Basic and Clinical Neuroscience
Year:2015 | Volume:6 | Issue:1|Papers Count:9

In the past few years, in vitro and in vivo genetic manipulations and ultimately effective functional alterations of a gene product have achieved a turning point. Here, I briefly summarize this exciting news for scientists, clinicians and patients.

Introduction: Diabetes mellitus is associated with nervous system alterations in both human and animal models. This study was done to determine the effect of gestational diabetes on the Purkinje and granular cells in the cerebellum of rat offspring.Methods: 10 Wistar rats Dams were randomly allocated in control and diabetic group. The experimental group received 40 mg/kg/body weight of streptozotocin (STZ) at the first day of gestation and control groups received saline injection intraperitoneally (IP). Six male offsprings of gestational diabetic mothers and control dams, at the 21, 28 postnatal days were randomly scarified and coronal sections of cerebellum (6 micrometer) serially collected. The neurons were stained with cresyl violet.Results: The Purkinje cells density in the apex and depth of cerebellum in P21, in the experimental group was reduced 23% and 15% in comparison with the control group (P<0.001). The granular cells density in the experimental group was reduced 19.58% and 18.3% in comparison with the controls (P<0.001). The Purkinje cells density of cerebellum in P28, in the diabetic group reduced to 22.12% and 12.62% in comparison with the control group (P<0.001). The granular cells density in the diabetic group reduced 17.14% and 16.12% in comparison with the control group (P<0.001).Discussion: The Purkinje and granular cells significantly reduced in gestational diabetes rat offspring.

Introduction: The basic objective of this study is to investigate the effects of alpha and theta brain waves amplitude increase in occipital area on reducing the severity of symptoms of generalized anxiety disorder and to increase the global functioning level in patients with GAD.Methods: This study is a quasi-experimental study with pre-test and post-test with two groups.For this purpose, 28 patients who had been referred to Sohrawardi psychiatric and clinical psychology center in Zanjan were studied based on the interview with the psychiatrist, clinical psychologist and using clinical diagnostic criteria for the Diagnostic and Statistical Manual of Mental Disorders text revision - the DSM-IV-TR Fourth Edition diagnosis of GAD, 14 subjects were studied in neurofeedback treatment group and 14 subjects in the waiting list group. Patients in both groups were evaluated at pre-test and post-test with General Anxiety Disorder Scale (GAD-7) and Global Assessment Functioning Scale (GAFs). The treatment group received fifteen 30-minute alpha training sessions and fifteen 30-minute theta brain training sessions in occipital area by neurofeedback training (treatment group). This evaluation was performed according to the treatment protocol to increase the alpha and theta waves. And no intervention was done in the waiting list group. But due to ethical issues after the completion of the study all the subjects in the waiting list group were treated.Results: The results showed that increase of alpha and theta brain waves amplitude in occipital area in people with GAD can increase the global functioning level and can reduce symptoms of generalized anxiety disorder in a treatment group, but no such change was observed in the waiting list group.Discussion: Increase of alpha and theta brain waves amplitude in occipital area can be useful in the treatment of people with GAD.

Introduction: Methadone has been used as a drug to detoxify opioid tolerance. Naloxane precipitated morphine withdrawal behaviours were attenuated by venlafaxine as an antidepressant.On the contrary, after detoxifying the opioids, spontaneous withdrawal syndrome may occur with pain sensitivity. Therefore the present study aimed to examine the effects of chronic methadone (70 mg/kg, in drinking water, 7 days), venlafaxine (80 mg/kg/day, intraperitoneally, 7 days) and their combinations with the spontaneous morphine withdrawal syndrome and pain sensitivity.Methods: Twenty eight young male Sprague-Dawley rats were randomly divided into 4 groups: control, venlafaxine treated, methadone treated and venlafaxine+methadone treated.Morphine sulfate (10 mg/kg/day, subcutaneously, 4 days) was injected to all animals. Then primary withdrawal behaviours and tail flick test were performed. The test was then followed by methadone or its vehicle administration. Second intervention was venlafaxine or its vehicle injection. Then final withdrawal behaviors and tail flick test were performed.Results: Combination of chronic methadone substitution and venlafaxine administration, significantly reduced freezing behavior of spontaneous morphine withdrawal syndrome (P<0.01, 379±144%). Chronic methadone administration (P<0.05, 35±8% difference with venlafaxine treated group) induced hyperalgesia. A positive correlation (P=0.001, +63%) was observed between the animals final freezing scores and their response latencies to the painful stimulus.Discussion: Combination of chronic methadone and venlafaxine administrations reduces freezing withdrawal behavior. Further investigations on analgesic interventions are needed to overcome this hyperalgesia.

