Glucocorticoid receptor and protein/RNA synthesis-dependent mechanisms underlie the control of synaptic plasticity by stress

Learning and memory are exquisitely sensitive to behavioral stress, but the underlying mechanisms are still poorly understood. Because activity-dependent persistent changes in synaptic strength are believed to mediate memory processes in brain areas such as the hippocampus we have examined the means by which stress affects synaptic plasticity in the CA1 region of the hippocampus of anesthetized rats, Inescapable behavioral stress (placement on an elevated platform for 30 min) switched the direction of plasticity, favoring low frequency stimulation-induced decreases in synaptic transmission (long-term depression, LTD), and opposing the induction of long-term potentiation by high frequency stimulation, We have discovered that glucocorticoid receptor activation mediates these effects of stress on LTD and longterm potentiation in a protein synthesis-dependent manner because they were prevented by the glucocorticoid receptor antagonist RU 38486 and the protein synthesis inhibitor emetine. Consistent with this, the ability of exogenously applied corticosterone in non-stressed rats to mimic the effects of stress on synaptic plasticity was also blocked by these agents, The enablement of low frequency stimulation-induced LTD by both stress and exogenous corticosterone was also blocked by the transcription inhibitor actinomycin D, Thus, naturally occurring synaptic plasticity is liable to be reversed in stressful situations via glucocorticoid receptor activation and mechanisms dependent on the synthesis of new protein and RNA, This indicates that the modulation of hippocampus-mediated learning by acute inescapable stress requires glucocorticoid receptor-dependent initiation of transcription and translation.

Both stress experience and age determine the impairment or enhancement effect of stress on spatial memory retrieval

It has been documented that stress or glucocorticoids have conflicting effects on memory under different conditions. However, it is not fully understood why stress can either impair or enhance memory. Here, we have examined the performance of six age groups of Wistar rats in a water maze spatial task to evaluate the effects of stress under different conditions. We found that the impairment or enhancement effect of an 'elevated platform' (EP) stress on memory was dependent on previous stress experience and on age. EP stress impaired memory retrieval in water maze naive animals. but enhanced rather than impaired memory retrieval in young water maze stress-experienced animals. Furthermore, exogenously applied corticosterone or foot shock stress before water maze training prevented the impairment of memory retrieval that should be induced by treatment with corticosterone or foot shock before the 'probe trial'. Again, memory retrieval was enhanced in young animals under these conditions, and this enhancement can be prevented by the glucocorticoid receptor antagonist RU 38486. Thus, glucocorticoid receptor activation not only induced impairment of memory but also increased the capacity of young animals to overcome a later stress. The present findings suggest that the effect of stress on memory can be switched from impairment to enhancement dependent on both stress experience and age.

Stress enables synaptic depression in CA1 synapses by acute and chronic morphine: Possible mechanisms for corticosterone on opiate addiction

The hippocampus, being sensitive to stress and glucocorticoids, plays significant roles in certain types of learning and memory. Therefore, the hippocampus is probably involved in the increasing drug use, drug seeking, and relapse caused by stress. We have studied the effect of stress with morphine on synaptic plasticity in the CA1 region of the hippocampus in vivo and on a delayed-escape paradigm of the Morris water maze. Our results reveal that acute stress enables long-term depression (LTD) induction by low-frequency stimulation (LFS) but acute morphine causes synaptic potentiation. Remarkably, exposure to an acute stressor reverses the effect of morphine from synaptic potentiation ( similar to 20%) to synaptic depression ( similar to 40%), precluding further LTD induction by LFS. The synaptic depression caused by stress with morphine is blocked either by the glucocorticoid receptor antagonist RU38486 or by the NMDA-receptor antagonist D-APV. Chronic morphine attenuates the ability of acute morphine to cause synaptic potentiation, and stress to enable LTD induction, but not the ability of stress in tandem with morphine to cause synaptic depression. Furthermore, corticosterone with morphine during the initial phase of drug use promotes later delayed-escape behavior, as indicated by the morphine-reinforced longer latencies to escape, leading to persistent morphine-seeking after withdrawal. These results suggest that hippocampal synaptic plasticity may play a significant role in the effects of stress or glucocorticoids on opiate addiction.

