with CaM kinase II was demonstrated using GST-Arc fusion protein, and confirmed in neuroblastoma cells by immunoprecipitation [4].Psychiatry related information on Arc

• The present data show that Arc has a neuroanatomically restricted pattern of induction in the brain after emotional stress [5].
• Exposure to lead elevates induction of zif268 and Arc mRNA in rats after electroconvulsive shock: the involvement of protein kinase C [6].
• The immediate-early gene Arc is transcribed in neurons that are part of stable neural networks activated during spatial exploratory behaviors [7].
• The results also show that the increase in rapid eye movement sleep P-wave density during the post-training 3-h recording session is positively correlated with the increased levels of phosphorylated CREB, BDNF and Arc in the dorsal hippocampus [8].
• Taken together, the foregoing suggests that decreasing NMDA receptor activation during early stages of chronic neuroinflammation should reduce a) microglia activation, b) overexpression of Arc, and c) spatial memory deficits [9].

High impact information on Arc

• Environment-specific expression of the immediate-early gene Arc in hippocampal neuronal ensembles [10].
• These results demonstrate that NMDA receptor activation is required for the targeting of Arc mRNA to active synapses [11].
• AMPA receptor antagonists (CNQX) blocked targeting of Arc mRNA in a small region, and mGluR antagonists (MCPG) did not affect localization [11].
• Newly synthesized Arc protein also accumulates in the portion of the dendrite that had been synaptically activated [12].
• Here, we report that high frequency activation of the perforant path projections to the dentate gyrus causes newly synthesized mRNA for the immediate-early gene (IEG) Arc to localize selectively in activated dendritic segments [12].
• The consolidation of long-term potentiation (LTP) in the dentate gyrus requires a period of sustained Arc protein synthesis [13]
• Arc protein synthesis during LTP consolidation is required for cofilin phosphorylation and enhanced formation of filamentous actin within the termination zone of the medial perforant path input to the dentate gyrus [13].
• Sustained synthesis of Arc during LTP consolidation is mediated by sustained BDNF-TrkB signaling to MAP kinase interacting kinase (MNK1). MNK controls translation in mechanistically distinct early and late stages [14][15]

Biological context of Arc

• Stress-induced activation of the immediate early gene Arc (activity-regulated cytoskeleton-associated protein) is restricted to telencephalic areas in the rat brain: relationship to c-fos mRNA [5].
• Antidepressant drug treatment induces Arc gene expression in the rat brain [16].
• Up-regulation of Arc expression may be part of the process by which antidepressant drugs achieve long-term changes in synaptic function in the brain [16].
• Electron microscopic immunocytochemical methods were used to determine the localization, subcellular distribution and expression of activity-regulated cytoskeletal protein (Arc/Arg3.1) in dentate gyrus after unilateral induction of long-term potentiation (LTP) in the perforant pathway of anaesthetized rats [17].
• The purpose of the present study is to examine the fidelity of Arc mRNA translation and the temporal dynamics of behaviorally induced Arc protein expression after rats explore a novel environment [7].

Anatomical context of Arc

• Furthermore, Arc interacted with newly polymerized microtubules and MAP2, leading to blocking of the epitope of MAP2 [18].
• Our observations suggest that Arc may play a role in activity-dependent plasticity of dendrites [19].
• For instance, activation of Arc but not c-fos was observed in the nucleus accumbens after immobilization and in the hippocampus after novel environment [5].
• Constitutive Arc expression was observed in some areas such as cortex, striatum, hippocampus, reticular thalamic nucleus and cerebellar cortex [5].
• In contrast, paroxetine (5 mg/kg s.c.) increased Arc mRNA after pre-treatment with WAY 100635 (0.3 mg/kg s.c.). This increase was apparent in cortical regions (frontal, parietal and cingulate) and caudate nucleus but was absent in hippocampus (CA1) [20].

Associations of Arc with chemical compounds

• An increase in central postsynaptic 5-hydroxytryptamine (5-HT) function activates expression of activity-related cytoskeletal protein (Arc) [20].
• In situ hybridization studies found that neither paroxetine (5 mg/kg s.c.) nor WAY 1000635 (0.3 mg/kg s.c.) altered Arc mRNA abundance in any region examined [20].
• We investigated the patterns of Arc expression evoked in the rat striatum by acute exposures to two psychomotor stimulants, cocaine and amphetamine [21].
• In conclusion, paroxetine and WAY 100635 injected in combination (but not alone) caused a region-specific, 5-HT-mediated increase in Arc expression [20].
• The increase in Arc expression induced by paroxetine/WAY 100635 was abolished by the 5-HT synthesis inhibitor, p-chlorophenylalanine (300 mg/kg i.p., daily for two days) [20].

Regulatory relationships of Arc

• Sated rats were assessed for food consumption in the presence of a cue that was paired previously with food (CS+), or in the presence of another cue that was never paired with food (CS-), in two consecutive tests temporally arranged for activation of the effector IEGs Arc (activity-regulated cytoskeletal protein) and Homer 1a [22].
• Local infusion of the transcription inhibitor actinomycin D (ACD) 1 hr before or immediately before BDNF infusion inhibited BDNF-LTP and upregulation of Arc protein expression [23].
• Glutamate receptor activation is involved in 5-HT2 agonist-induced Arc gene expression in the rat cortex [24].
• We examined the function of Arc by introducing Arc cDNA into neuroblastoma cells expressing CaM kinase II [4].

Other interactions of Arc

• The contrasting patterns of Arc expression evoked by cocaine and amphetamine parallel those of c-Fos, JunB, FRA, and NGFI-A expression induced by these two psychomotor stimulants [21].
• Zif268, Arc and Homer can be modulated in CA1 pyramidal cells approximately twofold after electroshock-induced maximal seizure, which demonstrates potential responsiveness to electrical stimuli [25].
• Single-cell transcriptional analysis of Arc after whole-cell patch-clamp recordings indicated that increased gene expression correlated with enhancement of synaptic transmission by BDNF [26].
• Use of Arc expression as a molecular marker of increased postsynaptic 5-HT function after SSRI/5-HT1A receptor antagonist co-administration [20].
• Mating behavior induces differential Arc expression in the main and accessory olfactory bulbs of adult rats [27].

Analytical, diagnostic and therapeutic context of Arc

• Here, we compared the induction of both c-fos and Arc mRNAs in the brain of rats exposed to one of three different stressful situations: novel environment, forced swimming and immobilization [5].
• We used immunocytochemical electron microscopy to determine whether the subcellular localization of Arc in developing dendrites corresponds to the peak period of synaptogenesis in the postnatal rat caudate-putamen nucleus (CPN) [28].
• Here in situ hybridisation and immunohistochemistry were used to examine whether Arc expression in rat brain is altered by antidepressant drug treatment [16].
• We used fluorescent in-situ hybridization and confocal microscopy to monitor the subcellular distribution of the immediate-early gene Arc. Arc RNA appeared in discrete intranuclear foci within minutes of neuronal activation and subsequently disappeared from the nucleus and accumulated in the cytoplasm by 30 minutes [10].
• Effects of stress and adrenalectomy on activity-regulated cytoskeleton protein (Arc) gene expression [29].

References