Posterior hypothalamic nucleus serotonin depletion facilitates spatial learning and increases power and coherence in the posterior hypothalamic-septal-hippocampal circuit in rat.

Netrin-3 rectifies diabetes-induced cognitive impairment by counteracting hippocampal oxidative stress and NLRP3 inflammasome activation.

Sevoflurane activates ATF4/NSUN7/PRKCD axis to induce neurotoxicity and cognitive impairment by promoting neuron mitochondrial fission.

MiR-372-3p alleviates isoflurane-induced cognitive dysfunction by targeting STAT3 to mitigate neuroinflammation and oxidative stress.

Optimization and validation of an animal model for perioperative neurocognitive disorders based on SAMP8 mice.

Cerebral ischemia-reperfusion injury is a prevalent complication following blood flow restoration in ischemic stroke, which induces severe neurological dysfunction via intricate oxidative stress and inflammatory cascades. Cerium oxide nanoparticles (CeO₂NPs), endowed with unique Ce³⁺/Ce⁴⁺ valence transition properties, exhibit mimetic activities of superoxide dismutase and catalase, enabling efficient scavenging of reactive oxygen species and attenuation of inflammatory responses. This study aimed to investigate the protective effects and underlying molecular mechanisms of CeO₂NPs against cerebral ischemia-reperfusion injury. First, the physicochemical properties and toxicity of CeO₂NPs were systematically characterized: dynamic light scattering (DLS) showed a polydispersity index (PDI) of 0.28 and a ζ-potential of -24.9 mV; transmission electron microscopy (TEM) confirmed a particle size range of 2-6nm; X-ray photoelectron spectroscopy (XPS) quantification demonstrated 100% Ce coverage on the particle surface. The Morris water maze test indicated no significant neurotoxicity at a dose of 0.4mg/kg. Subsequently, the therapeutic efficacy was evaluated using a MCAO mouse model. Behavioral assessments revealed that 24h after reperfusion, the CeO₂NPs-treated group exhibited behavioral performance more comparable to the normal group. Combined with histopathological analysis of brain tissues, these findings confirmed that CeO₂NPs significantly improved neurological function and alleviated brain tissue damage. Proteomics analysis further uncovered that CeO₂NPs mitigate oxidative damage and inflammation primarily by regulating the mitochondrial-mediated apoptotic pathway and superoxide dismutase-related oxidative stress responses. In conclusion, 2-6nm CeO₂NPs hold great promise as an effective neuroprotective agent for the treatment of cerebral ischemia-reperfusion injury, with their mechanism of action involving multiple cellular protective pathways.

Impaired autophagy from TRPV4 activation drives α-synuclein pathology in a Parkinson's disease model: A toxicological insight.

Disposable plastic-alcohol leachates as emerging Neurotoxicants: Evidence for the mir-330-3p/Acsl1 pathway in cognitive performance.

Role of NMDAR-NMNAT in sevoflurane exposure-induced learning memory deficits.

Symbiotic (L. acidophilus and Agave Inulin) Prevents Cognitive Impairment in High-Fat Diet/STZ Rats.

Exogenous rGDF11 ameliorates chronic stress-induced cognitive impairment by suppressing the accumulation of endogenous formaldehyde.

Prenatal immune challenge and perinatal high-fat/high-sugar diet: a double-hit model of neurodevelopmental vulnerability.

Acori tatarinowii Rhizoma-Curcumae Radix herbal pair ameliorates cognitive impairment and suppresses neuro-inflammation via Ca2+/CaMKKβ/AMPK/mTOR pathway in Alzheimer's disease.

Modified Kai-Xin-San ameliorates cognitive impairment in Alzheimer's disease model mice by regulating neuroinflammation and synaptic dysfunction.

Alterations in gray matter structure associated with cognitive decline in T1DM patients and mice: A voxel-based morphometry study.

Early-life exposure to endocrine-disrupting chemicals (EDCs) can interfere with brain development and contribute to long-term cognitive impairments. This study investigated whether hippocampal metabolite alterations at postnatal day 6 (PND6) are associated with behavioral outcomes in early adulthood following perinatal exposure to four EDCs: bisphenol F (BPF), butyl benzyl phthalate (BBzP), triphenyl phosphate (TPHP), and diisononyl cyclohexane-1,2-dicarboxylate (DINCH). Male and female rats were exposed in utero and during lactation, and hippocampal tissue was collected at PND6 for targeted metabolomics and untargeted lipidomics. Behavioral testing in adulthood using the Morris water maze assessed spatial learning (acquisition) and cognitive flexibility (reversal). BBzP exposure impaired acquisition learning, and BPF disrupted reversal performance in males. In females, both DINCH and TPHP led to increased latency during reversal. A multi-layered analytical framework was applied to explore associations between early metabolite and lipid profiles and later behavioral performance, including group-based comparisons, correlation analyses, and evaluation of biologically informed ratios. Results revealed sex- and domain-specific alterations in steroid and thyroid hormones, neurotransmitters, and PUFA-containing lipid classes, as well as changes in functional ratios and metabolite-metabolite coordination. These early metabolic disruptions were associated with increased escape latency in adulthood, suggesting long-term impacts on hippocampal function.

The Mitigating Effects of N-Acetylcysteine on TiO2 Nanoparticles-Induced Toxicity: Efficacy in Cytotoxicity Reduction in Vitro and Complexity in Vivo.

