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体积 1, 问题 3 (2013)

评论文章

Possible Contribution of Microglial Glutamate Receptors to Inflammatory Response upon Neurodegenerative Diseases

Mami Noda and Kaoru Beppu

Microglial cells actively contribute to tripartite synapses by direct contact or releasing diffusible factors. In neuronmicroglia interaction, there are number of candidates as microglial signalling to neurons, for example neurotrophic factors, pro-inflammatory cytokines and chemokines. However, little is known about neuronal signalling to microglia. Microglial cells express various kinds of neurotransmitter receptors including glutamate receptors; both ionotropic and metabotropic glutamate receptors. Among them, microglial AMPA receptors are impermeable to Ca2+ due to the expression of GluA2. GluA2 is an important subunit in determining the functional properties of AMPA receptors, such as Ca2+ -permeability, conductance, assembly and trafficking. Activation of microglia induces membrane translocation of GluA2, while internalization of other subunits occurs, and nearly homomeric GluA2 subunits are suggested as the main reason for low conductance of AMPA receptors in activated microglia. Since low expression of GluA2 was reported in some neurodegenerative diseases, lack of GluA2 in microglia as well as in neurons contribute to excitotoxicity by excess release of proinflammatory cytokines such as TNF-α. Therefore, involvement of microglia in glutamatergic synaptic transmission may be also important to understand the mechanism of some neurodegeneration in which low GluA2 is suggested.

案例报告

Fahr’s Disease: A Rare Neurological Disease Frequently Misdiagnosed as Acute Psychosis, or Mood Disorder.

Suneel Kumar, Khalid Sher, Saeed Ahmed, Savita Naik, Shahana Ayub, Fatima B Motiwala and Rizwan Ahmed

Fahr’s disease is a rare, degenerative neurological disorder characterized by idiopathic symmetrical and bilateral intracranial calcification. We present a case of 32 years old man with Fahr’s disease who presented with episodes of inappropriate excessive laughing, generalized tonic clonic seizures associated with loss of consciousness, frothing from mouth, urine incontinence and difficulty in walking due to neurological deficit. MRI of brain demonstrated calcification of bilateral basal ganglia, thalami and left dentate nucleus of left cerebellum. The clinical presentation similar to our patient is frequently misdiagnosed due to identical manifestation to other neurological and psychiatric disorders especially in young to middle aged individuals. Fahr’s disease may often misdiagnosed as a patient of acute psychosis or epileptic seizures.

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Conotoxins: Possible Therapeutic Measure for Huntingtons Disease

Pallavi Bhosle and Sawarkar Vaibhav

Huntington’s disease (HD) is a genetic disorder with autosomal dominant inheritance with progressive degeneration of neurons. It is characterized by affective, cognitive, behavioral, and motor dysfunctions. 3 nitropropionic acid is well established animal model which initiates a complex series of neurochemical and signaling changes that lead to pathological events including neuronal excitotoxicity by excessive glutamate release, neuroinflammation and energy impairment. Excitotoxins like NMDA and kainic acid which binds to these receptors to release high levels of glutamate that can cause excitotoxicity by allowing high levels of calcium ions (Ca2+) to enter the cell. Ca2+ influx into cells activates a number of enzymes, including phospholipases, endonucleases, and proteases such as calpain. These enzymes increase apoptosis, oxidative stress and energy impairment thereby causing mitochondrial dysfunctions and go on to damage neuronal structures. The toxic venom used by the cone shells called conotoxin contains up to 50 different peptides that selectively inhibit the function of ion channels and excitatory amino acid receptors such as NMDA involved in the transmission of nerve signals in animals representing an extensive array of ion channel blockers each showing a high degree of selectivity for particular types of channels. Conotoxins selectively target a range of ion channels and NMDA receptors, making them widely useful tool for probing nervous system function. Here we hypothize the protective effect of conotoxins, from genus Conus geographus named w-conotoxin and conantoxin, against excitotoxic neuronal cell death using 3 NP induced Huntington’s model.

研究文章

Blocking Nogo Receptor 1 Promotes Functional Regeneration after Spinal Cord Injury

Mario Mezler, Moeller A, Mueller BK, Meyer AH, Schmidt MK, Ghayur T, Barlow E, Labkovsky B, Devanarayan V, Norreel JC and Mueller R

An insult to the mammalian spinal cord often results in persistent functional deficits. Proteins in CNS myelin are important determinants of this situation as they inhibit neurite growth. Among those proteins Nogo-A, oligodendrocyte myelin glycoprotein (OMgp), and myelin-associated glycoprotein (MAG) all bind to the neuronal Nogo-66 receptor (NgR1) and thereby block neuronal regeneration after injury. Neutralizing the interaction between the inhibitory ligands and NgR1 may alleviate the inhibition and therefore result in increased recovery after injury. Thus, antibodies neutralizing ligand/receptor interaction might have therapeutic value.

