Basic and Clinical Neuroscience
Volume:5 Issue: 1, Winter 2014

Depressive disorder is a prevalent psychiatric disorder، which affects 21% of the world population. The presently using drugs can impose a variety of side-effects including cardiac toxicity، hypopiesia، sexual dysfunction، body weight gain، and sleep disorder. During the last decade، there is a growing interest in the therapeutic effects of natural products on mental disorders. Amaranthus spinosus was investigation for antidepressant activity. Antidepressant activity of methanolic extract of Amaranthus spinosus (MEAS) was investigated by using Forced swimming test (FST) and Tail suspension test (TST) models. Escitalopram and Imipramine were used as reference standards. It has been observed from our study that both the MEAS at higher concentration showed significant (p<0. 01) reduction in immobility in tail suspension and forced swim model of depression comparable to Escitalopram and Imipramine. However further study is needed to understand mechanism of action and to identify active component responsible for antidepressant like activity.

Association between single-nucleotide polymorphisms (SNPs) in mu opioid receptor gene and drug addiction has been shown in various studies. Here, we have evaluated the existence of polymorphisms in exon 3 of this gene in Iranian population and investigated the possible association between these mutations and opioid addiction. 79 opioid-dependent subjects (55 males, 24 females) and 134 non-addict or control individuals (74 males, 60 females) participated in the study. Genomic DNA was extracted from volunteers’ peripheral blood and exon 3 of the mu opioid receptor gene was amplified by polymerase chain reaction (PCR) whose products were then sequenced. Three different heterozygote polymorphisms were observed in 3 male individuals: 759T>C and 877G>A mutations were found in 2 control volunteers and 1043G>C substitution was observed in an opioid-addicted subject. Association between genotype and opioid addiction for each mutation was not statistically significant. It seems that the sample size used in our study is not enough to confirm or reject any association between 759T>C, 877G>A and 1043G>C substitutions in exon 3 of the mu opioid receptor gene and opioid addiction susceptibility in Iranian population.

The objective of this study is development of driver’s sleepiness using Visually Evoked Potentials (VEP). VEP computed from EEG signals from the visual cortex. We use the Steady State VEPs (SSVEPs) that are one of the most important EEG signals used in human computer interface systems. SSVEP is a response to visual stimuli presented. We present a classification method to discriminate between closed eyes and opened eyes. Fourier transforms and power spectrum density features extracted from signals and Multilayer perceptron and radial basis function neural networks used for classification. The experimental results show an accuracy of 97% for test data.

Mild cognitive impairment can be considered as an intermediate clinical state between normal cognitive aging and mild dementia. Elderly people with this impairment represent an at-risk group for the development of dementia. The aim of this study was to investigate the prevalence of cognitive impairment in community-dwelling older adults by Mini-Mental State Examination (MMSE) and its relationship with socio-demographic variables. In this analytical-descriptive study, 212 subjects admitted to Hamadan’s day care centers were selected through simple random sampling method. To gather the data, MMSE was used as well as a questionnaire containing demographic variables. Data analysis was completed through SPSS-16. The sample consisted of 17.9% male, 59.4% of whom were married. According to the results, 96 cases (45.3%) suffered from mild (MMSE≥22), 110 cases (51.9%) from moderate (11≤MMSE≤21) and 6 cases (2.8%) from severe cognitive disorder (MMSE≤10). As findings revealed, factors such as age (Pv = 0.005, r = -0.491) and schooling (Pv < 0.001) are of significant relationship with MMSE score. Prevalence of cognitive decline in community-dwelling older adults was of normal range. Hence, familial relations and social support can decrease mental status disorder.

Inflammatory pain is a common sign of chronic diseases. Some brain regions such as locus coeruleus (LC) of the brainstem nor-epinephrine (NE) system have a key role in The mechanisms of the pain modulation and dependence. Bupropion synthesized as an antidepressant, but it is using for smoke cessation. It can change morphine withdrawal signs such as pain related behaviors. This study tested the acute effect of intra-LC microinfusion of bupropion on the formalin-induced pain behavior in rats. Wistar male rats were divided into 6 groups (control-naïve, control-operated, shamoperated, and 3 treated groups with 10-2, 10-3, 10-4 mol/μl intra-LC of bupropion). The injection guide cannulae were implanted into LC nuclei bilaterally by stereotaxic coordinated surgery under sterile condition. The sham group received normal saline as drug vehicle but control groups had no intra-LC injections. Formalin (50 μl, 2.5%) was injected subcutaneously in plantar region of the right hindpaw in all animals (30 min after drug administration in treated animals). Nociceptive signs were observed continuously and registered on-line each minute. Common pain scoring was used for pain assessment. The analysis of data by one-way ANOVA showed that bupropion can reduce pain behavior scores significantly. Bupropion reduced total pain score in the phase 01 (60%) and phase 02 (52%) of maximal behavior compared to the sham group, dose dependently and significantly. The pain scores of controls and sham groups had no significant difference. The results showed that bupropion has analgesic effects on LC neurons and can alter the neurochemical involvement of LC in pain process. Bupropion has different and significant effect on early and late phases of formalin test.