Introduction: Diagnosing and treating diseases associated with amyloid fibers remain a great challenge despite of intensive research carried out. One important approach in the development of therapeutics is the use of herbal extracts which are rich in aromatic small molecules.Cinnamomum verum extract (CE) contains proanthocyanidin and cinnamaldehyde, which have been suggested to be capable of directly inhibiting amyloid fibril formation in vitro. This study is aimed at characterizing the inhibitory activity of CE against the fibrillation of hen egg white lysozyme (HEWL).Methods: Acidic pH and high temperatures were used to drive the protein towards amyloid formation. Lysozyme was dissolved at 2 mg/mL in 50mM glycine buffer (pH 2.5), and then incubated at 57oC for the specified durations while stirred gently by Teflon magnetic bars.Various techniques including thioflavin T, fluorescence, Congo red absorbance assay and AFM micrography were used to characterize the HEWL fibrillation processes.Results: In the absence of CE typical amyloid fibrils (like amyloids formed in Alzheimer disease) became evident after 48 h of incubation. Upon incubation with various extract concentrations in the range of 0.1-1 mg/ml, formation of fibrillar assemblies were significantly inhibited (P<0.05).AFM analysis and MTT assay also confirmed the role of the extract in amyloid inhibition. Our studies showed that the presence of CE did not have any effect on protein stabilization and thus directly interact with amyloid structure and inhibit formation of these structures. Furthermore, a docking experiment showed that a pi-pi interaction may occur between the aromatic component of cinnamaldehyde and W62. Interestingly, W62 is one of the principal aromatic residues that interact with glycine amide, which is an aggregation suppressor of HEWL.Discussion: These observations suggest that aromatic small molecules of CE may directly insert into amyloidogenic core of early aggregates and inhibit amyloid fibril formation by disrupting the pi-pi interactions.

Introduction: Group A Beta-Hemolytic Streptococcus (GABHS) can induce PANDAS (pediatric autoimmune neuropsychiatric disorders associated with streptococcal infection).GABHS is the most important and common bacterial cause of acute pharyngitis in Iranian children. We studied the role of GABHS (anti-streptococcal antibodies) in suspected cases of PANDAS in a cross sectional studies.Methods: Across sectional study was done in 2 pediatric psychiatric /and neurologic clinics in Tehran (Rasul Akram and Aliasghar Hospital) during 2008-2010. We studied serum antistreptococcal antibodies (anti streptolysin O, anti Deoxyribonuclease B, and anti-streptokinase (ABcam-ELISA, USA) in 76 cases with psychiatric manifestation (OCD, ADHD) in compare with 39 healthy controls. These antibodies were studied in 53 cases with movement disorders (Tic/ Tourette syndrome) in compare with 76 healthy controls. Sensitivity, specificity and positive predictive value of tests were calculated.Results: In movement disorders ASOT, Anti-DNase and Anti streptokinase was significantly higher than controls (P<0.0001, P=0.000, P<0.00001). ASOT (cut off level>200IU/ml) had 75% sensitivity; 84% specificity and 80% PPV; Anti- streptokinase (cut off level>332 IU/ml) had 34% sensitivity; 85% specificity, and 72% PPV; Anti-DNase (cut off level>140IU/ml) had 70% sensitivity; 99% specificity and PPV 90% for differentiating the group. ASOT, Anti-DNase and Anti streptokinase titer was significantly higher than controls (P<0.0001, P=0.000, P<0.0001).ASOT had 90% sensitivity; 82% specificity, PPV 92%; Anti streptokinase: 82% sensitivity; 82% specificity, PPV 95%; Anti DNase: 92% sensitivity; 82% specificity, PPV 92% for differentiation the cases from normal controls.Discussion: These findings support that a post infectious immune mechanism to GABHS may play a role in the pathogenesis of PANDAS in our children. A combination of throat culture, rapid antigen detection test, and serologic testing for GABHS is required to achieve maximum sensitivity and specificity for diagnosis. We prefer to use antibiotic prophylaxis in PANDAS cases for preventing recurrent streptococcal infections. Ongoing research is needed for identifying optimum diagnostic, prevention and therapeutic approach especially, aggressive treatment (intravenous immunoglobulin, plasmaphresis).

