Increased vulnerability to 6-hydroxydopamine lesion and reduced development of dyskinesias in mice lacking CB1 cannabinoid receptors

Motor impairment, dopamine (DA) neuronal activity and proenkephalin (PENK) gene expression in the caudate-putamen (CPu) were measured in 6-OHDA-lesioned and treated (l-DOPA + benserazide) CB1 KO and WT mice.A lesion induced by 6-OHDA produced more severe motor deterioration in CB1 KO mice accompanied by more loss of DA neurons and increased PENK gene expression in the CPu. Oxidative/nitrosative and neuroinflammatory parameters were estimated in the CPu and cingulate cortex (Cg). CB1 KO mice exhibited higher MDA levels and iNOS protein expression in the CPu and Cg compared to WT mice.Treatment with l-DOPA + benserazide (12 weeks) resulted in less severe dyskinesias in CB1 KO than in WT mice.The results revealed that the lack of cannabinoid CB1 receptors increased the severity of motor impairment and DA lesion, and reduced l-DOPA-induced dyskinesias. These results suggest that activation of CB1 receptors offers neuroprotection against dopaminergic lesion and the development of l-DOPA-induced dyskinesias.     

Dopaminergic enhancement of local food-seeking is under global homeostatic control

Recent work has implicated dopaminergic mechanisms in overeating and obesity with some researchers suggesting parallels between the dopamine dysregulation associated with addiction and an analogous dysregulation in obesity. The precise role of dopamine in mediating reward and reinforcement, however, remains controversial. In contrast to drugs of abuse, pursuit of a natural reward, such as food, is regulated by homeostatic processes that putatively maintain a stable energy balance keeping unrestrained consumption and reward pursuit in check. Understanding how the reward system is constrained by or escapes homeostatic regulation is a critical question. The widespread use of food restriction to motivate animal subjects in behavior paradigms precludes investigation of this relationship as the homeostatic system is locked into deficit mode. In the present study, we examined the role of dopamine in modulating adaptive feeding behavior in semi-naturalistic homecage paradigms where mice earn all of their food from lever pressing. We compared consumption and meal patterning between hyperdopaminergic dopamine transporter knock-down and wild-type mice in two paradigms that introduce escalating costs for procuring food. We found that hyperdopaminergic mice exhibited similar demand elasticity, weight loss and energy balance in response to cost. However, the dopamine transporter knock-down mice showed clear differences in meal patterning. Consistent with expectations of enhanced motivation, elevated dopamine increased the meal size and reduced intrameal cost sensitivity. Nonetheless, this did not alter the overall energy balance. We conclude that elevated dopamine enhances the incentive or willingness to work locally within meals without shifting the energy balance, enhancing global food-seeking or generating an energy surplus.     

Altered Expression of Tyrosine Hydroxylase in the Locus Coeruleus Noradrenergic System in Citalopram Neonatally Exposed Rats and Monoamine Oxidase A Knock Out Mice

In rodents, noradrenergic (NE) locus coeruleus (LC) neurons are well known to express tyrosine hydroxylase (TH) immunoreactivity. However, due to its very low enzyme activity, NE cortical fibers do not typically express TH immunoreactivity, thus dopamine‐β‐hydroxylase (DBH) immunoreactivity is commonly utilized as a marker for NE cortical fibers. In this study, we performed double and/or triple immunofluorescent staining using antibodies against TH, DBH, and/or norepinephrine transporter (NET) to investigate the altered NE TH expression of cortical fibers in citalopram (CTM)‐exposed rats and monoamine oxidase (MAO) A knock out (KO) mice. We have noted the following novel findings: (1) neonatal exposure to the selective serotonin reuptake inhibitor (SSRI) CTM enhanced NE TH immunoreactive fibers throughout the entire neocortex, and a few of them appeared to be hypertrophic; (2) slightly enhanced NE cortical TH immunoreactive fibers were also noted in MAO A KO mice, and many of them revealed varicosities compared with the rather smooth NE cortical TH immunoreactive fibers in wild‐type (WT) mice; (3) LC dendrites of MAO A KO mice exhibited beaded morphology compared with the smooth LC dendrites in WT mice. Our findings suggest that both genetic and environmental factors during early development may play a critical role in the regulation and proper function of NE TH expression in the neocortex. Anat Rec, 2011. © 2011 Wiley‐Liss, Inc.     

