Basic and Clinical Neuroscience最新文献

Introduction: Frontotemporal dementia (FTD) is a heterogeneous group of diseases with a complex clinical picture, including cognitive decline, behavioral and speech problems, psychiatric symptoms, and parkinsonism. Diagnosis of FTD is complex and requires the use of informative biomarkers.

Methods: We examined 226 Russian patients with FTD (mean age 69±10 years) and estimated the prevalence of the three most common genetic causes-mutations in the C9orf72, GRN, and MAPT genes. We also assessed the role of biochemical biomarkers, such as serum progranulin (PGRN) level and cerebrospinal fluid (CSF) levels of amyloid β (Aβ)-42 and phosphorylated tau protein (p-tau181).

Results: Mutations in C9orf72, GRN, and MAPT were present in 6%, 12.5%, and 2.5% of patients, respectively. The clinical phenotypes of these patients were described in detail. Low serum PGRN could be used to predict GRN-associated FTD cases. In most cases, we found normal CSF levels of Aβ-42 and p-tau181 except for 6, who had decreased Aβ-42 levels and normal p-tau181 levels.

Conclusion: We have conducted the first study of the genetic structure of FTD in Russia, the results of which, combined with other biomarkers, will help improve the diagnosis of the disease.

Introduction: Clean, noise-free data are ideal but often unattainable in biological control systems. Filters are usually employed to remove noise. But this process also leads to the loss or alteration of information. A considerable challenge is managing the uncertain knowledge using a proper and realistic mathematical representation and staying consistent with biological patterns and behaviors. This study explores the potential of fuzzy logic as a computational paradigm to manage uncertainties in the nonlinear dynamics of human walking. This field has paid little attention to this aspect despite its considerable nonlinear and uncertain behavior due to adaptability, muscle fatigue, environmental noise, and external disturbances.

Methods: We employed a fuzzy logic-based controller integrated with functional electrical stimulation (FES) and a gait basin of attraction concept to enhance gait performance. Our controller focused on accommodating imprecision in shank angle deviation and angular velocity rather than relying on predetermined trajectories.

Results: Our findings indicate that more fuzzy rules and partitions improve the similarity of the gait dynamics to those of a healthy human. Moreover, higher membership function overlaps lead to more robust gait control.

Conclusion: The study demonstrates that fuzzy logic can effectively manage uncertainties in the nonlinear dynamics of human walking, improving gait performance and robustness. This approach offers a promising direction for goal-oriented rehabilitation strategies by mimicking the human mind's ability to handle challenging and unknown environments.

Introduction: Partial peripheral nerve injury often results in chronic pain, including hyperalgesia and allodynia. Caffeine, as a non-selective antagonist of adenosine receptors (ARs), has protective effects on neuropathic pain. Since nitric oxide (NO) is partially involved in the central effects of caffeine, we investigated the effects of acute caffeine administration on neuropathic pain, focusing on A₁ and A₂ receptors and the possible role of NO.

Methods: Following chronic constriction injury (CCI), male Wistar rats were administered caffeine (10, 50, and 100 mg/kg). Also, groups of animals received L-NAME (30 mg/kg) or L-arginine (100 mg/kg) either alone or before treatment with 50 mg/kg of caffeine. Rats were tested for hyperalgesia and allodynia at 4, 7, 14, 21, and 28 days following CCI.

Results: Administration of 10 mg/kg of caffeine significantly increased cold allodynia, while 50 and 100 mg/kg of caffeine decreased mechanical allodynia and thermal hyperalgesia. Pre-treatment with L-NAME before caffeine administration decreased cold and mechanical allodynia and thermal hyperalgesia. Treatment with L-arginine before caffeine administration increased thermal hyperalgesia and decreased cold allodynia.

Conclusion: The present data show that caffeine dose-dependently affects the pro-analgesic or anti-analgesic states in the CCI model.

Introduction: The etiology of migraine is not fully understood, but there is ongoing debate about the potential role of immune dysfunction in migraine pathophysiology. Some clinical studies have shown a reduction in CD4⁺CD25⁺ regulatory T-cells (Treg) in migraine patients compared to healthy people. However, these studies have not been systematically analyzed. The primary objective of this study is to conduct a systematic review of Treg level changes in migraine patients.

Methods: A detailed literature search was conducted on PubMed, Scopus, Embase, ProQuest, Cochrane Review, Clinical trials, Academic thesis, American Academy of Neurology resources, and Google Scholar databases from 2010 to 2023. Studies that were appropriately designed to quantify Treg cell levels in migraine patients were included in this meta-analysis.

