Establishment of a scoring model for the differential diagnosis of white coat hypertension and sustained hypertension.

OBJECTIVES: This study aimed to establish a scoring model for the differential diagnosis of white coat hypertension (WCH) and sustained hypertension (SHT). METHODS: This study comprised 553 adults with elevated office blood pressure, normal renal function, and no antihypertensive medications. Through questionnaire investigation and biochemical detection, 17 parameters, such as gender and age, were acquired. WCH and SHT were distinguished by 24 h ambulatory blood pressure monitoring. The participants were randomly divided into a training set (445 cases) and a validation set (108 cases). The above parameters were screened using least absolute shrinkage and selection operator regression and univariate logistic regression analysis in the training set. Afterward, a scoring model was constructed through multivariate logistic regression analysis. RESULTS: Finally, six parameters were selected, including isolated systolic hypertension, office systolic blood pressure, office diastolic blood pressure, triglyceride, serum creatinine, and cardiovascular and cerebrovascular diseases. Multivariate logistic regression was used to establish a scoring model. The R2 and area under the ROC curve (AUC) of the scoring model in the training set were 0.163 and 0.705, respectively. In the validation set, the R2 of the scoring model was 0.206, and AUC was 0.718. The calibration test results revealed that the scoring model had good stability in both the training and validation sets (mean square error = 0.001, mean absolute error = 0.014; mean square error = 0.001, mean absolute error = 0.025). CONCLUSION: A stable scoring model for distinguishing WCH was established, which can assist clinicians in identifying WCH at the first diagnosis.

Bidirectional modulation of hippocampal synaptic plasticity by Dopaminergic D4-receptors in the CA1 area of hippocampus.

Long-term potentiation (LTP) is the persistent increase in the strength of the synapses. However, the neural networks would become saturated if there is only synaptic strenghthening. Synaptic weakening could be facilitated by active processes like long-term depression (LTD). Molecular mechanisms that facilitate the weakening of synapses and thereby stabilize the synapses are also important in learning and memory. Here we show that blockade of dopaminergic D4 receptors (D4R) promoted the formation of late-LTP and transformed early-LTP into late-LTP. This effect was dependent on protein synthesis, activation of NMDA-receptors and CaMKII. We also show that GABAA-receptor mediated mechanisms are involved in the enhancement of late-LTP. We could show that short-term plasticity and baseline synaptic transmission were unaffected by D4R inhibition. On the other hand, antagonizing D4R prevented both early and late forms of LTD, showing that activation of D4Rs triggered a dual function. Synaptic tagging experiments on LTD showed that D4Rs act as plasticity related proteins rather than the setting of synaptic tags. D4R activation by PD 168077 induced a slow-onset depression that was protein synthesis, NMDAR and CaMKII dependent. The D4 receptors, thus exert a bidirectional modulation of CA1 pyramidal neurons by restricting synaptic strengthening and facilitating synaptic weakening.

Stimulation of Synaptic Vesicle Exocytosis by the Mental Disease Gene DISC1 is Mediated by N-Type Voltage-Gated Calcium Channels.

Lesions and mutations of the DISC1 (Disrupted-in-schizophrenia-1) gene have been linked to major depression, schizophrenia, bipolar disorder and autism, but the influence of DISC1 on synaptic transmission remains poorly understood. Using two independent genetic approaches-RNAi and a DISC1 KO mouse-we examined the impact of DISC1 on the synaptic vesicle (SV) cycle by population imaging of the synaptic tracer vGpH in hippocampal neurons. DISC1 loss-of-function resulted in a marked decrease in SV exocytic rates during neuronal stimulation and was associated with reduced Ca(2+) transients at nerve terminals. Impaired SV release was efficiently rescued by elevation of extracellular Ca(2+), hinting at a link between DISC1 and voltage-gated Ca(2+) channels. Accordingly, blockade of N-type Cav2.2 channels mimics and occludes the effect of DISC1 inactivation on SV exocytosis, and overexpression of DISC1 in a heterologous system increases Cav2.2 currents. Collectively, these results show that DISC1-dependent enhancement of SV exocytosis is mediated by Cav2.2 and point to aberrant glutamate release as a probable endophenotype of major psychiatric disorders.

Hippocampal synaptic metaplasticity requires the activation of NR2B-containing NMDA receptors.

The potential to exhibit synaptic plasticity itself is modulated by previous synaptic activity, which has been termed as metaplasticity. In this paper, we demonstrated that the activation of N-methyl-d-aspartate (NMDA) receptor 2B (NR2B) subunit in NNDA receptors was required for hippocampal metaplasticity at Schaffer collateral-commissural fiber-CA1 synapses. Brief 5 Hz priming stimulation did not cause long-term synaptic plasticity; however, it could result in the inhibition of subsequently evoked long-term potentiation (LTP). Meanwhile, the application of selective antagonists for NR2B subunit of NMDA receptors after delivering priming stimulation could block the metaplasticity. In contrast, LTP induction was not affected by NR2B antagonists in slices without pre-treatment of priming stimulation. These results indicated that the activation of NR2B-containing NMDA receptors was required for metaplasticity.

Hippocampal endocannabinoids play an important role in induction of long-term potentiation and regulation of contextual fear memory formation.

Recent studies show contradictory results regarding the contribution of endocannabinoids in fear memory formation and long-term synaptic plasticity. In this study, we investigated the effects of both cannabinoid receptor type 1 (CB1 receptor) antagonist AM281 and anandamide reuptake inhibitor AM404 on the formation of contextual fear memory in adult mice. Both i.p. and intra-hippocampal injections of AM281 promoted contextual fear memory while a high dose of AM404 inhibited it. These findings demonstrate that CB1 receptor-mediated signaling negatively contributes to contextual fear memory formation. We further investigated the induction of long-term potentiation (LTP) in CA1 pyramidal neurons of hippocampal slices and found that AM281 impaired the induction of LTP. Additionally, the blockade of LTP by AM281 was completely prevented by bath application of picrotoxin, a selective antagonist of GABA(A) receptor. Taken together, these results indicate that activation of CB1 receptor contributes to induction of LTP via a GABA(A) receptor-mediated mechanism.