Combined use of an opioid with a psychostimulant is popular among drug abusers. Such “polydrug use” may increase drug effects or attenuate adverse effects of either drug alone. We proposed that a combination of methamphetamine (meth) and morphine may change physical opioid withdrawal symptoms. Adult male rats were chronically injected with cumulative subcutaneous (s.c.) doses of morphine, meth or a combination of both drugs within five days. On day six, a challenge dose of the same drug was injected. Two hours later, precipitated withdrawal symptoms were scored within 30 minutes after naloxone (1mg/kg, i.p.) injection. Both frequency and incidence of jumping significantly increased in combined treated animals (P<0.05). The sole emergent symptom in combined treated animals was digging which we consider as another escaping behavior in addition to jumping. Our findings imply that combined use of meth and morphine may exacerbate averseness of morphine withdrawal which may cause more intense opioid dependence

Formalin injection induces nociceptive bahaviour in phase I and II, with a quiescent phase between them. While active inhibitory mechanisms are proposed to be responsible for initiation of interphase, the exact mechanisms which lead to termination of nociceptive response in phase II are not clear yet. Phase II is a consequence of peripheral and central sensitization processes, which can lead to termination of the noxious stimuli responses; 45-60 minutes after formalin injection via possible recruitment of active inhibitory mechanisms which we have investigated in this study. To test our hypothesis, in the first set of experiments, we evaluated nociceptive response after two consecutive injection of formalin (50μL, 2%), with intervals of 5 or 60 minutes. In the next set, formalin tests were carried out in companion with injection of Naloxone Hydrochloride, a non-selective antagonist of opioid receptors, pre-formalin injection and 30 and 45 minutes post formalin injection. While normal nociceptive behaviour was observed in the group receiving one injection of formalin, a diminished response was observed in phases I and II of those receiving consequent injection of formalin, 60 minute after first injection. While second injection of formalin, 5 minute after first injection, had no effect. Administration of naloxone (1mg/kg) decreased nociception in phase 2A; but had no effect on delayed termination of formalin test. The results of this study suggest the existence of an active inhibitory mechanism, other than the endogenous opioids, that is responsible for termination of nociceptive behaviour at the end of formalin test.

Recent studies in affective computing are focused on sensing human cognitive context using biosignals. In this study, electrooculography (EOG) was utilized to investigate memory recall accessibility via eye movement patterns. 12 subjects were participated in our experiment wherein pictures from four categories were presented. Each category contained nine pictures of which three were presented twice and the rest were presented once only. Each picture presentation took five seconds with an adjoining three seconds interval. Similarly, this task was performed with new pictures together with related sounds. The task was free viewing and participants were not informed about the task’s purpose. Using pattern recognition techniques, participants’ EOG signals in response to repeated and non-repeated pictures were classified for with and without sound stages. The method was validated with eight different participants. Recognition rate in “with sound” stage was significantly reduced as compared with “without sound” stage. The result demonstrated that the familiarity of visual-auditory stimuli can be detected from EOG signals and the auditory input potentially improves the visual recall process.

Epilepsy is a neural disorder in which abnormal plastic changes during short and long term periods lead to increased excitability of brain tissue. Kindling is an animal model of epileptogenesis which results in changes of synaptic plasticity due to repetitive electrical or chemical sub-convulsive stimulations of the brain. Lateral hypothalamus, as the main niche of orexin neurons with extensive projections, is involved in sleep and wakefulness and so it affects the excitability of the brain. Therefore, we investigated whether lateral hypothalamic area (LHA) inactivation or orexin-A receptor blocking could change convulsive behavior of acute and kindled PTZ treated animals and if glutamate has a role in this regard. Kindling was induced by 40 mg/kg PTZ, every 48 hours up to 13 injections to each rat. Three consecutive stages 4 or 5 of convulsive behavior were used to ensure kindling. Lidocaine was injected stereotaxically to inactivate LHA, unilaterally. SB334867 used for orexin receptor 1 (OX1R) blocking administered in CSF. We demonstrated that LHA inactivation prevented PTZ kindling and hence, excitability evolution. Hippocampal glutamate content was decreased due to LHA inactivation, OX1R antagonist infusion, lidocaine injection and kindled groups. In accordance, OX1R antagonist (SB334867) and lidocaine injection decreased PTZ single dose induced convulsive behavior. While orexin-A i.c.v. infusion increased hippocampal glutamate content, it did not change PTZ induced convulsive intensity. It is concluded that LHA inactivation prevented kindling development probably through orexin receptor antagonism. CSF orexin probably acts as an inhibitory step on convulsive intensity through another unknown process.

