Transient and sustained effects of dopamine and serotonin signaling in motivation‐related behavior

Pharmacological studies of antidepressants and atypical antipsychotics have suggested a role of dopamine and serotonin signaling in depression. However, depressive symptoms and treatment effects are difficult to explain based simply on brain‐wide decrease or increase in the concentrations of these molecules. Recent animal studies using advanced neuronal manipulation and observation techniques have revealed detailed dopamine and serotonin dynamics that regulate diverse aspects of motivation‐related behavior. Dopamine and serotonin transiently modulate moment‐to‐moment behavior at timescales ranging from sub‐second to minutes and also produce persistent effects, such as reward‐related learning and stress responses that last longer than several days. Transient and sustained effects often exhibit specific roles depending on the projection sites, where distinct synaptic and cellular mechanisms are required to process the neurotransmitters for each transient and sustained timescale. Therefore, it appears that specific aspects of motivation‐related behavior are regulated by distinct synaptic and cellular mechanisms in specific brain regions that underlie the transient and sustained effects of dopamine and serotonin signaling. Recent clinical studies have implied that subjects with depressive symptoms show impaired transient and sustained signaling functions; moreover, they exhibit heterogeneity in depressive symptoms and neuronal dysfunction. Depressive symptoms may be explained by the dysfunction of each transient and sustained signaling mechanism, and distinct patterns of impairment in the relevant mechanisms may explain the heterogeneity of symptoms. Thus, detailed understanding of dopamine and serotonin signaling may provide new insight into depressive symptoms.     

丙泊酚麻醉对老龄大鼠认知功能和海马神经元γ-氨基丁酸A受体表达的影响

目的观察丙泊酚麻醉对老龄大鼠认知功能及海马神经元γ-氨基丁酸A(GABA)受体表达的影响。方法50只SD老年大鼠随机分为丙泊酚组和对照组,每组25只。丙泊酚组大鼠腹腔注射1%丙泊酚中/长链脂肪乳注射液6 mL/kg,对照组腹腔注射等体积的生理盐水。麻醉后1 d进行Morris水迷宫实验,分别采用HE染色和尼氏体染色观察海马区神经细胞及尼氏体(Nissl体)形态学变化,Western Blot检测GABA蛋白量表达。结果麻醉后,2组大鼠肛温、心率、呼吸频率、血氧饱和度比较,差异均无统计学意义(P>0.05)。随着实验时间的延长,2组大鼠逃逸潜伏期、总里程数逐渐减小,丙泊酚组大鼠各时间点逃逸潜伏期、总里程均高于对照组,差异有统计学意义(P<0.05)。丙泊酚组大鼠穿越平台区域次数、时间小于、短于对照组,差异有统计学意义(P<0.05)。对照组海马区Nissl体存在于细胞浆及树突,染色较深,神经细胞排列整齐,形态规则;丙泊酚组Nissl体消失,神经细胞数量减少,细胞核破裂、丢失。丙泊酚组大鼠海马GABA蛋白表达量低于对照组,差异有统计学意义(P<0.05)。结论丙泊酚对大鼠认知功能有影响,并与海马区GABA的表达相关。     

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.     

Sensory evoked potentials in patients with Rett syndrome through the lens of animal studies: Systematic review

ObjectiveSystematically review the abnormalities in event related potential (ERP) recorded in Rett Syndrome (RTT) patients and animals in search of translational biomarkers of deficits related to the particular neurophysiological processes of known genetic origin (MECP2 mutations).MethodsPubmed, ISI Web of Knowledge and BIORXIV were searched for the relevant articles according to PRISMA standards.ResultsERP components are generally delayed across all sensory modalities both in RTT patients and its animal model, while findings on ERPs amplitude strongly depend on stimulus properties and presentation rate. Studies on RTT animal models uncovered the abnormalities in the excitatory and inhibitory transmission as critical mechanisms underlying the ERPs changes, but showed that even similar ERP alterations in auditory and visual domains have a diverse neural basis. A range of novel approaches has been developed in animal studies bringing along the meaningful neurophysiological interpretation of ERP measures in RTT patients.ConclusionsWhile there is a clear evidence for sensory ERPs abnormalities in RTT, to further advance the field there is a need in a large-scale ERP studies with the functionally-relevant experimental paradigms.SignificanceThe review provides insights into domain-specific neural basis of the ERP abnormalities and promotes clinical application of the ERP measures as the non-invasive functional biomarkers of RTT pathophysiology.     

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。     

Blunted renal dopaminergic system activity in puromycin aminonucleoside-induced nephrotic syndrome.

BACKGROUND: A primary tubular sodium handling abnormality has been implicated in the edema formation of nephrotic syndrome. Dopamine synthesized by renal proximal tubules behaves as an endogenous natriuretic hormone by activating D(1)-like receptors as a paracrine/autocrine substance. METHODS: We examined the time courses of the urinary excretion of sodium, protein and dopamine in puromycin aminonucleoside (PAN)-treated and control rats. The rats were sacrificed during greatest sodium retention (day 7) as well as during negative sodium balance (day 14) for the evaluation of renal aromatic l-amino acid decarboxylase (AADC) activity, the enzyme responsible for the synthesis of renal dopamine. Also, the influence of volume expansion (VE) and the effects of the D(1)-like agonist fenoldopam (10 microg/kg bw/min) on natriuresis and on proximal tubular Na(+),K(+)-ATPase activity were examined on day 7. RESULTS: The daily urinary excretion of dopamine was decreased in PAN-treated rats, from day 5 and beyond. This was accompanied by a marked decrease in the renal AADC activity, on days 7 and 14. During VE, the fenoldopam-induced decrease in proximal tubular Na(+),K(+)-ATPase activity was more pronounced in PAN-treated rats than in controls. However, the urinary sodium excretion during fenoldopam infusion was markedly increased in control rats but was not altered in PAN-treated animals. CONCLUSION: PAN nephrosis is associated with a blunted renal dopaminergic system activity which may contribute to enhance the proximal tubular Na(+),K(+)-ATPase activity. However, the lack of renal dopamine appears not to be related with the overall renal sodium retention in a state of proteinuria.     

多巴胺受体与其他血压调节系统的交互作用在高血压研究中的地位

肾脏是人体负责钠排泄的重要器官,多巴胺由于其强大的抑制肾脏钠重吸收作用而在原发性高血压的发生、发展中发挥重要作用。多巴胺受体的5个亚型均直接或间接通过与其他血压调节系统的交互作用,参与肾脏钠通道或血压的调节。现就多巴胺受体在调节机体血压和肾脏利钠、利尿作用中所发挥的重要作用作一综述。