Rumex japonicus Houtt. Protects Dopaminergic Neurons by Regulating Mitochondrial Function and Gut–Brain Axis in In Vitro and In Vivo Models of Parkinson’s Disease

Parkinson’s disease (PD) is the second most common neurodegenerative disease worldwide. Rumex japonicus Houtt. (RJ) has been used to treat gastrointestinal and inflammatory diseases in East Asia. However, it is unknown whether RJ can prevent PD. We investigated the neuroprotective effects of RJ in cellular and animal PD models, focused on mitochondrial function and the gut–brain axis. SH-SY5Y cells were treated with RJ (0.01 mg/mL) for 24 h, after which they were treated with the 1-methyl-4-phenylpyridinium ion (MPP+). MPP+-induced apoptosis increased mitochondrial reactive oxygen species and decreased ATP, PINK1, and DJ-1, which were inhibited by RJ. Ten-week-old C57BL/6N male mice were treated with 30 mg/kg of 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) for 5 days and orally administered 50 or 100 mg/kg of RJ for 14 days. RJ alleviated MPTP-induced behavioral impairment, dopaminergic neuronal death, and mitochondrial dysfunction in the substantia nigra (SN) and suppressed the MPTP-induced increase in lipopolysaccharide, interleukin-1β, tumor necrosis factor-α, α-synuclein, and apoptotic factors in the SN and colon. Moreover, RJ inhibited the MPTP-mediated disruption of the tight junction barrier in the colon and blood–brain barrier of mice. Therefore, RJ alleviates MPTP-induced inflammation and dopaminergic neuronal death by maintaining mitochondrial function and tight junctions in the brain and colon.

Mild behavioral impairment: measurement and clinical correlates of a novel marker of preclinical Alzheimer’s disease

Background Late-life onset neuropsychiatric symptoms are established risk factors for dementia. The mild behavioral impairment (MBI) diagnostic framework was designed to standardize assessment to determine dementia risk better. In this Mini Review, we summarize the emerging clinical and biomarker evidence, which suggests that for some, MBI is a marker of preclinical Alzheimer’s disease. Main MBI is generally more common in those with greater cognitive impairment. In community and clinical samples, frequency is around 10–15%. Mounting evidence in cognitively normal samples links MBI symptoms with known AD biomarkers for amyloid, tau, and neurodegeneration, as well as AD risk genes. Clinical studies have found detectable differences in cognition associated with MBI in cognitively unimpaired people. Conclusion The emerging evidence from biomarker and clinical studies suggests MBI can be an early manifestation of underlying neurodegenerative disease. Future research must now further validate MBI to improve identification of those at the very earliest stages of disease.

The "disease of the crazy hatman" and the effects of human exposure to mercury: A case report / A "doença do homem do chapéu maluco" e os efeitos da exposição humana ao mercúrio: Um relato de caso

INTRODUCTION: Mercury, in addition to being a heavy metal, is considered a neurotoxin, that is, a substance capable of negatively affecting the neurological functions of the human body. Nowadays, ““Mad Hatter's Disease”” is the name used to characterize these neurological disorders caused by mercury. PURPOSE: to report a clinical case of the manifestation of “Mad Hatter's Disease”, as well as to discuss about the effects of human exposure to mercury. METHODOLOGY: this is a clinical case report, in which the patient is essential. CASE REPORT: A 45-year-old male patient, gold miner, from a riverside community in the Amazon, was referred to the hospital with complaints of headache, extremities tremor, diarrhea, tiredness, discouragement, irritability, depression, unusual shyness and hallucinations. On physical examination, the patient was anxious, irritable, symmetrical small-amplitude tremors in the extremities, hyperreflexia ++/4+ in the upper limbs, +/4+ in the lower limbs, normal muscle strength, mild ataxia of the right hand, stained skin and mucous membranes, and acyanotic, with erythematous-scaly lesions, confluent on the trunk, palms and soles of the feet. Screening for mercury poisoning was performed, where it was found, both in blood and urine, the presence of mercury 20 times above the biological tolerance limit. A battery of specific neuropsychological tests was carried out in neurotoxicological assessments and these demonstrated impairment of the cognitive domains (deficit of memory, attention, concentration, reasoning and abstraction) and alterations in motor functions, showing reduced coordination and motor speed. The diagnosis of hydrargyrism or occupational chronic metallic mercuralism (MMCO) was given. DISCUSSION: Chronic occupational exposure to inorganic mercury can cause subclinical abnormalities, as well as long-term psychomotor and neuromuscular behavioral impairment. Neuropsychiatric abnormalities (inattention, memory, interpretation, and motor performance) appear to be dose-related. FINAL CONSIDERATIONS: chronic exposure to metallic mercury vapor characteristically compromises the nervous system, initially with nonspecific symptoms and, later, with characteristic motor disorders - small amplitude tremor, paresis, dysreflexia and difficulty in motor coordination, which gives rise to the "Disease of the Mad Hatter”, and inhaling large amounts of mercury vapor can be lethal.