ABSTRACT Ethnopharmacological relevance Pyracantha crenulata, traditionally used in Himalayan folk medicine, valued for enhancing vitality, mental clarity, and combating age-related cognitive decline due to its antioxidant constituents. Aim This study evaluated the neuroprotective effect of hydroalcoholic extract of P. crenulata against aluminium chloride (AlCl3)-induced Alzheimer’s disease in rats. Materials and Methods Alzheimer’s pathology was induced using AlCl3, and rats were treated with P. crenulata extract (250 and 500 mg/kg) for 21 days. Cognitive and behavioural performance were assessed using the Morris Water Maze (MWM) and Elevated Plus Maze (EPM). Biochemical parameters, including oxidative stress markers (SOD), cholinesterase activity (AChE), and myeloperoxidase levels (MPO), were measured. Histopathological examination of the hippocampus and cerebral cortex was conducted. Results Aluminium intoxication led to marked deficits in learning and memory, as evidenced by performance in the Morris Water Maze and Elevated Plus Maze tests. Treatment with P. crenulata extract significantly enhanced spatial and long-term memory in a dose-dependent manner, with the higher dose producing the most pronounced improvement. Conclusion The findings of this study highlight the notable neuroprotective effects of P. crenulata, demonstrated through modulation of biochemical parameters and suppression of amyloid precursor protein and Tau, key pathological hallmarks of Alzheimer’s disease, further validated by histopathological evidence.

Alzheimer's disease (AD) is a debilitating neurodegenerative disorder characterized by cognitive decline and memory loss. Current treatments offer limited efficacy, necessitating the development of innovative multitarget therapeutic strategies. Here, we present N3,N5-bis(2-(5-methoxy-1H-indol-3-yl)ethyl)-2,6-dimethyl-4-(2-nitrophenyl)pyridine-3,5-dicarboxamide (HCM-01), a novel compound developed to target multiple neurodegenerative pathways implicated in AD. In vitro assays included MTT-based cell viability analyses performed in two complementary experimental settings: primary neuronal cultures and astrocyte-based in vitro cell culture models exposed to glutamate. In primary hippocampal neuronal cultures, glutamate exposure induced a statistically significant reduction in cell viability compared with vehicle-treated controls, consistent with glutamate-induced excitotoxicity. Under these conditions, HCM-01 treatment resulted in a statistically significant improvement in neuronal viability, showing a greater protective effect compared with donepezil and memantine. In contrast, in astrocyte-based in vitro cultures, the applied glutamate concentration did not induce overt cytotoxicity, in line with the intrinsic neuroprotective and glutamate-buffering role of astrocytes. Accordingly, astrocytic experiments were designed to assess functional modulation of glutamate-handling mechanisms rather than cell survival. Western blot analysis in C8-D1A astrocytic cells demonstrated increased expression of excitatory amino acid transporter 2 (EAAT2) following HCM-01 treatment compared with control and reference drug-treated groups, suggesting modulation of astrocyte-mediated glutamate homeostasis. In parallel, redox analyses revealed that HCM-01 improved oxidative/antioxidative balance, as evidenced by increased total antioxidant capacity (TAC) and reduced total oxidant status (TOS), supporting an indirect antioxidant contribution to its functional effects. In vivo behavioral assessment of HCM-01 in a streptozotocin (STZ)-induced Alzheimer's model in female Sprague-Dawley rats demonstrated that administration of HCM-01 at doses of 50 mg/kg orally (oral, P.O. and intraperitoneal, I.P.) and 100 mg/kg (P.O.), significantly improved cognitive and memory functions in the passive avoidance (PA), Morris water maze (MWM), and locomotor activity tests. Moreover, histopathological and immunohistochemical analyses of different hippocampal regions revealed reduced neuronal damage, attenuation of tau pathology, antiamyloidogenic effect, and restoration of cholinergic function. Complementary in silico studies, including molecular docking, molecular dynamics simulations (MDS), and free energy calculations, suggested potential interactions of HCM-01 with the allosteric site of EAAT2. Taken together, these findings suggest that HCM-01 exerts neuroprotective effects against glutamate-induced excitotoxicity in primary hippocampal neurons while additionally modulating glutamatergic homeostasis and redox balance through functional mechanisms in astrocyte-based models, supporting its relevance as a multitarget preclinical candidate for early stage AD mechanisms.

Sepsis-associated encephalopathy (SAE) is one of the common and severe complications of sepsis, but the pathogenesis remains to be clarified. It has been reported that Treml4 was upregulated in myeloid cells of septic mice, and inhibition of Treml4 was protective against sepsis-induced mortality. But the role of Treml4 on SAE remains unclear. Cecal ligation and puncture (CLP) was carried out to establish a murine sepsis model. The hippocampal tissues and blood samples of mice were collected for the detection of inflammatory factors (IL-1β, IL-6, TNF-α), oxidative stress damage (MDA, SOD), and WB analysis. Brain tissues were collected for immunofluorescence staining to localize the Treml4 receptor and assess the activation and polarization of microglia. Learning and memory abilities of mice were detected with the Morris water maze(MWM) test. In vitro experiments were conducted using small interfering RNA (siRNA) technology in LPS-stimulated microglia to explore the potential mechanism of Treml. Treml4 was upregulated in the hippocampus of CLP mice, associated with the activation of Lyn, Syk and ERK. Knockout of Treml4 significantly reversed the phosphorylation of Lyn, Syk, and ERK in the hippocampus, alleviated inflammation and oxidative stress damage, and protected against memory dysfunction caused by sepsis. Similarly, knockdown of Treml4 could inhibit LPS-induced BV-2 cell activation, and the Lyn agonist Tolimidone (CP-26154) could reverse this effect in vitro. Treml4-mediated inflammatory and oxidative stress injury is crucial in the development of sepsis encephalopathy, indicating the potential role of Treml4 as a target for preventing and treating SAE.