Changes in the Expression of Genes of the Glutamate Transporter and Subunits of the NMDA and AMPA Receptors in the Rat Amygdala in the Lithium–Pilocarpine Model of Epilepsy

The molecular changes in the glutamatergic system of the rat amygdala were studied during the latent phase of the lithium–pilocarpine model of temporal lobe epilepsy in order to identify the potential involvement of these changes in epileptogenesis. The real-time PCR method was used to evaluate the mRNA expression of the NMDA and AMPA receptor subunits, as well as the excitatory amino acid transporter-2 (EAAT2) in the basolateral nucleus of the amygdala 7 days after the seizures caused by administration of pilocarpine. The results of the experiments were as follows: (1) an increase in the expression ratio of the GluN2a/GluN2b NMDA receptor subunits with an unchanged expression level of the GluN1 subunit; (2) increased expression of the GluA2 subunit of AMPA receptors with the invariance of GluA1, and (3) enhanced expression of the EAAT2. According to literature data, the expression of the same genes decreased in the hippocampus in the same model of epilepsy. Neurodegeneration was reported in both brain regions. The opposite changes in the expression of the glutamatergic system genes in the hippocampus and amygdala during the latent period of the lithium–pilocarpine model suggest the occurrence of factors that can both contribute to and hinder epileptogenesis.     

Injury of mitochondria and the expressions of fas and bax mRNA in the hippocampus of epileptic rats of different latency

IN T R O D U C T IO N M itochondria provide cells energy through oxidative phosphorylation by m eans of ATP. Biochem icalevidence indicates that m ost ATP consum ptions in brain are used forthe electric activity ofneurons, so the sufficientenergy supply f…     

Challenges in the diagnosis and treatment of transsexualism in contemporary China

##正##According to the International Classification of Diseases10th Edition(ICD-10),[1]transsexualism refers to thecondition where an individual desires to live and to beaccepted as someone of the gender which is oppositetheir biological sex.It is usually accompanied withdiscomfort or distress about their anatomic sex.In somecases,individuals with this condition modify their bodyfeatures using laser or plastic surgeries to resemble     

Emotion and Theory of Mind in Schizophrenia—Investigating the Role of the Cerebellum

Social cognitive dysfunction, including deficits in facial emotion recognition and theory of mind, is a core feature of schizophrenia and more strongly predicts functional outcome than neurocognition alone. Although traditionally considered to play an important role in motor coordination, the cerebellum has been suggested to play a role in emotion processing and theory of mind, and also shows structural and functional abnormalities in schizophrenia. The aim of this systematic review was to investigate the specific role of the cerebellum in emotion and theory of mind deficits in schizophrenia using previously published functional neuroimaging studies. PubMed and PsycINFO were used to search for all functional neuroimaging studies reporting altered cerebellum activity in schizophrenia patients during emotion processing or theory of mind tasks, published until December 2014. Overall, 14 functional neuroimaging studies were retrieved. Most emotion studies reported lower cerebellum activity in schizophrenia patients relative to healthy controls. In contrast, the theory of mind studies reported mixed findings. Altered activity was observed across several posterior cerebellar regions involved in emotion and cognition. Weaker cerebellum activity in schizophrenia patients relative to healthy controls during emotion processing may contribute to blunted affect and reduced ability to recognise emotion in others. This research could be expanded by examining the relationship between cerebellum function, symptomatology and behaviour, and examining cerebellum functional connectivity in patients during emotion and theory of mind tasks.     

What is the role of the hippocampus and parahippocampal gyrus in the persistence of tinnitus?

The hippocampus and parahippocampal gyrus have been implicated as part of a tinnitus network by a number of studies. These structures are usually considered in the context of a “limbic system,” a concept typically invoked to explain the emotional response to tinnitus. Despite this common framing, it is not apparent from current literature that this is necessarily the main functional role of these structures in persistent tinnitus. Here, we highlight a different role that encompasses their most commonly implicated functional position within the brain—that is, as a memory system. We consider tinnitus as an auditory object that is held in memory, which may be made persistent by associated activity from the hippocampus and parahippocampal gyrus. Evidence from animal and human studies implicating these structures in tinnitus is reviewed and used as an anchor for this hypothesis. We highlight the potential for the hippocampus/parahippocampal gyrus to facilitate maintenance of the memory of the tinnitus percept via communication with auditory cortex, rather than (or in addition to) mediating emotional responses to this percept.     