Stress within the postseizure time window inhibits seizure recurrence

Recurrence is a key characteristic in the development of epilepsy. It remains unclear whether seizure recurrence is sensitive to postseizure stress. Here, tonic-clonic seizures were induced with a convulsive dose of pentylenetetrazole (PTZ), and acute seizure recurrence was evoked with a subconvulsive dose of the drug. We found that stress inhibited seizure recurrence when applied 30 minutes or 2 hours, but not 4 hours, after the tonic-clonic seizure. The time-dependent anti-recurrence effect of stress was mimicked by the stress hormone corticosterone and blocked by co-administration of mineralocorticoid and glucocorticoid receptor antagonists. Furthermore, in a PTZ-induced epileptic kindling model, corticosterone administered 30 minutes after each seizure decreased the extent of seizures both during the kindling establishment and in the following challenge test. These results provide novel insights into both the mechanisms of and therapeutic strategies for epilepsy. (C) 2010 Elsevier Inc. All rights reserved.

Opioid Withdrawal for 4 Days Prevents Synaptic Depression Induced by Low Dose of Morphine or Naloxone in Rat Hippocampal CA1 Area In Vivo

The formation of memory is believed to depend on experience- or activity-dependent synaptic plasticity, which is exquisitely sensitive to psychological stress since inescapable stress impairs long-term potentiation (LTP) but facilitates long-term depression (LTD). Our recent studies demonstrated that 4 days of opioid withdrawal enables maximal extents of both hippocampal LTP and drug-reinforced behavior; while elevated-platform stress enables these phenomena at 18 h of opioid withdrawal. Here, we examined the effects of low dose of morphine (0.5 mg kg(-1), i.p.) or the opioid receptor antagonist naloxone (1 mg kg(-1), i.p.) on synaptic efficacy in the hippocampal CA1 region of anesthetized rats. A form of synaptic depression was induced by low dose of morphine or naloxone in rats after 18 h but not 4 days of opioid withdrawal. This synaptic depression was dependent on both N-methyl-D-aspartate receptor and synaptic activity, similar to the hippocampal long-term depression induced by low frequency stimulation. Elevated-platform stress given 2 h before experiment prevented the synaptic depression at 18 h of opioid withdrawal; in contrast, the glucocorticoid receptor (GR) antagonist RU38486 treatment (20 mg kg(-1), s.c., twice per day for first 3 days of withdrawal), or a high dose of morphine reexposure (15 mg kg(-1), s.c., 12 h before experiment), enabled the synaptic depression on 4 days of opioid withdrawal. This temporal shift of synaptic depression by stress or GR blockade supplements our previous findings of potentially correlated temporal shifts of LTP induction and drug-reinforced behavior during opioid withdrawal. Our results therefore support the idea that stress experience during opioid withdrawal may modify hippocampal synaptic plasticity and play important roles in drug-associated memory. (C) 2009 Wiley-Liss, Inc.

胚胎期光照和皮质酮对小鸡记忆影响的作用机制

It has been shown that prenatal light exposure and corticosterone improve memory retention of dark hatched chicks. The object of this study was to explore the neural mechanisms underlying the effect of prenatal light exposure and corticosterone on memory retention of chicks. To detect the effect of different prenatal treatments on memory retention of chicks, we used one-trial passive avoidance model. To examine the expression of glucocorticoid receptor (GR), neural cell adhesion molecule (NCAM), growth-associated protein 43 (GAP-43) and polysialic acid (PSA) in HV and LPO of chick brain, we used immunohistochemical method. Prenatal light exposure and glucocorticoid (corticosterone, dexamthesone) administered in embryonic day 20 (E20) markedly improve memory retention in dark hatched chicks. Light plays a critical role in improving memory. The critical exposure period is E19 and E20. The effect of these two hormones and light exposure can be significantly blocked by their receptor antagonist administration respectively. The light, corticosterone and particularly darkness significantly up-regulated the level of GR; the expression of NCAM and GAP-43 in HV and LPO peaked in E20 in normal hatched chicks and was significantly increased by light exposure and corticosterone. Protein synthesis inhibitor anisomycin markedly reduced the effect of light exposure but partially reduced the effect of corticosterone; light exposure and corticosterone in E20 significantly up-regulated PSA expression. Removing PSA from NCAM significantly retarded the effect of corticosterone on memory retention in chicks. Therefore, The effects of prenatal light exposure and corticosterone on memory retention are mediated via both corticosteroid receptors. The effects of both prenatal light and corticosterone might at first change the plasticity of the brain by up-regulation the synthesis and modification of proteins, and then influence the behavior performance of the chicks.

