Metabolic brain disease最新文献

According to the Diagnostic and Statistical Manual of Mental Disorders, Fifth Edition, Autism Spectrum Disorder (ASD) is characterized by persistent difficulties in social communication and interaction, together with restricted and repetitive behaviors, interests, or activities. The diagnosis of ASD currently relies on comprehensive assessments of developmental history and behavioral patterns, as there are no validated laboratory tests for a definitive clinical diagnosis. While evidence-based interventions are largely restricted to educational and behavioral programs, many individuals with ASD and their caregivers explore complementary approaches, including dietary interventions. Among these, the gluten-free, casein-free (GFCF) diet is one of the most frequently adopted strategies. A leading hypothesis posits that those increased concentrations of opioid peptides such as gluteomorphin and caseomorphin derived from the incomplete digestion of gluten and casein may contribute to the severity of ASD symptoms. It is further suggested that eliminating these dietary proteins could reduce opioid peptide concentrations in biofluids and improve clinical outcomes. The present systematic review was created by reviewers who searched PubMed, Web of Science, and Scopus databases, covering the period from January 1980 to March 2025. The search strategy combined standardized keywords and Medical Subject Headings terms. The search strategy included a combination of keywords commonly used in the literature to represent ASD, opioid peptides, and GFCF diets. A systematic literature search was carried out on PubMed and Web of Science and a total of 17 articles were included. Although preliminary findings from clinical and laboratory studies are promising, conclusive evidence regarding the efficacy of the GFCF diet remains lacking. This review aims to synthesize current findings on the relationship between opioid peptides and ASD, with a particular focus on the neurological effects of food-derived peptides and their potential role in therapeutic dietary interventions.

Nitric oxide (NO) and reactive oxygen species (ROS) are central to the pathophysiology of cardiovascular and neurological disorders, influencing intricate signaling pathways that manage vascular function, inflammation, and oxidative stress. NO, predominantly produced by NO-synthases, plays a vital role in maintaining vascular health by facilitating vasodilation and preventing platelet aggregation. However, its reaction with superoxide results in the formation of peroxynitrite, a highly reactive molecule that intensifies oxidative damage and impairs endothelial function. Elevated ROS levels, arising from sources like NADPH oxidases and mitochondrial activity, further heighten oxidative stress, driving the progression of conditions like atherosclerosis and neurodegenerative diseases. Therapeutic strategies aimed at restoring the balance between NO and ROS include the use of antioxidants to neutralize ROS, pharmacological methods to enhance NO bioavailability, and nanoparticle-based systems designed to address oxidative stress. Emerging research points to potential of targeting redox-sensitive pathways, such as the Keap1-Nrf2 axis, to slow disease progression. In neurological disorders, overproduction of ROS leads to neuroinflammation and neuronal apoptosis, which are central to conditions like Alzheimer's and Parkinson's disease. This review explores the complex relationship between NO and ROS in disease mechanisms, emphasizing cutting-edge therapeutic strategies that utilize redox signaling in cardiovascular and neurological conditions.

Background: Depression is a common psychiatric disorder, with stress-induced neuroinflammation playing a crucial role in its pathogenesis. Acupuncture has been demonstrated to be both effective and safe in the treatment of depression, but its precise mechanisms remain unclear.

Method: This study investigated acupuncture's effects on neuroglia-associated neuroinflammation in chronic unpredictable mild stress (CUMS)-induced depressive rats. Rats underwent CUMS for 28 days, with the acupuncture group receiving treatment at Shangxing (GV23) and Fengfu (GV16) every other day. The fluoxetine group received daily intragastric fluoxetine. Depression-like behaviors were assessed through body weight measurements and behavioral tests. Hippocampal pathology was examined using hematoxylin and eosin (H&E) staining, and immunofluorescence was used to detect activated microglia in the hippocampus. Western blotting (WB) analyzed key proteins associated with microglial phenotypes, including CD16, inducible nitric oxide synthase (iNOS), CD206, and arginase-1 (Arg-1). Additionally, nuclear factor kappa B (NF-κB), NOD-like receptor protein 3 (NLRP3), apoptosis-associated speck-like protein containing a CARD (ASC), cysteine-aspartic acid protease-1 (caspase-1), and gasdermin D (GSDMD) levels were measured using WB and reverse transcription-polymerase chain reaction (RT-PCR). Cytokines interleukin-1β (IL-1β), interleukin-6 (IL-6), tumor necrosis factor-alpha (TNF-α), interleukin-10 (IL-10), and interleukin-4 (IL-4) were quantified via enzyme-linked immunosorbent assay (ELISA).

Result: Acupuncture significantly alleviated CUMS-induced depression-like behaviors, enhancing sucrose preference and reducing immobility time. It inhibited microglial M1 polarization, downregulated NF-κB and NLRP3 expression, and suppressed pyroptosis-related proteins like caspase-1 and GSDMD.

Conclusion: Acupuncture alleviates depression-like behaviors in CUMS-induced rats by modulating microglial polarization and inhibiting neuroinflammation-mediated pyroptosis. Our findings provide further evidence supporting acupuncture as a viable strategy for depression treatment.