Modeling the Protonation States of the Catalytic Aspartates in β-Secretase and the Process of the Enzymatic Hydrolysis

背景：阿尔茨海默病(AD）主要表现为脑内β-淀粉样蛋白（Aβ）沉积，Aβ由β-淀粉酶（β- Secretase，BACE）催化水解淀粉样前体蛋白（amyloid precursor protein, APP）产生，但是BACE的催化机制至今仍不清楚。 目的：确定质子在BACE催化性氨基酸(Asp 32 和 Asp 228)中的精确定位，同时在计算机上模拟BACE催化底物APP蛋白的全部过程，揭示BACE催化水解底物的机制。 设计，时间和 SETTING: 全部的量子化学计算在中山大学中山医学院人体解剖教研室进行，2008年8月至2009年3月。 材料: 一台linux计算机工作站，商业性的大型药物设计软件包Schrodinger, 针对学术机构免费的量子化学软件 MOPAC 2007。 方法: 在计算机上构建了一个BACE催化模型，应用量子化学/分子力学(QM/MM)相结合的方法在密度泛函理论水平的基础上计算质子在BACE催化性氨基酸(Asp 32 和 Asp 228)中的精确定位； 在量子化学的半经验理论水平基础上模拟BACE催化水解底物肽EVNL/AAEF的全部过程。 主要结果指标: 计算BACE和底物在不同的单质子化状态下两个催化性氨基酸中的4个羧基氧原子的共面性；在模拟催化水解底物过程中检测BACE催化活性区域内空间和能量的变化。 结果： BACE的同分异构体228o,其4个催化氨基酸羧基氧原子形成的二面角为8.7°；而且利用这种同分异构体（228o）作为初始状态，催化水解底物的活化能最低（1.6959 kcal/mol），焓最高（-7.4055 kcal/mol）。 结论：在催化前，质子最有可能位于BACE的催化氨基酸Asp 228的外位羧基氧原子上,催化水解时，Asp 228作为催化酸，Asp 32 作为催化碱驱动催化水分子攻击底物，形成四面体中间物后，质子的换位到Asp 32的内位羧基氧原子上。     

Effects of apomorphine and β-carbolines on firing rate of neurons in the ventral pallidum in the rats

The ventral pallidum (VP) is a critical element of the mesocorticolimbic system that is inter-connected with motor and limbic structures and may be considered as an interface between motivational and effector neural signals. Dopamine is important in behavioral output of the VP, and dysfunctioning its dopamine quantity leads to various neuropsychiatric disorders. Understanding neural substrate underlying this phenomenon has become an important affair in recent years. In this study, neuronal activities were recorded from the VP in presence or absence of the mixed dopamine D1/D2 receptor agonist, apomorphine, and/or β-carbolines, using an extracellular single-unit recording technique. We reported that subcutaneous administration of apomorphine (0.5 mg/kg) decreased neural activity in the VP. In addition, neither harmine (7.8 mg/kg; i.p.) nor harmane (4 mg/kg; i.p.) and norharmane (2.5 mg/kg; i.p.) had any effect on neural firing in the VP. Finally, pretreatment with β-carbolines prevented the apomorphine-induced inhibition on VP firing rate. Thus, according to the results of aforementioned study and our results in the present study, we can conclude that presumably most responses in the VP are D2 dopamine dependent. Although the β-carbolines were unable to alter neural activity in the VP, interestingly, pretreatment with β-carbolines protect decreasing in firing rate of neurons in the VP followed by apomorphine administration. This protective effect could be explained by interaction between β-carbolines and dopaminergic mechanisms.     

Preliminary investigations on melatonin and 5-methoxytryptophol synthesis in the pineal,retina, and Harderian gland of the mole rat and in the pineal of the mouse “eyeless”

Summary Hydroxyindole-O-methyltransferase (HIOMT) activity for the synthesis of melatonin and 5-methoxytryptophol, both 5-methoxyindoles, was measured in the pineal, the Harderian gland and the retina of the mole rat and in the pineal of the mouse eyeless. In the pineal and the Harderian gland of the mole rat a larger amount of 5-methoxytryptophol than of melatonin is synthesized. 5-Methoxyindole synthesis is extremely high in the Harderian gland, whereas in the retina HIOMT activity is low and variable. In the pineal of the mouse eyeless, a low 5-methoxyindole synthesis showing no circadian rhythm is demonstrated. It is concluded that, besides the generally accepted regulation of the indole metabolism by light, in species with atrophied eyes having Harderian glands (mole rat) and in species without eyes other factors than light might be responsible for the indole metabolism in the pineal gland.     