Measuring Receptor/Ligand Interaction at the Single-Bond Level: Experimental and Interpretative Issues

There is increased interest in measuring kinetic rates, lifetimes, and rupture forces of single receptor/ligand bonds. Valuable insights have been obtained from previous experiments attempting such measurements. However, it remains difficult to know with sufficient certainty that single bonds were indeed measured. Using exemplifying data, evidence supporting single-bond observation is examined and caveats in the experimental design and data interpretation are identified. Critical issues preventing definitive proof and disproof of single-bond observation include complex binding schemes, multimeric interactions, clustering, and heterogeneous surfaces. It is concluded that no single criterion is sufficient to ensure that single bonds are actually observed. However, a cumulative body of evidence may provide reasonable confidence. 0 2002 Biomedical Engineering Society.

Soluble Angiopoietin Receptor Tie-2 In Patients With Acute Myocardial Infarction And Its Detection By Optical Protein-Chip

The Tie-2 receptor has been shown to play a role in angiogenesis in atherosclerosis. The conventional method assaying the level of soluble Tie-2 (sTie-2) was ELISA. However, this method has some disadvantages. The aims of this research are to establish a more simple detection method, the optical protein-chip based on imaging ellipsomtry (OPC-IE) applying to Tie-2 assay. The sTie-2 biosensor surface on silicon wafer was prepared first, and then serum levels of sTie-2 in 38 patients with AMI were measured on admission (day 1), day 2, day 3 and day 7 after onset of chest pain and 41 healthy controls by ELISA and OPC-IE in parallel. Median level of sTie-2 increased significantly in the AMI patients when compared with the controls. Statistics showed there was a significant correlation in sTie-2 results between the two methods (r=0.923, P0.01). The result of this study showed that the level of sTie-2 increased in AMI, and OPC-IE assay was a fast, reliable, and convenient technique to measure sTie-2 in serum.

Parametric Analysis for Monitoring 2D Kinetics of Receptor-Ligand binding

Thermal fluctuation approach is widely used to monitor association kinetics of surface-bound receptor-ligand interactions. Various protocols such as sliding standard deviation (SD) analysis (SSA) and Page's test analysis (PTA) have been used to estimate two-dimensional (2D) kinetic rates from the time course of displacement of molecular carrier. In the current work, we compared the estimations from both SSA and modified PTA using measured data from an optical trap assay and simulated data from a random number generator. Our results indicated that both SSA and PTA were reliable in estimating 2D kinetic rates. Parametric analysis also demonstrated that such the estimations were sensitive to parameters such as sampling rate, sliding window size, and threshold. These results furthered the understandings in quantifying the biophysics of receptor-ligand interactions.

Molecular evolution of CXCR1, a G protein-coupled receptor involved in signal transduction of neutrophils

Human neutrophils are a type of white blood cell, which forms an early line of defense against bacterial infections. Neutrophils are highly responsive to the chemokine, interleukin-8 (IL-8) due to the abundant distribution of CXCR1, one of the IL-8 receptors on the neutrophil cell surface. As a member of the GPCR family, CXCR1 plays a crucial role in the IL-8 signal transduction pathway in neutrophils. We sequenced the complete coding region of the CXCR1 gene in worldwide human populations and five representative nonhuman primate species. Our results indicate accelerated protein evolution in the human lineage, which was likely caused by Darwinian positive selection. The sliding window analysis and the codon-based neutrality test identified signatures of positive selection at the N-terminal ligand/receptor recognition domain of human CXCR1.