Pyroglutamate-Aβ 3 and 11 colocalize in amyloid plaques in Alzheimer's disease cerebral cortex with pyroglutamate-Aβ 11 forming the central core

N-terminal truncated amyloid beta (Aβ) derivatives, especially the forms having pyroglutamate at the 3 position (AβpE3) or at the 11 position (AβpE11) have become the topic of considerable study. AβpE3 is known to make up a substantial portion of the Aβ species in senile plaques while AβpE11 has received less attention. We have generated very specific polyclonal antibodies against both species. Each antibody recognizes only the antigen against which it was generated on Western blots and neither recognizes full length Aβ. Both anti-AβpE3 and anti-AβpE11 stain senile plaques specifically in Alzheimer's disease cerebral cortex and colocalize with Aβ, as shown by confocal microscopy. In a majority of plaques examined, AβpE11 was observed to be the dominant form in the innermost core. These data suggest that AβpE11 may serve as a generating site for senile plaque formation.     

超促排卵过程中抗苗勒管激素动态变化及其与临床结局的相关性

目的探讨血清及卵泡液(follicular fluid,FF)中抗苗勒管激素(AMH)在控制性超促排卵(COH)过程中的动态变化及其与COH结局的相关性分析。方法选取因输卵管因素和/或男方因素行体外受精/卵胞质内单精子注射-胚胎移植(IVF/ICSI-ET)的周期,随机分为长方案组(n=38)和非降调节组(n=38)。长方案组和非降调节组分别于前一月经周期第2或第3日(基础日)、降调节期间月经第2或第3日、促性腺激素(Gn)启动日、Gn启动第5日(Gn5)、诱发排卵日(h CG注射日)、取卵前1日和取卵后3 d抽取外周静脉血。取卵日收集直径≥18 mm(大)、14~17 mm(中)、14 mm(小)的FF。结果降调节后血清AMH水平在Gn启动日较基础日显著升高,2种COH方案随外源性Gn使用时间的增加血清AMH降低;随卵泡直径增大,FF中AMH降低。Gn5血清AMH与获卵数、MⅡ卵数和可利用胚胎数相关性最强,中FF的AMH与窦卵泡数(AFC)、Gn用量和可利用胚胎相关性较好。结论降调节显著升高AMH水平,增加可募集AFC及改善卵泡发育同步化,提示可依此调整Gn用量,外源性Gn使用后AMH水平逐渐降低;Gn5血清AMH水平可预测IVF/ICSI-ET结局。     

Colesteatoma: influencia de la técnica quirúrgica y el estadio EAONO/JOS en los resultados audiológicos

Introduction and objectiveThe treatment of cholesteatoma is surgical in most cases. When it is indicated, it is preferable to choose a reconstructive surgical technique with the dual purpose of eradicating the disease and preserving or improving the patient's hearing. In 2017, the European Academy of Otology and Neuro-Otology/Japanese Otological Society (EAONO/JOS) published a new cholesteatoma classification. The aims of this study are to determine the influence of the surgical technique use and this classification on patient's hearing outcomes.MethodsA retrospective study that include patients who underwent reconstructive surgery of cholesteatoma between 2012 and 2017 is carried out. Based on pre-surgical computed tomography (CT) images, disease is staged according to the EAONO/JOS classification. Hearing outcomes obtained by pre and postoperative pure tone audiometry are analysed according to the surgical technique used and according to the stage of the disease.Results143 patients with no statistically significant differences in hearing thresholds before surgery are included. One year after surgery, all the patients’ airbone pure tone average (PTA) and mean differential auditory threshold have improved significantly (P = .01 and P = .001). Those patients who undergo tympanoplasty with two-stage canal wall up mastoidectomy presente better postsurgical air PTA and postsurgical mean differential auditory threshold outcomes (P = .007 and P = .014) than those patients who underwent tympanoplasty with canal wall down mastoidectomy. Moreover, the patients who underwent tympanoplasty with two-stage canal wall up mastoidectomy had improved airbone PTA and mean differential auditory threshold one year after the surgery with statistical significance (P = .001 and P = .013). The mean differential auditory threshold is also better (P = .008) in the patients who undergo tympanoplasty with canal wall down mastoidectomy one year after the procedure.ConclusionsReconstructive surgical techniques improve hearing one year after surgery. In our study, this improvement is significantly greater with tympanoplasty with two-stage canal wall up mastoidectomy.     