Results: Out of 17 studies initially reviewed, only 4 studies with 121 migraine patients were included for analysis. The meta-analysis revealed a statistically significant reduction in Treg cell levels in migraine patients compared to healthy volunteers (Z=1.21; P=0.23).

Conclusion: The observation of lower levels of Treg cells in migraine patients, compared to healthy volunteers, supports the theory that migraine may be an autoimmune disorder. However, additional clinical data is required to understand the role of immune dysregulation in migraine pathogenesis fully. This is the first meta-analysis of Treg cell levels in the context of migraine research, significantly contributing to the existing literature on the topic.

Introduction: The use of benzodiazepines and selective serotonin reuptake inhibitors to treat depression has severe adverse effects. This study aims to evaluate the effects of the methanolic leaf extract of Justicia secunda (MLEJS) on anxiety and depression in mice.

Methods: In this study, animals were male Swiss mice weighing 20-25 g. Gas chromatography-mass spectroscopy (GC-MS) phytochemical analysis of MLEJS was performed to verify the different bioactive components. An acute oral toxicity study was performed based on the Organization for Economic Co-operation and Development (OECD) guideline, No.423. We investigated the antidepressant and anxiolytic effect of MLEJS (12.5, 25, and 50 mg/kg) using lipopolysaccharide (LPS)-induced depression and flumazenil/benzodiazepine interaction in GABA (gamma-amino-butyric acid) receptors. The open field test, forced swimming test, and tail suspension test were performed to evaluate the depressive-like behavior in mice. Also, hole-board, light/dark box, elevated plus maze, thiopental sodium, and rotarod motor coordination tests were used as a screening paradigm for the anxiolytic effect of MLEJS.

Results: The MLEJS had an anxiolytic-like effect by increasing the exploration of the open arms and reducing the exploration of the closed arms in the elevated plus maze, light/dark box, and hole-board test. Moreover, LPS-induced depressive-like behavior in mice was reversed by the MLEJS (P<0.05). The significant attenuation of proinflammatory mediators and suppression of oxidative and nitrosative stress could be responsible for the observed effects (P<0.05).

Conclusion: The MLEJS can be an efficient therapeutic option against anxiety and depression concomitantly.

Introduction: Treatment of opioid use disorders (OUDs) via safe and effective approaches has been investigated for years. Methadone maintenance treatment (MMT) has been considered an effective therapy for opioid addiction. It has been observed that patients with genetic polymorphisms often show variability in the optimal drug dose requirement and treatment schedule. This study aimed to investigate the relationship between single nucleotide polymorphisms (SNPs) in the ATP-binding cassette subfamily B member-1 (ABCB1), the mu-opioid receptor (OPRM1), and cytochrome P450 (CYP) genes and methadone dose in patients undergoing MMT in Mazandaran Province, Iran.

Methods: In a cross-sectional study, 216 male MMT patients (20 to 45 years old) who were involved in the treatment program for at least three months were randomly recruited from six MMT clinics in Mazandaran province between 2018 and 2020. Blood samples were taken, DNA was extracted, and SNPs of CYP2B6 (G⁵¹⁶T, A⁷⁸⁵G), CYP2C19 (-3402C>T), CYP3A4 (-392A>G), OPRM (A¹¹⁸G), and ABCB1 (C³⁴³⁵T, G²⁶⁷⁷T, G²⁶⁷⁷A, and C¹²³⁶T) genes were evaluated using polymerase chain reaction-restriction fragment length polymorphism (RFLP).

Results: Our results showed no significant relationship between all the studied genotypes and methadone dose requirements.

Conclusion: The present study, for the first time in the Mazandaran population, reported no significant correlations between methadone dose requirement and different SNPs in the ABCB1, OPRM1, and CYP genes in MMT patients, which is consistent with other studies conducted on the Iranian population.

Introduction: Alzheimer disease (AD) is a progressive neurodegenerative disease that accounts for 60% of dementia cases worldwide. Despite the lack of concrete information about the prevalence of dysphagia among AD patients, it still significantly impairs their quality of life (QoL). That outcome necessitates more investigations to understand the pathophysiology of this condition and how to manage it. In this study, we examined if AD-associated changes in pharyngeal and tongue muscles could explain dysphagia.

Methods: Fourteen adult male rats were allocated into 2 groups: Group I (control) received distilled water orally, group II (AD) received aluminum chloride (AlCl₃) (200 mg/kg, per os) and D-galactose (60 mg/kg, subcutaneous) daily for 45 days. Biochemical parameters were conducted, including amyloid beta-peptide (Aβ), histopathological investigation of the hippocampus, tongue, and pharynx, and immune-histochemical expression of brain glial fibrillar acidic protein (GFAP).

