myelin-basic-protein and Cognitive-Dysfunction

Topics: Animals; Autoantibodies; Cognitive Dysfunction; Female; Humans; Immunoglobulin A; Immunotherapy; Mice; Mice, Knockout; Middle Aged; Multiple Sclerosis; Myelin Basic Protein; Myelin-Oligodendrocyte Glycoprotein; Rats

Vascular contributions to cognitive impairment and dementia (VCID) make up 50% of the cases of dementia. The purpose of this study was to determine the effect of chronic remote ischemic conditioning (C-RIC) on improving long-term (6 months) outcomes and cerebral blood flow (CBF) and collateral formation in a mouse model of VCID. Adult C57BL/6J male mice (10 weeks) were randomly assigned to four different groups: (1) sham-bilateral carotid artery stenosis (BCAS), (2) BCAS + sham RIC, (3) BCAS+C-RIC for 1 month (1MO), and (4) BCAS+C-RIC-4 months (4MO). CBF, cognitive impairment, and functional outcomes were performed up for 6 months after BCAS surgery. The expression of CD31, α-SMA, and myelin basic protein (MBP) was assessed by immunohistochemistry (IHC). Additional set of mice were randomized to sham, BCAS, and BCAS+C-RIC. The cerebrovascular angioarchitecture was studied with micro-CT. RIC therapy for either 1 or 4 months significantly improved CBF, new collateral formation, functional and cognitive outcomes, and prevented white matter damage. There was no difference between C-RIC for 1 or 4 months; IHC studies at 6 months showed an increase in brain CD31 and α-SMA expression indicating increased angiogenesis and MBP indicating preservation of white matter in animals receiving RIC. One month of daily RIC is as effective as 4 months of daily RIC in improving CBF, angiogenesis, and long-term functional outcomes (6 months) in a VCID model. This suggests that 1 month of RIC is sufficient to reduce cognitive impairment and induce beneficial cerebrovascular remodeling.

Topics: Actins; Angiography; Animals; Cerebrovascular Circulation; Cognitive Dysfunction; Cytokines; Dementia, Vascular; Disease Models, Animal; Gene Expression Regulation; Ischemic Preconditioning; Macrophages; Male; Maze Learning; Mice; Mice, Inbred C57BL; Myelin Basic Protein; Neovascularization, Pathologic; Nitrites; Random Allocation; Statistics, Nonparametric; Time Factors; Vascular Remodeling

Animal models of scopolamine-induced amnesia are widely used to study underlying mechanisms and treatment of cognitive impairment in neurodegenerative diseases such as Alzheimer's disease (AD). Previous studies have identified that melatonin improves cognitive dysfunction in animal models. In this study, using a mouse model of scopolamine-induced amnesia, we assessed spatial and short-term memory functions for 4 weeks, investigated the expression of myelin-basic protein (MBP) in the dentate gyrus, and examined whether melatonin and scopolamine cotreatment could keep cognitive function and MBP expression. In addition, to study functions of melatonin for keeping cognitive function and MBP expression, we examined expressions of brain-derived neurotrophic factor (BDNF) and tropomycin receptor kinase B (TrkB) in the mouse dentate gyrus. Scopolamine (1 mg/kg) and melatonin (10 mg/kg) were intraperitoneally treated for 2 and 4 weeks. Two and 4 weeks after scopolamine treatment, mice showed significant cognitive impairment; however, melatonin and scopolamine cotreatment recovered cognitive impairment. Two and 4 weeks of scopolamine treatment, the density of MBP immunoreactive myelinated nerve fibers was significantly decreased in the dentate gyrus; however, scopolamine and melatonin cotreatment significantly increased the scopolamine-induced reduction of MBP expression in the dentate gyrus. Furthermore, the cotreatment of scopolamine and melatonin significantly increased the scopolamine-induced decrease of BDNF and TrKB immunoreactivity in the dentate gyrus. Taken together, our results indicate that melatonin treatment exerts anti-amnesic effect and restores the scopolamine-induced reduction of MBP expression through increasing BDNF and TrkB expressions in the mouse dentate gyrus.

