Basic and Clinical Neuroscience
Volume:10 Issue: 6, Nov-Dec 2019

In this Correspondence, a comment to a recent paper by Nikbakht et al., published in the latest ssu of this Journal is reported. The flavone apigenin can exert both its anti-oxidant potetial via the usual enzymatic ROS scavenging system and the mitochondria biogenesis via the PGC-1α/ TFAM/NRF-1 pathway. The very interesting paper by Nikbakht et al, may earn more insighful clues about the activity of apigenin in the prevention of the rat hippocampus neuronal loss caused by the Aβ25-35 injection.

Alzheimer disease (AD) is a neurodegenerative disorder characterized by the progressive loss of memory and other cognitive functions. Protein kinase Cε (PKCε) is an isoform that most effectively suppresses amyloid beta (Aβ) production and synaptic loss.

In this study, spatial learning and memory for treated rats were evaluated by the Morris water maze test. The activity (total PKC), mRNA expression, and protein level of PKCε in the platelet and hippocampal tissue were evaluated using immunosorbent assay, real-time qPCR, and western blotting analysis, respectively. 

The traveled distance was significantly prolonged, and escape latency significantly increased in Aβ-treated groups. PKC activity assay showed that there was a remarkable difference between the Aβ-treated and sham-operated groups on days 10 and 30 in the hippocampus and also day 30 in platelet after the injection of Aβ. A significant effect in PKC activity was observed between days 0 and 10, days 0 and 30, as well as days 5 and 30. Aβ significantly downregulated the PKCε mRNA expression in the hippocampus of rats on day 30; however, no significant difference was observed in platelet. Western blot analysis demonstrated that Aβ significantly reduced PKCε protein expression in the hippocampus of treated groups on day 30. 

The expression level of PKCε was downregulated following the injection of Aβ in the hippocampus, but no significant difference was observed between the AD and sham groups in platelet that may be due to the low concentration of PKCε or duration of Aβ exposure in the rat brain.

Cognitive dysfunction is the most common problem of patients with Alzheimer disease (AD). The pathological mechanism of cognitive impairment in AD may contribute to neuronal loss, synaptic dysfunction, and alteration in neurotransmitters receptors. Mitochondrial synapses dysfunction due to the accumulation of amyloid beta (Aβ) is one of the earliest pathological features of AD. The flavone apigenin has been reported to play some protective roles in AD through the anti-oxidative and anti-inflammatory properties. This study aimed at investigating the effects of apigenin on spatial working memory and neural protection by restoring mitochondrial dysfunction and inhibition of caspase 9.

Intracerebroventricular (ICV) microinjection of Aβ 25-35 was used for AD modeling. Working memory was assessed 21 days later using the Y maze test. Neuronal loss was detected in the hilar area of the hippocampus using Nissl and Fluoro-jade B staining, whereas immunohistochemistry was used to illustrate cytochrome c positive cells and caspase 9.

The results revealed that apigenin significantly ameliorated spatial working memory. It also significantly reduced the number of degenerative neurons in the hilus area. Apigenin almost completely blocked the release of cytochrome c and caspase 9 in hilus.

Apigenin may improve the spatial working memory deficits and neuronal degeneration through the amelioration of the mitochondrial dysfunction.

Trimethyltin Chloride (TMT) is a neurotoxin that can kill neurons in the nervous system and activate astrocytes. This neurotoxin mainly damages the hippocampal neurons. After TMT injection, behavioral changes such as aggression and hyperactivity have been reported in animals along with impaired spatial and learning memory. Hence, TMT is a suitable tool for an experimental model of neurodegeneration. The present study aims to determine the palliative effects of Bone Marrow-derived Mesenchymal Stem Cells (BM-MSCs) on the hippocampi of rats damaged from TMT exposure.

We assigned 28 male Wistar rats to the following groups: control, model, vehicle, and treatment. The groups received Intraperitoneal (IP) injections of 8 mg/kg TMT. After one week, stem cells were stereotactically injected into the CA1 of the right rats’ hippocampi. Spatial memory was determined by the Morris Water Maze (MWM) test 6 weeks after cell transplantation. Finally, the rats’ brains were perfused and stained by cresyl violet to determine the numbers of cells in the Cornus Ammonis (CA1) section of the hippocampus. We assessed the expressions of Glial Fibrillary Acidic Protein (GFAP) and Neuronal-specific Nuclear (NeuN) proteins in the right hippocampus by Western blot.

The MWM test showed that the treatment group had significantly higher traveled distances in the target quarter compared with the model and vehicle groups (P<0.05). Based on the result of cell count (Nissl staining), the number of cells increased in the treatment group compared with the model and vehicle groups (P<0.05). Western blot results showed up-regulation of GFAP and NeuN proteins in the model, vehicle, and treatment groups compared with the control group. 