Can people remain engaged and vigorous in the face of trauma? Palestinians in the West Bank and Gaza

This is the first study to investigate how actively engaged and vigorous people remain in their life tasks in the midst of chronic exposure to significant traumatic events. We sought to identify risk and protective factors for engagement within the context of ongoing exposure to political violence and social upheaval. We randomly identified and interviewed 1,196 adult residents of the West Bank and Gaza during a period of violent conflict on 3 occasions: (1) September-October 2007, (2) April-May 2008, and (3) October-November 2008. Participants were asked about their exposure to political violence, symptoms of depression, and posttraumatic stress (PTS) symptoms, their level of social support, psychosocial resource loss, and positive engagement in life tasks. Path modeling revealed that trauma exposure indirectly affected engagement through its impact on resource loss and PTS and depression symptoms. PTS symptoms at Wave 2 were modestly related to greater engagement at Wave 3, and depression symptoms did not independently predict engagement at Wave 3. Psychosocial resource loss at Wave 1 and Wave 2 was the best overall predictor of engagement at Wave 3, through its direct and indirect effects via PTS symptoms. Greater engagement was also predicted by greater social support, being more educated, being younger, and being more religious. The relative independence of psychological distress and engagement was noted as a critical finding supporting a key tenet of positive psychology. The relationship of resource loss and social support with engagement suggests that bolstering psychosocial resources may offer a route for primary and secondary prevention amidst chronic traumatic conditions.     

Alteration of orexin-A and PKCα in the postmortem brain of pure-opioid and multi-drug abusers

Finding changes induced by the drug of abuse is one of the most important approaches to design new drugs for the treatment of substance use disorders (SUD). Postmortem study is the most reliable method for detecting alteration in the brain of SUD patients. Recently, the role of orexinergic system in SUD is in consideration. In the current study, we evaluated the level of orexin-A in the CSF and protein kinase Cα (PKCα) in the brain of pure-opioid (POA) and multi-drug abusers (MDA).A total of 56 POA, 45 MDA, and 13 matched control brains were collected from the legal medicine center, Tehran, Iran. The CSF was gathered from the third ventricle immediately after opening the skull and kept at −80 °C. The medial prefrontal cortex (mPFC), lateral prefrontal cortex (lPFC), orbitofrontal cortex (OFC), nucleus accumbens (NAc), and amygdala were dissected from fresh brain, frozen with liquid nitrogen and kept at −80 °C. The level of orexin-A evaluated in the CSF. Using western blotting, the level of PKCα assessed in the brain.Obtained data revealed that the level of orexin-A increased in POA and MDA compared with the control group (p < 0.05). In addition, the level of PKCα increased in the prefrontal cortex and amygdala of the abusers compared with the control group, although we did not detect changes in the level of PKCα in the NAc.Along with animal studies, the current results showed that the level of orexin increased in the CSF of drug abusers, which might be related to increases in the activation of lateral hypothalamic orexinergic neurons faced with the drug of abuse. Enhancement in the level of PKCα in the drug reward circuits might be adaptational changes induced by orexin and drugs of abuse.     

Prevalence and costs of headaches for the public health system in a town in the interior of the state of São Paulo

Despite the high prevalence, impact and economic importance of headaches, studies on this subject are rare in Brazil. The aim of the present study was to estimate the prevalence of headaches in the public health system of a town in the interior of the State of S?o Paulo, as well as to estimate the costs resulting from its management. Data refer to the year of 1998 and were obtained according to the following steps: 1) territorial and demographic characterization of the municipality; 2) characterization of the financial indices and social well-being; 3) budget characteristics of the municipality; 4) evaluation of the structuring of the medical service; 5) determination of the prevalence of headaches at different patient care levels; and 6) calculation of the costs of headaches. Headaches represented 7.9% of all visits at basic health units, 9.7% in the emergency room and 1.1% of hospital admissions. The total costs were R$ 85,131.31 (US$ 70,942.76) corresponding to R$ 7.59 (US$ 6,32) per inhabitant/year. The present study shows the need for epidemiological and economic impact studies, which would provide the basis for the rational use of health funds.     