Topics: Animals; Antioxidants; Brain-Derived Neurotrophic Factor; Cognition; Cognitive Dysfunction; Demyelinating Diseases; Dentate Gyrus; Gene Expression Regulation; Male; Melatonin; Membrane Glycoproteins; Mice; Myelin Basic Protein; Receptor, trkB; Scopolamine; Signal Transduction

Exposures to toxic levels of vanadium and soluble vanadium compounds cause behavioral impairments and neurodegeneration via free radical production. Consequently, natural antioxidant sources have been explored for effective and cheap remedy following toxicity. Grewia carpinifolia has been shown to improve behavioral impairments in vanadium-induced neurotoxicity, however, the active compounds implicated remains unknown. Therefore, this study was conducted to investigate ameliorative effects of bioactive compounds from G. carpinifolia on memory and behavioral impairments in vanadium-induced neurotoxicity.. Sixty BALB/c mice were equally divided into five groups (A-E). A (control); administered distilled water, B (standard); administered α-tocopherol (500 mg/kg) every 72 hr orally with daily dose of sodium metavanadate (3 mg/kg) intraperitoneally, test groups C, and D; received single oral dose of 100 μg β-spinasterol or stigmasterol (bioactive compounds from G. carpinifolia), respectively, along with sodium metavanadate and the model group E, received sodium metavanadate only for seven consecutive days. Memory, locomotion and muscular strength were accessed using Morris water maze, Open field and hanging wire tests. In vivo antioxidant and neuroprotective activities were evaluated by measuring catalase, superoxide dismutase, MDA, H. In Morris water maze, stigmasterol significantly (p ≤ 0.05) decreased escape latency and increased swimming time in target quadrant (28.01 ± 0.02; 98.24 ± 17.38 s), respectively, better than α-tocopherol (52.43 ± 13.25; 80.32 ± 15.21) and β-spinasterol (42.09 ± 14.27; 70.91 ± 19.24) in sodium metavanadate-induced memory loss (112.31 ± 9.35; 42.35 ± 11.05). β-Spinasterol and stigmasterol significantly increased exploration and latency in open field and hanging wire tests respectively. Stigmasterol also increased activities of antioxidant enzymes, decreased oxidative stress markers and lipid peroxidation in mice hippocampal homogenates, and increased MBP expression.. The findings of this study indicate a potential for stigmasterol, a bioactive compound from G. carpinifolia in improving cognitive decline, motor coordination, and ameliorating oxidative stress in vanadium-induced neurotoxicity.

Topics: Animals; Antioxidants; Behavior, Animal; Cognitive Dysfunction; Down-Regulation; Hippocampus; Lipid Peroxidation; Male; Memory Disorders; Mice; Mice, Inbred BALB C; Myelin Basic Protein; Neurotoxicity Syndromes; Oxidative Stress; Stigmasterol; Vanadates

