Neurochemical Research最新文献

{"title":"Correction: Salidroside Exerts Neuroprotective Effects via Inhibiting Ferroptosis in Mice with Traumatic Brain Injury","authors":"Yuxing Huang, Yijia He, Xiaolong Zhao, Yongjie Zou, Weijun Ding, Linjie Wei","doi":"10.1007/s11064-025-04479-8","DOIUrl":"10.1007/s11064-025-04479-8","url":null,"abstract":"","PeriodicalId":719,"journal":{"name":"Neurochemical Research","volume":"50 4","pages":""},"PeriodicalIF":3.8,"publicationDate":"2025-07-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144599066","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"In Vitro Assessment of Cholinesterase Inhibition and Neuroprotective Effects of Elaeocarpus angustifolius Blume Against Amyloid-Beta Peptide-Induced Toxicity in SH-SY5Y and BV-2 Cells","authors":"Zeenath Banu,&nbsp;Nihar Ranjan Das","doi":"10.1007/s11064-025-04478-9","DOIUrl":"10.1007/s11064-025-04478-9","url":null,"abstract":"<div><p>Alzheimer’s disease (AD) is a progressive neurodegenerative disorder primarily characterized by memory impairment and cognitive decline. Pathophysiological mechanisms contributing to AD include oxidative stress, increased acetylcholinesterase activity, neuroinflammation, and the accumulation of hyperphosphorylated tau proteins and amyloid-β (Aβ) plaques in the brain. The shortcomings of existing therapeutic approaches have necessitated the exploration of alternative treatment strategies. <i>Elaeocarpus angustifolius</i> Blume, traditionally used for neurological disorders, has been investigated for its neuroprotective potential through its alkaloid-rich fraction. This study evaluated the acetylcholinesterase (AChE) and butyrylcholinesterase (BuChE) inhibitory activities of <i>E. angustifolius</i> alkaloid-rich fraction (EAF) and its protective effects against Aβ₁₋₄₂-induced cytotoxicity in human neuron-like SH-SY5Y cells and murine microglial BV-2 cells using the MTT assay. The results demonstrated that for AChE and BuChE, EAF showed significant inhibition with IC50 of 145.1 ± 4.782 µg/mL and 165.8 ± 1.10 µg/mL, respectively. In the MTT assay, EAF effectively mitigated Aβ₁₋₄₂-induced cytotoxicity in a dose-dependent manner, with the highest dose (100 µg/mL) restoring viability from 67.91 to 75.31% in SH-SY5Y cells and from 60.29 to 76.01% in BV-2 cells. From these results, it is apparent that EAF has anticholinesterase and neuroprotective properties. However, further research on this may help decipher underlying mechanisms before establishing EAF as an effective alternative in treating AD.</p></div>","PeriodicalId":719,"journal":{"name":"Neurochemical Research","volume":"50 4","pages":""},"PeriodicalIF":3.8,"publicationDate":"2025-07-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144590131","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"ALG13 Deficiency and Epilepsy-Related Cognitive Impairment: Role of the DDIT4-Mediated PI3K/AKT/mTOR Pathway","authors":"Peng Gao,&nbsp;Tao Sun,&nbsp;Xin Qian,&nbsp;Anhong Liu,&nbsp;Shuxiang Li,&nbsp;Yang Xia,&nbsp;Jing Zhang,&nbsp;Hui Ma","doi":"10.1007/s11064-025-04476-x","DOIUrl":"10.1007/s11064-025-04476-x","url":null,"abstract":"<div><h3>Objective</h3><p>This study aimed to investigate the impact of ALG13 deficiency on cognitive function in mice.</p><h3>Methods</h3><p>Cognitive behavior in <i>Alg13</i> knockout (KO) mice was assessed using the IntelliCage system (free exploration, nosepoke learning, spatial learning, and reversal learning) and the Smart 3.0 system (open-field activity, novel object recognition, and spatial object recognition). Social cognition was evaluated through three-chamber sociability, novelty preference, and social recognition memory tests. RNA sequencing and bioinformatic analyses were conducted to explore potential molecular mechanisms.</p><h3>Results</h3><p>When housed separately, <i>Alg13</i> KO mice exhibited impaired free exploration, nosepoke learning, and spatial reversal learning compared to wild-type (WT) controls; however, co-housing eliminated these differences, with no significant disparities in free exploration, nosepoke learning, spatial learning, or spatial reversal learning. Notably, <i>Alg13</i> KO mice had significantly lower error rates in spatial position learning and spatial position reversal learning. In behavioral analyses using Smart 3.0 tracking, <i>Alg13</i> KO mice were found to exhibit diminished locomotor activity in the open-field task, impaired novel object recognition, and reduced spatial novelty exploration. In social cognition tests, both WT mice and <i>Alg13</i> KO mice showed a preference for novel stimuli, but WT mice showed superior learning abilities compared to <i>Alg13</i> KO mice. Furthermore, downregulation of the hub gene <i>Ddit4</i> and activated PI3K/AKT/mTOR signaling pathway were identified in RNA sequencing.</p><h3>Conclusion</h3><p>ALG13 deficiency results in cognitive impairment in mice, potentially mediated by dysregulation of the DDIT4-PI3K/AKT/mTOR signaling pathway.