Subcortical shape alterations in major depressive disorder: Findings from the ENIGMA major depressive disorder working group

Alterations in regional subcortical brain volumes have been investigated as part of the efforts of an international consortium, ENIGMA, to identify reliable neural correlates of major depressive disorder (MDD). Given that subcortical structures are comprised of distinct subfields, we sought to build significantly from prior work by precisely mapping localized MDD-related differences in subcortical regions using shape analysis. In this meta-analysis of subcortical shape from the ENIGMA-MDD working group, we compared 1,781 patients with MDD and 2,953 healthy controls (CTL) on individual measures of shape metrics (thickness and surface area) on the surface of seven bilateral subcortical structures: nucleus accumbens, amygdala, caudate, hippocampus, pallidum, putamen, and thalamus. Harmonized data processing and statistical analyses were conducted locally at each site, and findings were aggregated by meta-analysis. Relative to CTL, patients with adolescent-onset MDD (≤ 21 years) had lower thickness and surface area of the subiculum, cornu ammonis (CA) 1 of the hippocampus and basolateral amygdala (Cohen's d = ?0.164 to ?0.180). Relative to first-episode MDD, recurrent MDD patients had lower thickness and surface area in the CA1 of the hippocampus and the basolateral amygdala (Cohen's d = ?0.173 to ?0.184). Our results suggest that previously reported MDD-associated volumetric differences may be localized to specific subfields of these structures that have been shown to be sensitive to the effects of stress, with important implications for mapping treatments to patients based on specific neural targets and key clinical features.     

Predictors of the conservative management outcomes in patients with lumbar herniated nucleus pulposus: A prospective study in Indonesia

BackgroundThe objective of this study was to identify the predictors of the conservative management outcomes in patients with lumbar herniated nucleus pulposus (HNP).MethodsA prospective study was conducted between June 2010 and April 2012 in Banda Aceh, Indonesia. Clinical and baseline neurologic examinations such as passive straight leg raising test (SLRT), cross SLRT, and patellar and Achilles reflexes were assessed prior to the conservative management. The patients were evaluated at 2nd, 4th, 8th, 12th and 24th week following commencement of the conservative management.ResultsWe recruited and followed 171 HNP patients of which 35.7% of them had good outcome. At univariate analysis, patients with more than 12 months duration of complaint, those with dominant radicular pain, severe pain intensity (visual analogue scale 7–10), positive SLRT, positive cross SLRT, and reduced motor power of knee extensors (muscle strength grade 1–4), were associated with poor outcome. Multivariate analysis suggested that patients with dominant radicular type of pain were likely to had poor outcome compared to those with dominant back pain (odd ratio (OR) 10.57 with 95% confidence interval (CI) 1.15–96.93). Patients with reduced motor power of knee extensors also had a higher chance to have poor outcome compared to those who were normal (OR: 10.57; 95% CI: 1.15–96.93).ConclusionType of pain and the strength of lower extremities could be able to predict the failure of conservative management in patients with lumbar disc herniation. However, further studies with the bigger sample size are warrant to validate our results.     

Nucleus Detection on Pap Smear Images for Cervical Cancer Diagnosis: A Review Analysis

Cervical cancer is a cell disease in the cervix that develops out of control in the female body. The cervix links the vagina (birth canal) with the upper section of the uterus, which can only be found in the female body. This is the second leading cause of death among women around the world. However, cervical cancer is currently one of the most preventable cancers if early detection is identified. The effect of unidentified cancer may increase the risk of death when the cell disease spreads to other parts of the female anatomy (metastasize). The Papanicolaou test is a cervical cancer screening technique used to identify potentially precancerous and cancerous cells in women’s cervix. In this paper, a few popular detection method was applying and experimented on pap smear images. A few image quality assessment (IQA) was obtained in order to determine the best of detection method. The nucleus detection will help pathologists to diagnosis in early stages of cancer. The early detection is very important stage in order to reduce the cancer incidence and mortality. The method that needs to be invented in this study is the detection method. Image detection is the process of partitioning the image into multiple regions. The detection method is object detection and recognition as well as the boundary in images. The segmented Pap Smear image is one of the detection tools with many different methods that generated different results from different issues. The solution was by analysing different existing detection methods in order to compare the dissimilar performance of existing processes. The precision of the system performance needs to be improved in order to invent a new method. As predicted from the result, the innovative construction method must be proposed and compared in order to find accurate, comprehensive measures and proper sampling procedures by the features of the selection method.     