From a set of 300 monoclonal anti-NgR1 antibodies one anti-NgR1 ligand blocking antibody (mAb50) was selected for in vivo studies. mAb50 binds with high affinity (below 100 pM) to human and rat NgR1, competes for binding of a ligand peptide (derived from Nogo-A: Nogo66) to the isolated NgR1 protein and cellular NgR1, and reduces the inhibitory effects of Nogo66 on neurite outgrowth in differentiated human NTera2 cells and rat dorsal root ganglion neurons. In a rat spinal cord hemisection model mAb50 enhanced functional locomotor recovery. These data suggest that neutralization of NgR1 activity with an antibody may be a valuable strategy to neutralize neurite outgrowth inhibition in the mammalian CNS. Thus anti-NgR1 antibodies are a potential approach for the treatment of spinal cord injury and even neurodegenerative diseases.

研究文章

Experimental Study on the Connection of Nigral Apoptosis of Normal Rats and Rats of Parkinson Disease with Different Doses of Levodopa

Cao Fei, Sun Sheng-Gang, Cao Xue-Bing, Wang Tao, Cheng Ji-Xiang, Mei Yuan-Wu, Tong E-Tang and Luo Fang

Objective: To evaluate the neuronal toxicical effects induced by levodopa and explore the method in which PD can be treated reasonably with levodopa.
Method: The rat models of Parkinson disease (PD) were made by injecting stereotaxically 6-OHDA to right side of the mesencephic ventral tegmental area (VTA) and substantia nigra pars compacta (SNc). The PD rats were treated intraperitoneally with different dosages (10 mg/kg/d, 50 mg/kg/d, 100 mg/kg/d) and different durations (1 d, 3 d, 5 d, 7 d) of levodopa. At the same time, we observed the injury of substantia nigral by the way of treating PD rats with levodopa for 7 days and then stopped for 7 days. In this study, we used TUNEL to detect the injury of substantia nigra by different doses and durations of levodopa.
Results: The number of substantia nigral apoptosis was increased with the changes of doses and durations of levodopa.
Conclusions: If we use levodopa intermittently or as little as possible, the toxical action of levodopa may be reduced.

研究文章

Experimental Study on Parkinson Disease Model of Rats

Cao Fei, Sun Sheng-Gang, Cao Xue-Bing, Wang Tao, Cheng Ji-Xiang, Mei Yuan-Wu, Tong E-Tang and Luo Fang

Objective: To observe the characteristics of praxiology of Parkinson disease (PD) rats. Methods: At 1d, 7d, 14d after PD rats’ model were successful; we observed the markers of rotational behavior of Parkinson disease (PD) rats. For example: start time, continuous time, maximum turning, etc.
Results: From 1d to 14d, PD rats, start time of the rotational behavior elongated gradually, continuous time shortened by degrees, maximum rotational speed and the number of the rotational behavior were invariable.
Conclusions: Improved method of PD is scientific, reliable, and simple. Substantial nigral pathology of PD rats makes the foundation of the rotational behavior. The injury of substantial nigral can be reflected by maximum rotational speed and the number of the rotational behavior of PD rats.

研究文章

Experimental Study on the Neuronal Toxical Effect of Levodopa and the Inhibition of Ginkgo Biloba Extract on Parkinson Disease in Rats

Cao Fei, Sun Sheng-Gang and Tong E-Tang

Objective: To observe neuronal toxical effect of Levodopa and investigate whether using Levodopa together with EGb is an ideal, workable method to treat Parkinson disease.
Methods: In this study, the rat models of Parkinson disease (PD) were made by injecting stereotaxically 6-OHDA to right side of the mesencephic ventral tegmental area (VTA) and substantia nigra pars compacta (SNc). We used rotational behaviour, TUNEL, immunocytochemical, Nissl’s body staining methods to observe the difference between Levodopa (50mg/kg/d×3d, ×5d, ×7d, L-dopa group) and the combination use of Levodopa and EGb (100 mg/kg/d, E-D group).
Results: The numbers of apoptosis and rotation, bFGF protein expression in the L-dopa group surpassed those in the E-D group (P<0.05). The number of Nissl cells in the L-dopa group was fewer than the E-D group.
Conclusion: Levodopa has neurological toxical effect. EGb may decrease the toxicity of levodopa. The combination use of Ginkgo biloba extract (EGb) and Levodopa is a workable method to treat Parkinson disease and is better than using Levodopa alone.

研究文章

Using Real Time PCR For The Etiological Diagnosis Of Viral Encephalitis

Carlos J Rubinstein

Viral infections of the central nervous system (CNS) represent a challenge for early diagnosis and proper treatment of the disease. Different studies should be performed on the patient in order to arrive at an accurate diagnosis. The electroencephalogram, magnetic resonance imaging, viral culture, serological and cytochemical analysis are important tools to diagnose this disease. However, the polymerase chain reaction (PCR) or conventional PCR has become the gold standard for the diagnosis of viral encephalitis. Indeed, Real Time PCR (RT-PCR) equipments are replacing the conventional PCR ones. Faster results may be an explanation of this fact.
Information obtained from dissociation curve analysis of the RT-PCR technique represents a highly sensitive and specific tool for the Herpes simplex (HSV), Varicela (VZV), Cytomegalovirus (CMV) and Enterovirus (EV) detection.

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