Injection of BM-MSCs may lead to a behavioral and histological improvement in TMT-induced neurotoxicity by increasing the number of pyramidal neurons and improving memory.

Migraine is considered one of the most common primary headache disorders. Migraine attacks may occur due to a lack of sleep. Furthermore, sleep is regarded as one of the smoothing factors of migraine pain. Patients with sleep disorders often suffer from headaches when they wake up compared with healthy individuals. 

This research was a quasi-experimental study with a pretest-posttest design and a 2-month follow-up. The samples included 20 migraine patients within the age range of 15 to 55 years who were selected as volunteers for treatment by the neurologists and psychiatrists during 2017. The initial evaluation was then conducted based on the inclusion and exclusion criteria and using the Ahvaz migraine questionnaire, and Pittsburgh sleep quality index. The patients were randomly assigned to two neurofeedback (n=10) and transcranial direct current stimulation (tDCS) (n=10) groups and evaluated three times. The obtained data were analyzed by the repeated measures ANCOVA and Chi-square test in SPSS. 

Based on the scores of both groups, no significant difference was observed between neurofeedback and tDCS groups. However, based on the results, neurofeedback decreased sleep latency, whereas tDCS increased sleep efficiency. Overall, these two treatments were effective in improving subjective sleep quality and sleep quality.

Both neurofeedback and tDCS treatments could significantly enhance sleep quality of the patients in the posttest and 2-month follow-up. Given the effectiveness of both treatments, neurofeedback and tDCS are recommended to be used for improving the sleep status of patients with migraine.

Brain lateralization is associated with human behavior. Therefore, this study aimed at investigating the effects of brain lateralization on the scores of paranormal beliefs.

The study population included 180 students of Sanandaj universities, Sanandaj City, Iran who were selected with convenience sampling method (100 left-brained males, 6 left-brained females, 56 both left- and right-brained males and 22 both left- and right-brained females). The research tools were the paranormal belief scale developed by Blackmore (1994), as well as the brain lateralization questionnaire (1985). 

The obtained findings suggested a significant difference between the left-brain and right-brained people in terms of paranormal beliefs. A significant difference was also found between the left-brained males and both left- and right-brained females in terms of paranormal beliefs. 

The paranormal beliefs of the left-brained cases were different from both left- and right-brained subjects, which can be seen between the left-brained males and both left- and right-brained females.

Sensory Gating Inventory (SGI) measures behavioral aspects of Sensory Gating (SG), which filters irrelevant sensory inputs into the higher cortex. It modifies sensitivity to sensory stimuli. Abnormal SG leads to overloading of information in the brain and its subsequent dysfunction. Electrophysiological techniques cannot assess the behavioral aspects of SG. We aimed to design the Persian version of SGI with high validity and reliability.

After a forward and then backward translation of the original SGI, we assessed the content validity and construct validity of the Persian version. A total of 405 participants filled the Persian version of SGI. To assess test-retest reliability, 100 participants filled the inventory again 7-10 days later. The content validity ratio and index, as well as confirmatory factor analysis, were computed, too. Finally, the Cronbach’s alpha, Cohen’s kappa, and intraclass correlation coefficients were calculated. 

The content validity ratios of all items of the inventory were more than 60%, which means that they were necessary according to the experts’ opinions. Confirmatory factor analysis confirmed the fitness of the 4-factor structure of the original Inventory. The test-retest reliability using the intraclass correlation coefficient and Cronbach’s alpha coefficients were also high for the four subscales. The Cohen’s kappa coefficients revealed moderate to substantial level of agreement between the first and second scores for all items.

The Persian version of SGI has good and acceptable psychometric properties. It can be used as a valid and reliable tool for studying behavioral aspects of SG in Persian speaking population.

Cell therapy has been widely considered as a therapeutic approach for neurodegenerative diseases and nervous system damage. Cholinergic neurons as one of the most important neurons that play a significant role in controlling emotions, mobility, and autonomic systems. In this study, human dental pulp stem cells (hDPSCs) were differentiated into the cholinergic neurons by β-mercaptoethanol in the preinduction phase and also by the nerve growth factor (NGF) in the induction phase. 

The hDPSCs were evaluated for CD73, CD31, CD34, and Oct-4. Concentration-time relationships for NGF were assessed by evaluating the viability rate of cells and the immune response to nestin, neurofilament 160, microtubule-associated protein-2, and choline acetyltransferase.

The hDPSCs had a negative response to CD34 and CD31. The optimal dose for the NGF was 50 ng/mL seven days after the induction when the highest percentage of expressing markers for the cholinergic neurons (ChAT) was detected.