The role of top‐down spatial attention in contingent attentional capture

It is well known that attentional capture by an irrelevant salient item is contingent on top‐down feature selection, but whether attentional capture may be modulated by top‐down spatial attention remains unclear. Here, we combined behavioral and ERP measurements to investigate the contribution of top‐down spatial attention to attentional capture under modified spatial cueing paradigms. Each target stimulus was preceded by a peripheral circular cue array containing a spatially uninformative color singleton cue. We varied target sets but kept the cue array unchanged among different experimental conditions. When participants’ task was to search for a colored letter in the target array that shared the same peripheral locations with the cue array, attentional capture by the peripheral color cue was reflected by both a behavioral spatial cueing effect and a cue‐elicited N2pc component. When target arrays were presented more centrally, both the behavioral and N2pc effects were attenuated but still significant. The attenuated cue‐elicited N2pc was found even when participants focused their attention on the fixed central location to identify a colored letter among an RSVP letter stream. By contrast, when participants were asked to identify an outlined or larger target, neither the behavioral spatial cueing effect nor the cue‐elicited N2pc was observed, regardless of whether the target and cue arrays shared same locations or not. These results add to the evidence that attentional capture by salient stimuli is contingent upon feature‐based task sets, and further indicate that top‐down spatial attention is important but may not be necessary for contingent attentional capture.     

Attentional capture by size singletons is determined by top-down search goals

The question whether attentional capture by salient visual stimuli is driven by bottom-up salience or is contingent on top-down task set is still under dispute. We show that the ability of size singletons to capture attention is determined by current search goals. Participants searched for small or large target singletons among medium-size distractors. Attentional capture by small or large size singleton cues that preceded target search displays was reflected by spatial cueing effects and N2pc components. These effects were observed only when these cues matched the current target-defining feature, but not for physically identical but mismatching cues. Results demonstrate that attentional capture by size singletons is not driven by bottom-up salience, but is controlled by feature-specific task settings.     

Analgesia induced by self‐initiated electrotactile sensation is mediated by top‐down modulations

It is well known that sensory perception can be attenuated when sensory stimuli are controlled by self‐initiated actions. This phenomenon is explained by the consistency between forward models of anticipated action effects and actual sensory feedback. Specifically, the brain state related to the binding between motor processing and sensory perception would have inhibitory function by gating sensory information via top‐down control. Since the brain state could casually influence the perception of subsequent stimuli of different sensory modalities, we hypothesize that pain evoked by nociceptive stimuli following the self‐initiated tactile stimulation would be attenuated as compared to that following externally determined tactile stimulation. Here, we compared psychophysical and neurophysiological responses to identical nociceptive‐specific laser stimuli in two different conditions: self‐initiated tactile sensation condition (STS) and nonself‐initiated tactile sensation condition (N‐STS). We observed that pain intensity and unpleasantness, as well as laser‐evoked brain responses, were significantly reduced in the STS condition compared to the N‐STS condition. In addition, magnitudes of alpha and beta oscillations prior to laser onset were significantly larger in the STS condition than in the N‐STS condition. These results confirmed that pain perception and pain‐related brain responses were attenuated when the tactile stimulation was initiated by subjects’ voluntary actions, and exploited neural oscillations reflecting the binding between motor processing and sensory feedback. Thus, our study elaborated the understanding of underlying neural mechanisms related to top‐down modulations of the analgesic effect induced by self‐initiated tactile sensation, which provided theoretical basis to improve the analgesic effect in various clinical applications.     

Root canal preparation with the NiTi systems K3, Mtwo and ProTaper

The aim of this paper was to examine the result of rotary root canal preparation with the nickel-titanium (NiTi) systems K3, ProTaper and Mtwo. One hundred and fifty curved artificial root canals and 60 mesial canals of human mandibular molars were selected. In the group of curved artificial canals, all canals were prepared to size 35/0.04 taper with the three systems. In the group of human mandibular molars, the teeth with mature root canals were radiographed with silver points inserted in bucco-lingual and in mesio-distal positions. In the artificial root group, one K3 instrument separated. Mtwo (20%) showed significantly (P = 0.003) less zips than K3 (46.9%) or ProTaper (50%). There were no significant differences in ledge and elbow formation. K3 and Mtwo had the lowest percentage of canal transportation. There was no significant difference regarding the preparation length or the condition of the apical foramina following the preparation. Canals prepared with K3 (26.5%) were significantly (P < 0.001) less tapered than ProTaper (62%) and Mtwo (82%). In the human mandibular molar group, one Mtwo and one ProTaper instrument separated. No significant differences were found in the preparation length, transportation or taper. The three systems tested, K3, Mtwo and ProTaper, achieved good preparation results.