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Obesity and excessive weight gain have emerged as significant global health concerns in recent years and are often comorbid with numerous contemporary diseases, including cardiovascular disorders, diabetes, and cognitive impairments. L-carnitine, a vital cofactor in mitochondrial energy metabolism, possesses potent antioxidant and anti-inflammatory properties that merit investigation for mitigating obesity-associated neuronal damage. Consequently, this study investigated the potential neuroprotective effects of L-carnitine on anxiety- and depression-like behaviors in adolescent rats subjected to neonatal monosodium glutamate (MSG) exposure, a model known to induce obesity and associated neurobehavioral alterations. Neonatal rats received MSG (4 g/kg, s.c.) on alternate postnatal days (PND) 2-10. Subsequently, L-carnitine (200 mg/kg) was administered via oral gavage daily from PND 60 to 81 (subchronic treatment). Anxiety- and depression-like behaviors were assessed using the Forced Swim Test (FST), Elevated Plus Maze (EPM), and Open Field Test (OFT). All molecular and histological analyses were conducted in the prefrontal cortex (PFC), a region selected for its susceptibility to excitotoxicity and critical role in emotional regulation. Oxidative stress was evaluated through measurements of total oxidant and antioxidant levels. To elucidate the underlying molecular mechanisms, gene expression analyses focused on neuronal survival and apoptosis (BDNF, Bax, Bcl-2), while immunohistochemical evaluations targeted neuroinflammation and cell death pathways (TNF-α, Caspase-3, IL-1β, and Bcl-2). The findings reveal that neonatal MSG exposure leads to pronounced anxiety- and depression-like behaviors, accompanied by metabolic dysregulation, oxidative stress, neuroinflammation, and apoptosis. Although L-carnitine treatment did not reverse obesity-related metabolic alterations, it exhibited notable sustained anxiolytic effects. The neuroprotective potential of L-carnitine was further supported by its ability to reduce cortical neuroinflammation and neurodegerenative damage through suppression of proinflammatory cytokines and restoration of antioxidant balance. Overall, this study offers valuable insights into the cognitive, genetic, and histological outcomes associated with obesity-related mood disturbances and contributes to understanding the complex biological mechanisms underlying these conditions. Show less

Diabetic neuropathic pain (DNP) is a common and debilitating complication of diabetes that profoundly reduces patient quality of life. Despite extensive research, current treatments remain largely symptomatic, with limited efficacy and significant side effects. Microglia act as pivotal mediators of DNP through RAGE/TLR4/NLRP3-driven IL-1β and BDNF release that amplifies spinal pain signaling. Microglia respond directly to hyperglycemia-induced cues such as advanced glycation end-products, reactive oxygen species, ATP, and pro-inflammatory signals, becoming activated and releasing cytokines, chemokines, and neuromodulators including BDNF that amplify spinal pain signaling. This review synthesizes recent insights into the molecular triggers of microglial activation such as RAGE, TLRs, purinergic receptors, and inflammasomes and the downstream intracellular pathways including NF-κB, MAPK, PI3K/Akt, and BDNF-TrkB that drive neuroinflammation. We further examine neuroimmune crosstalk, including bidirectional microglia-neuron and microglia-astrocyte signaling, which sustains central sensitization. Translational studies linking these pathways to human DNP are evaluated, along with novel technologies that illuminate microglial phenotypes. Emerging therapeutic strategies focus on inhibition of these pathways, including RAGE antagonists and purinergic receptor blockers. However, a critical translational gap persists owing to insufficient human validation of microglial biomarkers and the limited fidelity of current animal models. By integrating basic and clinical findings, we underscore the promise of microglia-focused interventions to complement traditional analgesics and ultimately improve outcomes in DNP patients. Show less