Rheumatoid arthritis (RA) has been associated with cognitive impairment and peripheral production of autoantibodies. Autoantibodies against central nervous system (CNS) proteins and S100 calcium-binding β (S100β) were found increased in diseases characterized by cognitive impairment like Alzheimer disease and Neuropsychiatric Systemic Lupus Erythematosus (NPSLE). The aim of this study was to investigate the plasma levels of autoantibodies against myelin basic protein (anti-MBP), myelin oligodendrocyte glycoprotein (anti-MOG) and S100β, and their relationships with cognitive performance in RA patients. Twenty patients with active rheumatoid arthritis and 19 age-, sex-, and schooling-matched healthy controls were recruited. Multiple dimensions of cognitive function were evaluated by structured clinical questionnaires. Autoantibodies and S100β levels were assessed by ELISAs. Patients had significantly higher levels of anti-MBP IgG (17.51 ± 1.36 vs. 5.24 ± 0.53 ng/mL), anti-MOG IgG (5.68 ± 1.34 vs. 0.51 ± 0.49 ng/mL), and S100β protein (2.24 ± 0.50 vs. 0.47 ± 0.06) than controls (all p < 0.0001). After adjusting for potential confounders, RA group presented worse cognitive performance involving the working memory and executive functions such as inhibition, flexibility, and mental control in parallel to higher autoantibodies and S100β levels than healthy controls (all p < 0.001). Levels of anti-MBP were negatively associated with delayed verbal recall (DVR; r = -0.42, p = 0.005), Stroop Color-Word (r = -0.48, p = 0.004), and N-Back Total scores (r = -0.59, p < 0.0001) and positively with Trail Making Test B (TMB, r = 0.53, p = 0.001). Negative correlation was found between levels of anti-MOG and DVR (r = -0.64, p < 0.0001), N-Back Total scores (r = -0.35, p = 0.03), Stroop Color-Word (r = -0.51, p = 0.001), and positively with TMB (r = 0.50, p = 0.003). S100β levels were associated with DVR (r = -0.51, p = 0.002), TMB (r = 0.46, p = 0.008), Stroop Color-Word (r = -0.67, p < 0.0001), and N-Back Total (r = -0.52, p = 0.003). RA is associated with impaired cognitive performance associated with higher levels of CNS-related autoantibodies and S100β levels. Given the importance of myelin integrity to cognition, our data indicate that these autoantibodies may be harmful to proper cognitive function.

Topics: Aged; Arthritis, Rheumatoid; Autoantibodies; Brazil; Case-Control Studies; Cognitive Dysfunction; Cross-Sectional Studies; Enzyme-Linked Immunosorbent Assay; Female; Humans; Linear Models; Male; Middle Aged; Multivariate Analysis; Myelin Basic Protein; Myelin-Oligodendrocyte Glycoprotein; S100 Calcium Binding Protein beta Subunit

To investigate the changes in serum neurological function parameters, interleukin (IL) and matrix metalloproteinase (MMP) in patients with cognitive dysfunction after single valve replacement.. 51 cases of senile patients with cognitive dysfunction after general anesthesia were selected as the observation group, and 51 senile patients without cognitive dysfunction after general anesthesia were selected as the control group. Serum neurological function parameters and IL and MMP levels were examined and compared between the two groups. The detected levels were also compared among patients with mild, moderate and severe cognitive dysfunction in the observation group. The relationship between these serum biomarkers and postoperative cognitive dysfunction was analyzed.. The serum neurological function parameters and IL and MMP levels were significantly higher in the observation group than those in the control group. Levels in the severe cognitive impairment group were higher than those in the mild and moderate groups, while those in the moderate group were higher than those in the mild group. Logistic analysis showed that the above indices were closely related to postoperative cognitive dysfunction in elderly patients with general anesthesia. The differences between the groups were statistically significant (p < 0.05).. Elderly patients with postoperative cognitive dysfunction after valve replacement surgery were presented with abnormalities in serum neurological function parameters and IL and MMP levels. There were significant differences in these indices between patients with varying degrees of cognitive dysfunction.

Topics: Aged; Aged, 80 and over; Anesthesia, General; Biomarkers; Case-Control Studies; Cognitive Dysfunction; Enzyme-Linked Immunosorbent Assay; Female; Heart Valves; Humans; Hydrogen Sulfide; Interleukins; Logistic Models; Male; Matrix Metalloproteinases; Middle Aged; Myelin Basic Protein; Phosphopyruvate Hydratase; Postoperative Complications

As the interest in the neuroprotective possibilities of docosahexaenoic acid (DHA) for brain injury has grown in the recent years, we aimed to investigate the long-term effects of this fatty acid in an experimental model of perinatal hypoxia-ischemia in rats. To this end, motor activity, aspects of learning, and memory function and anxiety, as well as corticofugal connections visualized by using tracer injections, were evaluated at adulthood. We found that in the hours immediately following the insult, DHA maintained mitochondrial inner membrane integrity and transmembrane potential, as well as the integrity of synaptic processes. Seven days later, morphological damage at the level of the middle hippocampus was reduced, since neurons and myelin were preserved and the astroglial reactive response and microglial activation were seen to be diminished. At adulthood, the behavioral tests revealed that treated animals presented better long-term working memory and less anxiety than non-treated hypoxic-ischemic animals, while no difference was found in the spontaneous locomotor activity. Interestingly, hypoxic-ischemic injury caused alterations in the anterograde corticofugal neuronal connections which were not so evident in rats treated with DHA. Thus, our results indicate that DHA treatment can lead to long-lasting neuroprotective effects in this experimental model of neonatal hypoxia-ischemic brain injury, not only by mitigating axonal changes but also by enhancing cognitive performance at adulthood.

