Inter-ictal assay of peripheral circulating inflammatory mediators in migraine patients under adjunctive cervical non-invasive vagus nerve stimulation (nVNS): A proof-of-concept study

Objective

To assay peripheral inter-ictal cytokine serum levels and possible relations with non-invasive vagus nerve stimulation (nVNS) responsiveness in migraineurs.

Interaction of nicotinic acetylcholine receptors with dopamine receptors in synaptic plasticity of the mouse insular cortex

The insular cortex plays essential roles in nicotine addiction. However, much is still unknown about its cellular and synaptic mechanisms responsible for nicotine addiction. We have previously shown that in layer 5 pyramidal neurons of the mouse insular cortex, activation of the nicotinic acetylcholine receptors (nAChRs) suppresses synaptic potentiation through enhancing GABAergic synaptic transmission, although it enhances both glutamatergic and GABAergic synaptic transmission. In the present study, we examined whether dopamine receptors might contribute to the nicotine‐induced inhibition of synaptic potentiation. The nicotine‐induced inhibition of synaptic potentiation was decreased in the presence of a D1 dopamine receptor antagonist SCH23390 irrespective of the presence of a D2 dopamine receptor antagonist sulpiride, suggesting that D1 dopamine receptors are involved in nicotine‐induced inhibition. We also investigated how dopamine receptors might contribute to the nAChR‐induced enhancement of glutamatergic and GABAergic synaptic transmission. The nAChR‐induced enhancement of GABAergic synaptic transmission was decreased in the presence of SCH23390 irrespective of the presence of sulpiride, whereas that of glutamatergic synaptic transmission was not altered in the presence of SCH23390 and sulpiride. These results suggest that D1 dopamine receptors are involved in the nAChR‐induced enhancement of GABAergic synaptic transmission while dopamine receptors are not involved in that of glutamatergic synaptic transmission. These observations indicate that the interaction between nAChRs and D1 dopamine receptors plays critical roles in synaptic activities in layer 5 pyramidal neurons of the mouse insular cortex. These insular synaptic changes might be associated with nicotine addiction.     

Host–microbiome interactions: the aryl hydrocarbon receptor as a critical node in tryptophan metabolites to brain signaling

ABSTRACT

Tryptophan (Trp) is not only a nutrient enhancer but also has systemic effects. Trp metabolites signaling through the well-known aryl hydrocarbon receptor (AhR) constitute the interface of microbiome-gut-brain axis. However, the pathway through which Trp metabolites affect central nervous system (CNS) function have not been fully elucidated. AhR participates in a broad variety of physiological and pathological processes that also highly relevant to intestinal homeostasis and CNS diseases. Via the AhR-dependent mechanism, Trp metabolites connect bidirectional signaling between the gut microbiome and the brain, mediated via immune, metabolic, and neural (vagal) signaling mechanisms, with downstream effects on behavior and CNS function. These findings shed light on the complex Trp regulation of microbiome-gut-brain axis and add another facet to our understanding that dietary Trp is expected to be a promising noninvasive approach for alleviating systemic diseases.     

AN UNUSUAL BILATERAL VAGAL PARAGANGLIOMAS： ONE CASE STUDY

VAGAL paraganglioma VP)is an uncommonneoplasm originating from neural crest paragan-glion cells located along the vagus nerve,repre-senting less than5%of all paragangliomas of the head andneck.1Despite improvement in microsurgical techniques,management of…     

LKB1表达下调对培养海马神经元突触mEPSC的影响

目的研究离体培养的海马神经元LKB1表达下调对于神经元微小兴奋性突触后电流(mEP-SC)的影响。方法选用17d的胚胎大鼠培养海马神经元,分别用电穿孔的方法转染CAG-RE质粒和LKB1RNAi质粒,培养10~12d后进行电生理记录,选用全细胞膜片钳方式及自由记录模式,细胞外液加TTX阻断动作电位,加Bicucullin抑制GABA电流,记录神经元的mEPSC,比较2组神经元的mEPSC频率和幅度的差别。结果转染CAG-RE的神经元mEPSC幅度平均为25.6pA,频率平均为(5.21±0.25)Hz,是基线的99.8%;转染LKB1RNAi的神经元mEPSC幅度平均为35.1pA,频率平均为(5.79±0.27)Hz,是基线的127.1%;比较2组间频率、幅度变化,差别有显著性意义(P<0.05)。结论LKB1基因表达下调增强了培养海马神经元突触传递的效率。     