Neuropsychiatric Symptoms in Patients with Neurocognitive Disorder and Their Performance Between Mild and Major Stages

Background: The neuropsychiatric symptoms (NPS) in patients with neurocognitive disorders (NCD) increases the risk of exhibiting significant cognitive and functional decline. However, to the best of our knowledge, few studies have evaluated to what extent the presence of chronic and early NPS impacts cognition and functionality in patients with minor or major stages of NCD. Objective: We aimed to assess the interplay between early and chronic NPS and cognitive and functional presentation of patients with mild and major forms of NCD. Methods: We used two NPS tools tracking early and late NPS and assessed to what extent they determine cognitive and functional outcomes in patients with mild and major forms of NCD. Results: We found an inverse relationship between the presence of NPS, as measured by the Neuropsychiatric Inventory and Mild Behavioral Impairment Checklist (MBI-C), and cognitive and functional variables in major forms of NCD. In contrast, the minor stage of NCD was associated with increased MBI-C scores. Conclusion: Our results revealed that NPS are associated with cognitive and functional outcomes in mild and chronic forms of NCD. Crucially our results suggest that NPS could be considered as a pathological marker of the clinical course of dementia. Additionally, our study calls to study early and late forms of NPS as both impact cognition and functionality of NCD.

Pharmacological Actions of Myricetin in the Nervous System: A Comprehensive Review of Preclinical Studies in Animals and Cell Models

Myricetin is a natural flavonoid extracted from a variety of plants, such as medicinal herbs, vegetables, berries, and tea leaves. A growing body of evidence has reported that myricetin supplementation display therapeutic activities in a lot of nervous system disorders, such as cerebral ischemia, Alzheimer’s disease, Parkinson’s disease, epilepsy, and glioblastoma. Myricetin supplementation can also protect against pathological changes and behavioral impairment induced by multiple sclerosis and chronic stress. On the basis of these pharmacological actions, myricetin could be developed as a potential drug for the prevention and/or treatment of nervous system disorders. Mechanistic studies have shown that inhibition of oxidative stress, cellular apoptosis, and neuroinflammatory response are common mechanisms for the neuroprotective actions of myricetin. Other mechanisms, including the activation of the nuclear factor E2-related factor 2 (Nrf2), extracellular signal-regulated kinase 1/2 (ERK1/2), protein kinase B (Akt), cyclic adenosine monophosphate-response element binding protein (CREB), and brain-derived neurotrophic factor (BDNF) signaling, inhibition of intracellular Ca2+ increase, inhibition of c-Jun N-terminal kinase (JNK)-p38 activation, and suppression of mutant protein aggregation, may also mediate the neuroprotective effects of myricetin. Furthermore, myricetin treatment has been shown to promote the activation of the inhibitory neurons in the hypothalamic paraventricular nucleus, which subsequently produces anti-epilepsy effects. In this review, we make a comprehensive understanding about the pharmacological effects of myricetin in the nervous system, aiming to push the development of myricetin as a novel drug for the treatment of nervous system disorders.

Plasma Uric Acid Helps Predict Cognitive Impairment in Patients With Amyotrophic Lateral Sclerosis

Objective: Uric acid as an antioxidant plays an important role in neurodegenerative disease. Our objective is to investigate the relationship between plasma uric acid and cognitive impairment in patients with amyotrophic lateral sclerosis (ALS).Methods: In this cross-sectional study, 124 ALS patients were screened by the Edinburgh Cognitive and Behavioral Screen (ECAS) and classified according to the revised Strong's criteria. Additionally, based on total ECAS cut-off score patients were categorized into those with cognitive impairment (ALS-cie) and those without cognitive impairment (ALS-ncie), and clinical data and uric acid level were compared between the two groups. Parameters with significant differences were further included in a multivariate linear regression analysis with ECAS score as a dependent variable. Hold-out validation was performed to evaluate the fitness of regression model.Results: Up to 60% of ALS patients showed cognitive or/and behavioral impairment. The ALS-cie group had lower education level (p < 0.001), older age at symptom onset (p = 0.001), older age at testing (p = 0.001), and lower plasma uric acid (p = 0.01). Multivariate analysis showed increased uric acid (β = 0.214, p = 0.01), lower age at testing (β = −0.378, p < 0.001), and higher education level (β = 0.424, p < 0.001) could predict higher ECAS score (F = 19.104, R2 = 0.381, p < 0.0001). Validation analysis showed that predicted ECAS score was significantly correlated with raw ECAS score in both the training set (rs = 0.621, p < 0.001) and the testing set (rs = 0.666, p < 0.001).Conclusions: Cognitive impairment was a common feature in our Chinese ALS patients. Plasma uric acid might help evaluate the risk of cognitive impairment in ALS patients when combined with education level and age at testing.