Topics: Animals; Animals, Newborn; Axons; Behavior, Animal; Brain; Cognitive Dysfunction; Docosahexaenoic Acids; Glial Fibrillary Acidic Protein; Gliosis; Hippocampus; Hypoxia-Ischemia, Brain; Membrane Potential, Mitochondrial; Microglia; Mitochondria; Motor Activity; Myelin Basic Protein; Rats, Sprague-Dawley; Spatial Memory

Chronic cerebral hypoperfusion is a model for white matter lesions (WMLs) and cognitive impairment. In this study, we used the model in testing the protective effect of (-)-(2R)-1-[（4-β-D-glucopyranosyloxy)benzyl]-4-[4-(β-D-glucopyranosyloxy)benzyl]-2-isobutyl malate (militarine) on the white matter damaged. The model was established by bilateral common carotid ligation. Militarine (10 and 20 mg·kg(-1)·d(-1)) or saline was intragastrically administered daily for 30 days following the operation. Militarine (20 mg·kg-1·d-1)-treated rats exhibited significantly shorter escape latency, latency of the first time crossing and more numbers of platform crossings in Morris water maze task. Luxol fast blue (LFB) staining and Western blot analysis indicated that militarine promoted rehabilitation of white matter and increased levels of myelin basic protein (MBP) in the rats. Immunohistochemical staining for 2’,3’-cyclic-nucleotide 3’-phosphodiesterase (CNPase) revealed that militarine (20 mg·kg(-1)·d(-1)) markedly suppressed loss of CNPase-positive oligodendrocytes in the rat model. In conclusion, militarine can improve WMLs and cognitive impairment in the rat chronic hypoperfusion model.

Topics: 2',3'-Cyclic-Nucleotide Phosphodiesterases; Animals; Brain Ischemia; Cognitive Dysfunction; Disease Models, Animal; Maze Learning; Myelin Basic Protein; Rats; Succinates; White Matter

Myelin plays an important role in learning and memory, and degradation of myelin is a key feature in the pathogenesis of neurological disorders involving cognitive dysfunction. Myelin basic protein (MBP) is one of the most abundant structural proteins in myelin and is essential for myelin formation and compaction. In this study, we first examined changes in the distribution of MBP-immunoreactive myelinated fibers and MBP levels according to hippocampal subregion in mice following chronic systemic treatment with 1 mg/kg scopolamine (SCO) for 4 weeks. We found that SCO-induced cognitive impairments, as assayed by the water maze and passive avoidance tests, were significantly reduced 1 week after SCO treatment and the impairments were maintained without any hippocampal neuronal loss. MBP-immunoreactive myelinated fibers were easily detected in the stratum radiatum and lacunosum-moleculare of the hippocampus proper (CA1-3 region) and in the molecular and polymorphic layers of the dentate gyrus. The distribution of MBP-immunoreactive myelinated fibers was not altered 1 week after SCO treatment. However, the density of MBP-immunoreactive myelinated fibers was significantly decreased 2 weeks after SCO treatment; thereafter, the density gradually, though not significantly, decreased with time. In addition, the changing pattern of MBP levels in the hippocampus following SCO treatment corresponded to immunohistochemical changes. In brief, this study shows that chronic systemic treatment with SCO induced significant degradation of MBP in the hippocampus without neuronal loss at least 2 weeks after SCO treatment, although cognitive impairments occurred 1 week after SCO treatment.

Topics: Animals; Cognitive Dysfunction; Hippocampus; Male; Mice; Mice, Inbred ICR; Muscarinic Antagonists; Myelin Basic Protein; Neurons; Scopolamine