Results: Our AD model showed marked cognitive impairment, hippocampal oxidative stress, and increased brain Aβ expression (P=0.0003) compared to controls. Dysphagia was confirmed by loss of body weight (P=0.0077) and decreased eating and drinking patterns by 25%-35% in AD versus the control group. Histopathological, immune-histochemical, and biochemical evidence, including increased levels of pharyngeal Aβ (P=0.0017), were detected in AD rats' tongue and pharyngeal muscles.

Conclusion: Dysphagia in AD can result not only centrally but also due to local involvement of the tongue and pharynx. Further translational studies linking dysphagia to AD pathology will be needed.

Introduction: Magnetic resonance imaging (MRI) is the preferred neuroradiologic tool for evaluating the sellar region. Pituitary adenomas account for about 15% of primary intracranial tumors. The optimal time for postoperative MRI of central nervous system neoplasms is 48 hours after surgery. Nevertheless, controversy exists regarding the timing of postoperative MRI in the sellar region. This study analyzed the sellar MRI findings of patients with pituitary adenoma at different times before and after surgery. Finally, we suggest the optimal time for postoperative sellar MRI imaging in patients with pituitary adenoma.

Methods: A total of 28 patients with pituitary adenoma were evaluated. All patients did four sellar MRIs. The first MRI was done before surgery, and three were done 48 hours, two weeks, and three months after the surgery. Finally, the MRI findings at different times were compared to each other.

Results: The pituitary gland and adenoma signals were constant at all time points. The signal of the packing material showed no differences in T1-weighted and T1-weighted with contrast sequences but showed changes in T2-weighted sequences.

Conclusion: Contrary to other intracranial neoplasms, there were no apparent changes in MRI signal intensity during the 3 months after surgery in patients with pituitary adenoma. There was also no superiority of one time point for performing follow-up imaging.

Introduction: In the present study, the culture of embryonic spinal motor neurons (SMNs) was used to assess the impacts of adrenomedullin (AM) on the neurotoxic effects of doxorubicin (DOX).

Methods: To prepare the culture of rat embryonic SMNs, spinal cords were isolated from the rat embryos, digested enzymatically, and triturated to obtain spinal cell suspension. Then, the SMNs were purified from the cell suspension using a single OptiPrep gradient and cultured. The SMNs were treated with DOX (0.0-100 μM) and AM (3.125-100 nM), and their viability and apoptosis were evaluated using MTT and annexin V flow cytometric assays. Oxidative stress was assessed through the measurement of cellular reactive oxygen species (ROS), nitric oxide (NO), malondialdehyde (MDA), and 8-iso-prostaglandin F2α (iPF2α) levels. Finally, qPCR was employed to determine the expressions of interleukin1-β (IL-1β), inducible NO synthase (iNOS), tumor necrosis factor-α (TNF-α), SRY-related protein 9 (SOX9), matrix metalloproteinase (MMP)-3 and -13.

Results: The viability of SMNs decreased following DOX treatment dose-dependently (IC₅₀=10.54 μM). DOX increased the cellular ROS, MDA, NO, and iPF2α levels (P<0.001). Additionally, AM reduced DOX-induced cell death dose-dependently (P<0.001). AM (50 nM) pretreatment also reduced the DOX-induced oxidative stress (P<0.01) and gene expression (P<0.01).

Conclusion: Based on the results, AM might be a protective factor against chemotherapy-induced toxicity in SMNs.

Introduction: It is common for individuals with internet addiction disorder (IAD) to demonstrate impairments in interference and inhibitory control. A primary objective of this study was to explore how interference control is related to event-related spectral perturbations (ERSPs) and whether participants with IAD experience changes in these spectral dynamics.

Methods: Twenty-one IAD participants and 20 healthy controls (HCs) were administered a Stroop task while their brains' electroencephalographic (EEG) activity was recorded. ERSPs were extracted from the EEG, and a cluster-based random permutation test was conducted to compare the power between the two groups at each time-frequency level.

Results: In the IAD group, the Stroop effect was significantly less for theta than in the HC group in an earlier time window. According to these results, IADs could not successfully inhibit their brain activation for stimulus conflict detection. Furthermore, IAD participants displayed a significant ERSP Stroop effect at beta2 and gamma frequencies, with the main contribution coming from bilateral dorsal frontal and parietal cortex over the scalp compared to HC participants.

Conclusion: In our study, IADs displayed reduced conflict detection and response selection compared to HCs, as measured by theta band indices, as well as impaired conflict resolution, as revealed by altered interaction dynamics between beta2 and gamma bands. Among the first studies investigating oscillatory dynamics in conflict resolution for IAD groups, this study uses cluster-based random permutation tests.