Introduction: Measuring the size of motor evoked potentials (MEPs) induced by transcranial magnetic stimulation (TMS) is an investigational technique to show the level of corticospinal excitability; however, some of the fundamental methodological aspects of TMS (such as the effects of inter-pulse intervals (IPI) on MEP size) are not fully understood, this issue raises concerns about the reliability of MEPs, especially in pre-test post-test studies.Methods: MEP size at short and long IPIs was assessed during two separate sessions. Inter- and intra-session reliability of MEP size also was assessed at both short and long IPIs.Results: The results indicated that long IPIs induced larger MEPs (P<0.05) across all time points.The intra-class correlation coefficient (ICC) indicated high intra- and inter-session reliability for short (0.87 to 0.96) and long (0.80 to 0.97) IPIs respectively. The amplitude of MEPs also had high intersession reliability for short (ICC=0.87) and long (ICC=0.80) IPIs.Discussion: This study provides evidence that the length of IPIs determines the size of MEPs. As a result, it is recommended to add the length of IPI to the international checklist of considerations for TMS application.

Introduction: Malignant astrocytic gliomas are the most common and lethal brain malignancies due to their refractory to the current therapies. Nowadays, molecular targeted therapy has attracted great attention in treatment of glioma. Connexin 43 (Cx43) and micro ribonucleic acid- 21 (miR-21) are among molecules that are involved in glioma development and progression.These molecules showed potential to be as target molecules with regard to glioma. Some studies have reported that cyclic adenosine monophosphate (cAMP) signaling could be effective on Cx43 and miR-21 in tissues other than in brain. We investigate possible relationship between b-adrenergic receptor and its newly described downstream, exchange protein directly activated by cAMP (Epac) signaling pathway and expression of Cx43 and miR-21 in low (1321N1) and high grade (U87MG) glioma cell lines.Methods: We treated cells with b-adrenergic agonist and Epac activator with and without adenyl cyclase inhibitor. Cx43 and miR-21 expression were measured with real-time PCR.Results: Our data showed that in 1321N1 cells, b-adrenergic-Epac pathway stimulation up and down-regulated Cx43 and miR-21 expression respectively. Whereas, in U87MG cells these interventions had no effect on Cx43 and miR-21 expression.Discussion: These findings demonstrate that low grade astrocytoma cells have better response to our pharmacological interventions.

Introduction: Prior studies comparing Hemodynamic Response Function (HRF) in the young and elderly adults based on fMRI data have reported inconsistent findings for brain vision and motor regions in healthy aging. It is shown that the averaging method employed in all previous works has caused this inconsistency. The averaging is so sensitive to outliers and noise. However, fMRI data are obscured with a major contribution of noise particularly in the elderly case.Methods: Deconvolution algorithm is here proposed for HRF extraction to achieve more robustness against noise. In spite of earlier works, proposed deconvolution algorithm yields compatible HRF results using either original or denoised fMRI data, though a large percentage of selected active voxels change in the latter case. In the current study, event-related fMRI data have been used for 18 subjects (8 young and 10 elderly adults) with a simple visual and motor task of pressing a key with index in response to the visual presentation of the word tap.Considering anatomically-defined vision and motor regions and preprocessing steps in FSL and SPM, the activated voxels have been selected according to t-test for which HRF is estimated using deconvolution method.Results: Experimental results demonstrate that HRF peak amplitudes do not differ significantly (P=0.8) in the vision region for the young and the elderly. In motor region, the HRF peak significantly increases for the young compared to the elderly (P<0.03). Repeating the procedure on the denoised fMRI data using MDL algorithm, the same results have been obtained.Discussion: In this study, a comparative study has been realized on the hemodynamic response properties associated with the young and the elderly adults on a simple visual and motor task.