γ-干扰素对大鼠胚胎基底前脑及隔区核团胆碱能神经元分化的影响

为了研究γ-干扰素(IFNγ)对大鼠胚胎基底前脑及隔区核团胆碱能神经元分化的作用,采用免疫组织化学方法对胆碱能神经元的特异性标记酶-胆碱乙酰基转移酶(ChAT)进行染色,ChAT阳性细胞的数量反映了胆碱能神经元的数量,并用14C-乙酰CoA作底物来检测ChAT活性。结果显示,IFNγ处理过的实验组,ChAT阳性细胞数量显著增加,ChAT活性也增加,这种增加被大鼠抗小鼠IFNγ单克隆抗体(Ab-IFNγ)完全拮抗。采用流式细胞术对细胞周期进行分析,细胞周期及细胞百分率无明显改变。用MAP2标记神经细胞,神经细胞数基本未增加。以上结果提示:IFNγ不能促进基底前脑和隔区神经元增殖,胆碱能神经元表达增加不是因为神经元数目增加而是分化的结果。     

丹参对持续癫痫幼鼠脑损伤保护作用的实验研究

目的 探讨丹参对持续癫痫发作诱发幼鼠脑神经元损伤是否具有保护作用。方法 皮下及腹腔注射贝美格针诱发健康幼龄鼠癫痫持续状态发作。光镜下观察神经元病变情况；电镜观察海马神经元超微结构的改变。结果 持续癫痴组幼鼠脑组织光镜下可见明显的神经元病变。电镜下可见海马区神经元的超微结构病变。丹参治疗组神经元病变均轻于持续癫痴组；而正常对照组未见类似病变。结论 丹参在组织、细胞和亚细胞水平对持续癫病幼鼠脑神经元损伤具有一定的保护作用，为临床有效防治小儿惊厥性脑损伤提供了可靠的实验依据。     

l-DOPA induces concentration-dependent facilitation and inhibition of presynaptic acetylcholine release in the guinea-pig submucous plexus

Neurotransmitter- or neuromodulator-like actions ofl-DOPA were investigated with intracellular recordings from submucous plexus neurons of the guinea-pig caecum.l-DOPA at 30 nM augmented the amplitude of fast EPSPs, but did not affect depolarizations elicited by puff application of acetylcholine (ACh). The augmenting effect ofl-DOPA on the fast EPSPs was counteracted byl-DOPA methyl ester. The fast EPSPs were depressed by 10 μMl-DOPA, but transiently augmented after rinsing the drug.l-DOPA methyl ester did not affect the inhibitory action ofl-DOPA on the fast EPSPs, but antagonized the potentiation following the inhibition. The depolarization elicited by exogenously applied. ACh was inhibited by 10 μMl-DOPA. Intracellular Ca²⁺ concentrations ([Ca²⁺]_i) of the neuronal soma were measured with fura-2 microfluorophotometry. The transient increase in the [Ca²⁺]_i evoked by the somatic action potential (Δ[Ca²⁺]_AP) was facilitated by 30 nMl-DOPA, but decreased by the drug at 10 μM. It is concluded thatl-DOPA at low concentrations enhances the Δ[Ca²⁺]_AP, increasing the neurotransmitter release, but at high dose diminishes the Δ[Ca²⁺]_AP, inhibiting the neurotransmission.     

Monolateral hypoplasia of the motor vagal nuclei in a case of sudden infant death syndrome

During the development of motor vagal nuclei (MVN), the neuroblasts of the myeloencephalic basal plate migrate in the dorsolateral direction to form the dorsal motor vagal nucleus (DMVN) and ventrolaterally to form the ventral motor vagal nucleus (VMVN). Those neuroblasts that remain close to the median sulcus will form the hypoglossal nucleus. In support of the congenital origin of the alteration of the MVN in sudden infant death syndrome (SIDS), we report the case of an 8‐month‐old female child who was found dead in her cot. The neuropathological assessment revealed that the medullary triangle of the 4th ventricle floor was asymmetric, owing to the presence of three prominences to the left side of the median sulcus. The medial prominence corresponded to the hypoglossal nucleus, which showed a marked increase in the number of large neurons; the intermediate prominence corresponded to the DMVN whose large neurons were reduced and were recognizable mainly at the level of the medial fringe; the lateral prominence corresponded to the solitary nucleus. The left solitary tract showed a reduction of the transverse diameter. Also, the left VMVN showed marked reduction in the number of neurons. Inflammatory and astrocytic reactions were absent. We suggest that in SIDS cases the hypocellularity of the MVN and the increased number of neurons of the hypoglossal nucleus are intimately related, indicating a congenital alteration due to incomplete migration of the vagal neuroblasts with abnormality of the autonomic cardio‐respiratory control.