Ventrolateral hypothalamic lesions in obese-hyperglycemic mice (obob)

Summary Bilateral electrolytic lesions were induced on the ventrolateral nucleus (VLN) of obese-hyperglycemic mice (obob) and lean littermates, with or without previous body weight reduction. All lean animals with VLN damage died within the first four post-operative days. In contrast, all obese mice (obob) with no prior body weight reduction recovered following an initial period of aphagia and rapid body weight loss. Three out of five reducedobob mice died following VLN lesions. - Two months after the operation the body weight of all lesionedobob mice stabilized at a level significantly lower than that of the sham operated obese; their serum immunoreactive insulin and blood glucose levels were also lower. - These data indicate thatobob mice respond normally to bilateral lesions of VLN and that their excess adiposity, by protecting them during the early post-operative period, facilitates their recovery. The final stabilization of the body weight of lesionedobob at a level lower than that of control mice is compatible with the view that the VLN acts as the low set point controller in the regulation of body weight.

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Ventrolaterale hypothalamische Läsionen bei obes- hyperglykämischen Mäusen (obob)

Zusammenfassung Bilaterale electrolytische Läsionen wurden in den ventrolateralen Kernen (VLN) von obeshyperglykämischen Mäusen (obob) und normalen Wurfgeschwistern mit oder ohne vorherige Gewichtsreduktion vorgenommen. Alle normalen Mäuse mit VLN-Läsionen starben innerhalb von vier Tagen nach der hypothalamischen Operation. Im Gegensatz dazu erholten sich alle fetten Mäuse (obob), deren Gewicht vor der hypothalamischen Operation nicht reduziert worden war, nach einer Periode von Aphagie und rapidem Gewichtsverlust. Drei von fünf gewichtsreduziertenobob-Mäusen starben nach der VLN-Operation. - Zwei Monate nach der Operation stabilisierten sich die Gewichte aller operiertenobob-Tiere auf einem statistisch signifikant niedrigeren Niveau, als dem der scheinoperierten fetten Mäuse entsprach. Immunoreaktives Insulin und Blutglucose waren bei diesen Tieren ebenfalls erniedrigt. - Die Ergebnisse deuten darauf hin, daßobob-Mäuse eine normale Reaktion auf die bilaterale Zerstörung der VLN zeigen und daß die überschüssige Fettmasse zu ihrer Erholung beitrug, indem sie ihnen in der Zeit unmittelbar nach der Operation Schutz gewährte. Die spätere Gewichtsstabilisation derobob auf einem subnormalen Niveau ist mit der gegenwärtigen Ansicht zu vereinbaren, daß die ventrolateralen hypothalamischen Kerne als die Regulatoren der unteren Körpergewichtsgrenze dienen.

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Lésions ventrolatérales de l'hypothalamus chez des souris obèses hyperglycémiques (obob)

Résumé Des lésions électrolytiques bilatérales du noyau ventrolateral (VLN) ont été pratiquées chez des souris obèses-hyperglycémiques (obob) et chez des souris de même portée non-obèses, avec ou sans réduction pondérale préalable. Tous les animaux maigres porteurs de lésions VLN décédèrent dans les quatre premiers jours post opératoires. Au contraire, toutes les souris obèses (obob) sans réduction pondérale préalable récupérèrent après une courte période d'aphagie et de perte de poids. Trois des cinq sourisobob préalablement soumises à un régime amaigrissant succombèrent après lésion du VLN. Deux mois après l'opération, le poids de tous lesobob porteurs de lésions du VLN atteignit un niveau stable mais significativement inférieur à celui des animaux soumis à une opération simulée. Il en fut de même du taux d'insuline immunoréactive et du glucose sanguin. -Ces résultats indiquent que la réponse desobob aux lésions bilatérales du VLN est normale et que leur excès de tissu adipeux les protège dans la période post opératoire et facilite leur récupération. La stabilisation du poids desobob à un niveau inférieur à la normale est compatible avec l'hypothèse que le VLN contrôle la limite inférieure du poids.

     

Past, present and future of A(2A) adenosine receptor antagonists in the therapy of Parkinson's disease

Several selective antagonists for adenosine A_2A receptors (A_2AR) are currently under evaluation in clinical trials (phases I to III) to treat Parkinson's disease, and they will probably soon reach the market. The usefulness of these antagonists has been deduced from studies demonstrating functional interactions between dopamine D₂ and adenosine A_2A receptors in the basal ganglia. At present it is believed that A_2AR antagonists can be used in combination with the dopamine precursor L-DOPA to minimize the motor symptoms of Parkinson's patients. However, a considerable body of data indicates that in addition to ameliorating motor symptoms, adenosine A_2AR antagonists may also prevent neurodegeneration. Despite these promising indications, one further issue must be considered in order to develop fully optimized antiparkinsonian drug therapy, namely the existence of (hetero)dimers/oligomers of G protein-coupled receptors, a topic that is currently the focus of intense debate within the scientific community. Dopamine D₂ receptors (D₂Rs) expressed in the striatum are known to form heteromers with A_2A adenosine receptors. Thus, the development of heteromer-specific A_2A receptor antagonists represents a promising strategy for the identification of more selective and safer drugs.     