Recent studies have shown that astrocytes play major roles in normal and disease condition of the central nervous system including multiple sclerosis (MS). Molecular target therapy studies in MS have revealed that connexin-43 (Cx43) and Aquaporin-4 (AQP4) contents of astrocytes undergo expression alteration. Fluoxetine had some effects in MS patients unrelated to its known antidepressant effects. Some of fluoxetine effects were attributed to its capability of cAMP signaling pathway stimulation. This study aimed to investigate possible acute effects of fluoxetine on Cx43 and AQP4 expression in astrocyte. Astrocytoma cells were treated for 24 hours with fluoxetine (10 and 20 μg/ml) with or without adenyl cyclase (AC) and protein kinase A (PKA) inhibition. Cx43 expression at both mRNA and protein levels and AQP4 expression at mRNA level were evaluated. Acquired results showed that fluoxetine with and without AC and PKA inhibition resulted in Cx43 up-regulation both in mRNA and protein levels, whereas AQP4 expression have not changed. In conclusion, data showed that fluoxetine alone and in the absence of serotonin acutely up-regulated Cx43 expression in astrocytes that can be assumed in molecular target therapy of MS patients. It seems that cAMP involvement in fluoxetine effects need more researches.

Today Nano-medicine tries to produce new drugs to reduce the dosage and side effects of their conventional forms. According to the interaction between zinc and opioidergic system activity, this study has investigated the effect of new kind of zinc supplement, nano zinc oxide (nZnO), in compared to its conventional form (cZnO), in presence and absence of opioidergic system activity on acute pain. Adult male Wistar rats (weighting 200±20gr) divided into groups: control (receiving saline %0.9), nZnO (1, 5, 10, 20 mg/kg), cZnO (1, 5, 10, 20 mg/kg), naloxone 1mg/kg, morphine 6 mg/kg, and co- injected groups of morphine and/or naloxone with nZnO (5mg/kg) and/or cZnO 10 mg/kg. Hot plate assay was used to evaluation of nociception and post injected latencies were recorded every 30 min for 90 min after I.P. injections of drugs. In co-injected groups latency time recorded after 60 minutes. Data indicated that both of ZnO supplements reduced latency time in dose and time dependent on the effect of nZnO was higher than cZnO. Also these components could improve anti-nociception effect of morphine and naloxone could not change the effect of these supplements. It seems that nZnO has more efficacy than its conventional form to showing analgesic effect that probably is related to the physicochemical properties of nZnO. Also may be these supplements have interaction with opioideric system in body.

Astrocytes are the most abundant glial cell type. In addition to their neurological roles, astrocytes also have immune functions. They have been involved in antigen presentation in the central nervous system (CNS). Activated astrocytes express adhesion molecules, chemokines and release several inflammatory mediators, pro-inflammatory cytokines, neurotrophic and neuroprotective factors, thus these cells have a dual role within the CNS: neuroinflammation and repair processes. IL-19, IL-20, IL-22, IL-24, IL-26, IL-28A, IL-28B, and IL-29 are members of the IL-10 family of cytokines. These cytokines have different biological functions in spite of partial amino acid sequences homology. Signal transduction of the IL-10 family of cytokines is through R1-type and R2-type receptors. No information has been available about the expression and regulation of IL-19 in mice astrocytes and brain. To investigate the expression of IL-19, we examined its expression in C57BL/6 mice astroglial cells in response to lipopolysaccharide (LPS), using reversetranscription polymerase chain reaction (RT-PCR) method. We provide for the first time, evidence that astrocytes can express IL-19 mRNA following LPS stimulation. Furthermore, we have found the expression of IL-19 mRNA in the cortex of adult C57BL/6 mice following intraperitoneal (i.p.) administration of LPS. This finding will contribute to current knowledge on the function and behavior of cells and mediators during inflammatory conditions in the brain

In the 1960s, discovery of pleasure system (defined as reward system) in the brain that may underlie drug reward and addiction encouraged many scientists to investigate the mechanisms by which drug abuse affects central nervous system function. In this regard, investigators developed several drugs targeting the brain reward system for drug dependence therapy. However, no positive results obtained in drug addiction treatment. It seems that more brain systems other than brain reward system must be considered in this regard.