This study aimed to evaluate the memory health benefits of Neurocaf™, a standardized green coffee bean extract. Neurocaf was characterized for the presence of 5-hydroxytryptamide esters, eicosanoyl-5-hydroxytryptamide (EHT), and chlorogenic acids using HPLC-PDA detector. The inhibitory kinetics of Neurocaf against acetylcholinesterase (AChE) were assessed in vitro. Cognitive efficacy was further investigated in a scopolamine-induced amnesia mouse model. In a 25-day study, male Swiss albino mice (25-30 g) were pretreated orally with Neurocaf (200 or 400 mg/kg body weight) or donepezil (3 mg/kg body weight) for 14 days followed by behavioural assessments and a 7-day co-treatment with scopolamine (0.75 mg/kg, i.p.). Neurocaf exhibited mixed competitive AChE inhibition in vitro (IC₅₀ = 298.4 µg/mL). At 400 mg/kg, it significantly enhanced spatial memory performance, demonstrated by reduced transfer latency in the elevated plus maze (p < 0.01) and decreased escape latency in the Morris water maze (p < 0.001). The extract dose-dependently suppressed brain AChE activity and elevated acetylcholine levels in scopolamine-treated mice. Furthermore, it attenuated oxidative stress, upregulated BDNF/TrkB signaling, modulated apoptotic protein expression (increased Bcl2, decreased Bax), and inhibited caspase activation, offering neuroprotection against scopolamine-induced neuronal damage. These findings highlight the potential memory functions of Neurocaf, supporting its further evaluation as a candidate functional food or dietary supplement for brain health.

Ischemic stroke remains a leading cause of mortality and disability worldwide, with limited therapeutic options that effectively target its complex pathophysiology. This study evaluates the neuroprotective potential of phloroglucinol (PH), a polyphenolic compound with known antioxidant and anti-inflammatory properties, in a rat model of focal cerebral ischemia induced by middle cerebral artery occlusion (MCAO). Animals were randomly assigned to different groups. Phloroglucinol was administered intraperitoneally at doses of 15 and 30 mg/kg, beginning immediately after a 1-hour MCAO injury and continuing once daily for 21 days. Treatment with phloroglucinol significantly improved neurological deficit, muscle strength, locomotor activity, and cognitive performance (Morris Water Maze (MWM) and Novel Object Recognition Test (NORT) conducted at the last week of study) compared to untreated MCAO rats. Biochemical analyses revealed that phloroglucinol reduced oxidative stress markers (malondialdehyde (MDA), nitrite), restored antioxidant defenses (glutathione (GSH) and catalase, and attenuated neuroinflammation by lowering interleukin-6 (IL-6) and tumor necrosis factor-α (TNF-α) levels. Additionally, phloroglucinol decreased cerebral infarct volume and preserved blood-brain barrier (BBB) integrity. However, it also improved the mitochondrial functions by increasing the gene expression of hypoxia-inducing factor 1 alpha (HIF-1α) and Transcription factor A, mitochondrial (TFAM), reducing caspase-3 activation and inducing nitric oxide synthase (iNOS) gene expression, and enhancing nuclear factor erythroid 2-related factor 2/ Heme oxygenase-1 (Nrf-2/HO-1) expression. Molecular docking studies suggested that phloroglucinol may exert its effects via interaction with the Kelch-like ECH-associated protein 1 (KEAP1)-Nrf-2 pathway. These findings highlight phloroglucinol as a promising multi-target neuro-protective agent for ischemic stroke, warranting further investigation for clinical translation.

Hepatic encephalopathy (HE), which develops as a result of liver failure, is an important neurological disorder involving inflammation and oxidative damage, with apoptosis and autophagy supported mainly by experimental evidence. In the current research, we researched the protective effects of oleuropein (OLE) in a thioacetamide (TAA)-induced HE model, particularly through the PI3K/Akt/mTOR signalling pathway. To execute the planned experimental design, Sprague Dawley rats (n = 28) were divided into four groups: Control, OLE, TAA, and TAA + OLE. OLE was administered orally (50 mg/kg) during a 14-day period, followed by intraperitoneal TAA (50 mg/kg) for 14 days in the TAA groups. Behavioral tests (open field and Y-maze) were used to determine cognitive and anxiety-like disorders in the rats. Oxidative stress indicators (MDA, SOD, and GSH), pro-inflammatory cytokines (IL-1β, IFN-γ, and TNF-α), autophagic and apoptotic processes (Caspase-3, Bcl-2, Beclin-1, LC3), PI3K/Akt/mTOR pathway proteins, and AQP4 levels were analyzed in the serum and tissue. Histopathological evaluation was used to evaluate tissue damage in the liver and brain. The results indicated that the TAA-activated PI3K/Akt/mTOR pathway was suppressed by OLE, oxidative damage, autophagy, apoptosis, and inflammation were reduced, and behavioral and histological improvements were achieved. These results suggest that OLE offers hepatoprotective effects and ameliorates HE-associated brain injury via the PI3K/Akt/mTOR pathway.