To evaluate the preventive effect of dipeptidyl peptidase-4 inhibitors (DPP-4i) on post-stroke cognitive impairment (PSCI) in patients with type 2 diabetes mellitus (T2DM) and concurrent acute ischemic stroke (AIS). A retrospective cohort study was conducted on 236 patients with T2DM+AIS recruited from April 2021 to October 2024. Patients were grouped based on DPP-4i use: an observation group (107 cases) with DPP-4i therapy and a control group (129 cases) without. Patients' baseline demographics, clinical features, laboratory indices, and follow-up data were extracted from the electronic medical record system. The primary outcome measure was the incidence of PSCI, defined as a Montreal Cognitive Assessment Scale (MoCA) score <26 at six months after AIS. Secondary outcomes included inflammatory cytokines, oxidative stress markers, neuroprotective factors (BDNF), glycemic metabolism indicators, and life quality [Barthel Index (BI), Functional Independence Measure (FIM), and Instrumental Activities of Daily Living (IADL)]. At 6 months after AIS, the incidence of PSCI was significantly lower in the observation group than in the control group (P<0.05). Furthermore, inflammatory and oxidative stress marker levels were decreased whereas BDNF level was significantly elevated in the observation group compared to the control group (all P<0.05). According to the quality-of-life assessment, patients receiving DPP-4i had higher BI, FIM, and IADL scores (P<0.05), along with a lower all-cause readmission rate (P<0.05). Subgroup analysis indicated that different DPP-4i types (e.g., sitagliptin, saxagliptin) had consistent cognitive protective effects (P>0.05). DPP-4i can lower PSCI risk in T2DM+AIS patients. Its mechanism involves multi-dimensional effects like anti-inflammation, anti-oxidation, insulin sensitivity enhancement, and neuroprotection. Show less

Buchanania lanzan Spreng. (Anacardiaceae) seeds (BLHA) are the cheaper alternative to almonds used in the confectionery industry. The flour powder of seeds is used as a thickening agent to prepare sauces and flavourings for a batter. The socioeconomic importance of this species lies in its medicinal properties for curing diabetes. The study explored the multifaceted neuroprotective role of BLHA (500 mg/kg) in hyperlipidic high-fat diet streptozotocin (HFD/STZ)-induced type2 diabetic neuropathy (T2DN) rats via glucose metabolism, insulin resistance, and inflammation to mitigate nerve damage. Molecular docking analysis was performed to identify specific molecular targets of bioactive compounds in T2DN pathogenesis. Serum diabetic parameters, such as serum glucose (SG), insulin (SI), total protein (TP), triglycerides (TG), blood urea nitrogen (BUN), creatinine (Cr), HDL-C, and LDL-C, were studied. A strong correlation between HbA1C and insulin resistance assessed by HOMA-IR. Oxidative stress triggers the production of free radicals, so the antioxidant indicators in serum, tissues, and proinflammatory cytokines in the liver, brain, and pancreas were measured in T2DN rats. Effects on neurochemicals, BACE1, Aβ BLHA at 500 mg/kg significantly improved hyperglycemic (SG, SI, HOMA-IR, HbA1C), hepatic (AST, ALT, ALP, TP, TB), dyslipidemic (TC, TG, HDL-C, LDL-C), and kidney function markers (creatinine, BUN) in T2DN rats. BLHA restored oxidative (CAT, GSH, SOD, MDA) and cytokine markers (TNF-α, IL6) in the liver, pancreas, and brain cortex. Oxidative stress-impaired neurotransmitters were alleviated by enhancing cholinesterase (AChE, BChE) and BACE1 activities, and by ameliorating Aβ The multifaceted actions of dietary polyphenols, antioxidants, and antidiabetic compounds (Catechol, 2-Hydroxy-5-methylbenzaldehyde, 8-Octadecenoic acid methyl ester, n-Hexadecanoic acid, 2-hydroxy-1-(hydroxymethyl)ethyl ester, β-Sitosterol, Hexadecenoic acid methyl ester) in BLHA modulated glucose metabolism, restored HOMA-IR, and reduced inflammation by protecting against oxidative stress, as a result, it improved neurotransmission and reduced neuropeptide aggregation in T2DN rats. The dock score of β-sitosterol (AChE: -12.7; BChE: -14.8; IL6: -9.8; and Atp1a3: -13.3 kcal/mol) correlated with the experimental evidence. Show less

The role of central histamine in diabetes induced behavioral despair is still an enigma. Therefore, the current research explored the plausible impact of the central histaminergic activity on the expression of diabetes-induced behavioral despair in mice using the tail suspension test (TST) and surose preference test (SPT) along with changes in the levels of BDNF and phosphorylated CREB (pCREB) in the whole brain, hippocampus, PFC, and amygdala. Post-streptozotocin (STZ) (200 mg/kg, i.p.) injection, on the 4 Show less