Melatonin and the time window for the expression of the α8 nicotinic acetylcholine receptor in the membrane of chick retinal cells in culture

We have previously shown that melatonin influences the development of α8 nicotinic acetylcholine receptor (nAChR) by measurement of the acetylcholine-induced increase in the extracellular acidification rate (ECAR) in chick retinal cell cultures. Cellular differentiation that takes place between DIV (days in vitro) 4 and DIV 5 yields cells expressing α8 nAChR and results in a significant increase in the ECAR acetylcholine-induced. Blocking melatonin receptors with luzindole for 48 h suppresses the development of functional α8 nAChR. Here we investigated the time window for the effect of melatonin on retinal cell development in culture, and whether this effect was dependent on an increase in the expression of α8 nAChR. First, we confirmed that luzindole was inhibiting the effects of endogenous melatonin, since it increases 2-[¹²⁵I] iodomelatonin (23 pM) binding sites density in a time-dependent manner. Then we observed that acute (15, 60 min, or 12 h) luzindole treatment did not impair acetylcholine-induced increase in the ECAR mediated by activation of α8 nAChR at DIV 5, while chronic treatment (from DIV 3 or DIV 4 till DIV 5, or DIV 3.5 till DIV 4.5) led to a time-dependent reduction of the increase in the acetylcholine-induced ECAR. The binding parameters for [¹²⁵I]-α-bungarotoxin (10 nM) sites in membrane were unaffected by melatonin suppression that started at DIV 3. Thus, melatonin surges in the time window that occurs at the final stages of chick retinal cell differentiation in culture is essential for development of the cells expressing α8 nAChR subtype in full functional form.     

Distinct roles in vivo for the ubiquitin-proteasome system and the autophagy-lysosomal pathway in the degradation of α-synuclein

Increased intracellular levels of α-synuclein are implicated in Parkinson's disease and related disorders and may be caused by alterations in the ubiquitin-proteasome system (UPS) or the autophagy-lysosomal pathway (ALP). A critical question remains how α-synuclein is degraded by neurons in vivo. To address this, our study uses α-synuclein transgenic mice, expressing human α-synuclein or α-synuclein-eGFP under the (h)PDGF-β promoter, in combination with in vivo pharmacologic and multiphoton imaging strategies to systematically test degradation pathways in the living mouse brain. We demonstrate that the UPS is the main degradation pathway for α-synuclein under normal conditions in vivo while with increased α-synuclein burden the ALP is recruited. Moreover, we report alterations of the UPS in α-synuclein transgenic mice and age dependence to the role of the UPS in α-synuclein degradation. In addition, we provide evidence that the UPS and ALP might be functionally connected such that impairment of one can upregulate the other. These results provide a novel link between the UPS, the ALP, and α-synuclein pathology and may have important implications for future therapeutics targeting degradation pathways.     

Functions of the nigrostriatal dopaminergic synapse and the use of neurotransplantation in Parkinson’s disease

While pharmaceutical options remain the overwhelmingly accepted treatment of choice for neurological and psychiatric diseases, significant accomplishments in regenerative neuroscience research have demonstrated the potential of cellular and synaptic functional repair in future therapies. Parkinson’s disease stands out as an example in which repair by dopaminergic neurons appears a viable potential therapy. This article describes the basic neurobiological underpinnings of the rationale for cell therapy for Parkinson’s disease and the challenges ahead for the use of regenerative medicine in the treatment for this disease.     

Comparative microanatomy of the lateral wall of the ‘cavernous sinus’ in humans and the olive baboon

Abstract

Despite many studies of the ‘cavernous sinus’ lateral wall, the anatomy of this area remains controversial. We performed a comparative microanatomical and histoarchitectural study in 14 humans and in 10 nonhuman primates (Papio cynocephalus anubis). Venous channels and cranial nerves were embedded in the ‘interperiosteodural space’. The dura propria of the lateral wall could be removed without entering the venous compartment. The oculomotor and trochlear nerves were accompanIed by an arachnoidal and dural sheath. The oculomotor nerVe sheath stopped under the anterior clinoid process in baboons. The trigeminal ganglion was covered posteriorly with an arachnoid membrane and adhered firmly to the dura propria on lateral aOnd anterior sections. The three branches of the trigeminal nerve had no arachnoid covering, except for arachnoid granulations in humans. In baboons, the oculomotor and trochlear nerves were thicker than in humans, while the ophthalmic nerve was thinner. The abducens nerve belonged to the lateral wall of the sinus in baboons and had no arachnoidal sheath except in the first millimeters of Dorello’s canal. After leaving their arachnoidal and dural sheath, the intracavernous cranial nerves acquired a typical peripheral sheath. The venous channels in both species’ were true dural sinuses. Willis cords and adipose tissue were identified. [Neural Res 1997; 19: 571-576]