The results of this study provided a method for producing cholinergic neurons by hDPSCs, which can be used in cytotherapy for degenerative diseases of the nervous system and also spinal cord injury.

Parkinson disease (PD) is the second most common neurodegenerative disease affecting older individuals with signs of motor disability and cognitive impairment. Epicatechin (EC) and edaravone have neuroprotective effects most probably due to their antioxidant activity; however, a limited number of studies have considered their role in PD. This research aimed at investigating the neuroprotective effect of EC and edaravone in a neurotoxin-induced model of PD.

An in vitro model of PD was made by subjecting SH-SY5Y neuroblastoma cells to neurotoxin: 6-hydroxydopamine (6-OHDA) 100 µM/well. The cytoprotective effect of EC and edaravone in five concentrations on cell viability was tested using the MTT assay. The apoptotic assay was done by annexin V and propidium iodide method using flow cytometry.

According to the MTT assay analysis, EC and edaravone had protective effects against 6-OH DA-induced cytotoxicity in SH-SY5Y neuroblastoma cells that were much more significant for edaravone and also a relative synergistic effect between EC and edaravone was observed. The apoptotic analysis showed that edaravone alone could decrease early and late apoptosis, whereas EC diminished early apoptosis, but enhanced late apoptosis and necrosis. Besides, co-treatment of edaravone and EC had a synergistic effect on decreasing apoptosis and increasing cell viability. 

The protective effect of edaravone on apoptosis and cytotoxicity was demonstrated clearly and EC had a synergistic effect with edaravone.

The central-governor model explains the mechanism of endurance exercise-induced central fatigue, but high-intensity exercise-induced central fatigue has not been investigated yet. This study aimed to research how central fatigue during high-intensity intermittent pedaling alters the neural response, which results in electroencephalography (EEG) recordings.

We assessed neural response by measuring the alternation of brainwave spectral power during an intermittent high-intensity 60-minute exercise on an ergometer cycle. The cadences were changed every 10 minutes according to intermittent pattern altering (90-120-60-120-60-90 rpm). EEG was used to analyze altering brain function. Heart rate (HR), blood lactate (BL), and rating of perceived exertion (RPE) were measured after the change in cadences.

HR, BL, and RPE increased at a cadence of 120 rpm compared with 60 rpm on the ergometer cycle. The spectral power of EEG, according to cadence × brainwaves, significantly increased (P˂0.01) in the alpha and beta frequency ranges with a change in cadences between 60 rpm and 120 rpm. The spectral power of the EEG significantly increased (P˂0.01) over the whole frequency range from rest to warming (theta: 251%, alpha: 165%, beta: 145%) and significantly reduced in theta, alpha, and beta (theta: 176%, alpha: 142%, beta: 77%) (P≤0.01).

High-intensity exercises (90 and 120 cadences) increased brain function, regardless of fatigue occurrence. High-intensity interval training (HIIT) led to altering the neural response. It would be required to investigate the usefulness of HIIT to treat some of the psychotic disorders.

Addiction to opioids is a serious problem and concern in any nation today.  Unfortunately, the rate of taking these drugs and addiction to them has drastically increased. This research aimed at the study of the degree of the BDNF serum level, reducing depression, stress and also studied the diminishing the craving by means of transcranial direct current stimulation (tDCS) in opioid abusing patients.

The research method was a quasi-experimental design with a pre-post test administered on three groups. The statistical population included all addicted people to opioids in Zanjan. A sample of 30 patients was selected based on the DSM-5 diagnosing criteria through available sampling and then they were randomly placed into three groups of 10 people. After all the participants knowingly filled out the consent forms before performing an intervention, they were evaluated by ELISA technique to measure the serum level of BDNF, then a desires for drugs questionnaire (DDQ), depression, anxiety and stress scale (DASS) were administered. Then, for 10 sessions of 20 minutes, tDCS for the three groups, namely Group A (L-DLPFC) anodal left/catodal right, group B( R-DLPFC) anodal right/cathodal left, and group C (sham-tDCS) were administered. After the treatment, all the participants were reevaluated and then the data were analyzed by Kolmogorov- Smirnov test, one-way analysis of variance (ANOVA) and the Bonfreoni test.

The results showed that stimulating the DLPFC led to a significant change in growing the level of BDNF (P= .031) and lowering the degree of depression (p= .018), anxiety (p= .001), stress (p= .012) and decreased the level of craving (p= .001) in opioid addicted patients. Moreover, the pair comparison indicated that group B showed a significant improvement versus group C.

The findings of this research suggest that TDCS is an effective and a complementary treatment, beside the common treatments of opioid abusing patients.