食蟹猴纹状体18F-AV-133PET/CT的最佳显像时间和影像学特征

诊断帕金森病(Parkinson disease,PD)的方法较多,其中PET/CT功能显像方法在PD的早期诊断、鉴别诊断、病变严重程度分级及治疗效果的评价等方面都有重要价值[1]。本研究对正常食蟹猴、单侧及双侧纹状体损毁的PD模型食蟹猴进行18 F-AV-133PET/CT显像,研究大脑纹状体、额叶、颞叶、顶叶、枕叶、小脑、头皮、颅骨对18F-AV-133显像剂摄取的特征     

Maternally responsive neurons in the bed nucleus of the stria terminalis and medial preoptic area: Putative circuits for regulating anxiety and reward

Postpartum neuropsychiatric disorders are a major source of morbidity and mortality and affect at least 10% of childbearing women. Affective dysregulation within this context has been identified in association with changes in reproductive steroids. Steroids promote maternal actions and modulate affect, but can also destabilize mood in some but not all women. Potential brain regions that mediate these effects include the medial preoptic area (mPOA) and ventral bed nucleus of the stria terminalis (vBNST). Herein, we review the regulation of neural activity in the mPOA/vBNST by environmental and hormonal concomitants in puerperal females. Such activity may influence maternal anxiety and motivation and have significant implications for postpartum affective disorders. Future directions for research are also explored, including physiological circuit-level approaches to gain insight into the functional connectivity of hormone-responsive maternal circuits that modulate affect.     

Tumor necrosis factor‐α potentiates long‐term potentiation in the rat dentate gyrus after acute hypoxia

An inadequate supply of oxygen in the brain may lead to an inflammatory response through neuronal and glial cells that can result in neuronal damage. Tumor necrosis factor‐α (TNF‐α) is a proinflammatory cytokine that is released during acute hypoxia and can have neurotoxic or neuroprotective effects in the brain. Both TNF‐α and interleukin‐1β (IL‐1β) have been shown by a number of research groups to alter synaptic scaling and also to inhibit long‐term potentiation (LTP) in the hippocampus when induced by specific high‐frequency stimulation (HFS) protocols. This study examines the effects of TNF‐α on synaptic transmission and plasticity in hippocampal slices after acute hypoxia using two HFS protocols. Field excitatory postsynaptic potentials were elicited in the medial perforant pathway of the dentate gyrus. Exogenous TNF‐α (5 ng/ml) attenuated LTP induced by theta burst stimulation but had no effect on LTP induced by a more prolonged HFS. Pretreatment with lipopolysaccharide (100 ng/ml) or TNF‐α but not IL‐1β (4 ng/ml) prior to a 30‐min hypoxic insult resulted in a significant enhancement of LTP post hypoxia when induced by the HFS. Anti‐TNF, 3,6′‐dithiothalidomide (a TNF‐α synthesis inhibitor), and SB203580 (a p38 MAPK inhibitor) significantly reduced this effect. These results indicate an important modulatory role for elevated TNF‐α levels on LTP in the hippocampus after an acute hypoxic event. © 2015 Wiley Periodicals, Inc.     

Glial response in the rat models of functionally distinct cholinergic neuronal denervations

Alzheimer's disease (AD) involves selective loss of basal forebrain cholinergic neurons, particularly in the nucleus basalis (NB). Similarly, Parkinson's disease (PD) might involve the selective loss of pedunculopontine tegmental nucleus (PPT) cholinergic neurons. Therefore, lesions of these functionally distinct cholinergic centers in rats might serve as models of AD and PD cholinergic neuropathologies. Our previous articles described dissimilar sleep/wake‐state disorders in rat models of AD and PD cholinergic neuropathologies. This study further examines astroglial and microglial responses as underlying pathologies in these distinct sleep disorders. Unilateral lesions of the NB or the PPT were induced with rats under ketamine/diazepam anesthesia (50 mg/kg i.p.) by using stereotaxically guided microinfusion of the excitotoxin ibotenic acid (IBO). Twenty‐one days after the lesion, loss of cholinergic neurons was quantified by nicotinamide adenine dinucleotide phosphate‐diaphorase histochemistry, and the astroglial and microglial responses were quantified by glia fibrillary acidic protein/OX42 immunohistochemistry. This study demonstrates, for the first time, the anatomofunctionally related astroglial response following unilateral excitotoxic PPT cholinergic neuronal lesion. Whereas IBO NB and PPT lesions similarly enhanced local astroglial and microglial responses, astrogliosis in the PPT was followed by a remote astrogliosis within the ipslilateral NB. Conversely, there was no microglial response within the NB after PPT lesions. Our results reveal the rostrorostral PPT‐NB astrogliosis after denervation of cholinergic neurons in the PPT. This hierarchically and anatomofunctionally guided PPT‐NB astrogliosis emerged following cholinergic neuronal loss greater than 17% throughout the overall rostrocaudal PPT dimension. © 2014 Wiley Periodicals, Inc.