</p></div>","PeriodicalId":719,"journal":{"name":"Neurochemical Research","volume":"50 4","pages":""},"PeriodicalIF":3.8,"publicationDate":"2025-07-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144574644","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"ALDH2 Attenuates Blood-Brain Barrier Injury Induced by Cerebral Ischemia/Reperfusion via Alleviating ROS/NLRP3 Inflammasome Axis","authors":"Jie Gao,&nbsp;Liya Wang,&nbsp;Meng Qin,&nbsp;Yujiao Gao,&nbsp;Siyu Sun,&nbsp;Hao Wang,&nbsp;Qin Gao,&nbsp;Ying Yu","doi":"10.1007/s11064-025-04472-1","DOIUrl":"10.1007/s11064-025-04472-1","url":null,"abstract":"<div><p>An important factor influencing the prognosis of ischemic stroke is impairment of the blood-brain barrier (BBB). Additionally, oxidative stress and inflammation contribute significantly to the breakdown of the BBB during ischemic stroke reperfusion. Strong evidence suggested that Aldehyde dehydrogenase 2 (ALDH2) may have protective properties and reduce oxidative stress and inflammatory reactions in neurological conditions. Therefore, in order to examine the impact of ALDH2 on BBB integrity after ischemia/reperfusion (I/R) damage, we constructed the cerebral artery occlusion/reperfusion (MCAO/R) model and the oxygen–glucose deprivation/reperfusion (OGD/R) model. According to our findings, ALDH2 activation enhanced cell viability in bEnd.3 cells treated with OGD/R and reduced infarct area and neurological impairments in MCAO/R animals. Furthermore, both in vitro and in vivo, ALDH2 suppressed inflammation-related factors IL-1β and IL-18, as well as oxidative stress and the expression of the NOD-like receptor thermal protein domain associated protein 3 (NLRP3) inflammasome. In addition, bEnd.3 cells exhibited a reduced reactive oxygen species (ROS) generation function of ALDH2. Moreover, we noticed that ALDH2 boosted the expression of the tight junctions (TJs) zonula occludens-1 (ZO-1) and Occludin to control BBB function. In summary, ALDH2 protected against cerebral I/R injury and BBB destruction, and this protection was related to the ROS/NLRP3 axis.</p><h3>Graphical Abstract</h3><div><figure><div><div><picture><source><img></source></picture></div></div></figure></div></div>","PeriodicalId":719,"journal":{"name":"Neurochemical Research","volume":"50 4","pages":""},"PeriodicalIF":3.8,"publicationDate":"2025-07-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144551647","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"D-ribose-L-cysteine Attenuates manganese-induced Oxidative Stress, Neuromorphological Deficits, Bax/Bcl-2 Response and TNF-α/ERK Signalling in Rats","authors":"Happiness O. Inyang,&nbsp;Uchenna K. Ezemagu,&nbsp;Stephen O. Okori,&nbsp;Olayemi K. Ijomone,&nbsp;Omamuyovwi M. Ijomone","doi":"10.1007/s11064-025-04466-z","DOIUrl":"10.1007/s11064-025-04466-z","url":null,"abstract":"<div><p>Manganese (Mn), though an essential trace element, can become neurotoxic after excessive exposure. Established mechanisms of Mn neurotoxicity include oxidative stress, apoptotic signalling, and inflammatory responses. D-ribose-L-cysteine (RibCys), a cysteine derivative, is reported to mitigate oxidative damage. In this study, we investigated its effects on B-cell lymphoma 2-associated X protein (Bax)/B-cell lymphoma 2 (Bcl-2) apoptotic signaling, tumor necrosis factor-alpha (TNF-α) inflammatory response, and extracellular signal-regulated kinase (ERK) pathway across various brain regions. Adult male Wistar rats were treated with saline (control), Mn (25 mg/kg intraperitoneally for 2 weeks, 8 doses at 48-hour intervals), RibCys (200 mg/kg orally for 2 weeks), or both Mn and RibCys. Biochemical assays for oxidative stress and antioxidant activity, Golgi staining for dendritic morphology, and immunohistochemistry for key protein markers were performed. Results showed that RibCys reduced Mn-induced distortions in brain neurochemistry and dendritic morphology. Mn increased lipid peroxidation, myeloperoxidase, and nitric oxide levels while decreasing glutathione peroxidase and sulfhydryl content, and these effects were attenuated by RibCys. Mn also disrupted dendritic arborization, which improved with RibCys treatment. Furthermore, Mn exposure elevated Bax/Bcl-2, TNF-α, and ERK1/2 expression in selected brain regions. RibCys co-administration mitigated these molecular alterations. Our findings suggest that RibCys is a promising therapeutic agent against Mn-induced neurotoxicity with potential for broader application. A notable limitation of this study was the absence of direct measurements of reduced and oxidized glutathione, and cysteine. Future studies should include these key antioxidant markers, assess long-term outcomes of RibCys treatment, and incorporate female animal models to evaluate potential sex-specific responses to Mn toxicity and intervention.</p></div>","PeriodicalId":719,"journal":{"name":"Neurochemical Research","volume":"50 4","pages":""},"PeriodicalIF":3.8,"publicationDate":"2025-06-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144525924","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Palmitic Acid Induces Dynamic Time-Dependent Alterations in HDACs, Neuronal Chromatin Acetylation, and Gene Expression","authors":"Saúl Santiago Rueda-Díaz,&nbsp;Iker Francisco Soto-Santarriaga,&nbsp;Karla Torres-Arciga,&nbsp;Valeria Melissa García-Cruz,&nbsp;Rodrigo González-Barrios,&nbsp;Manuel Flores-León,&nbsp;Clorinda Arias","doi":"10.1007/s11064-025-04469-w","DOIUrl":"10.1007/s11064-025-04469-w","url":null,"abstract":"<div><p>Chronic consumption of high fat diets (HFD) is a risk factor for the development of metabolic diseases such as obesity and diabetes, and it is also associated with cognitive impairment and Alzheimer´s disease. Palmitic acid (PA) is a major component of HFD, and high concentrations of this saturated fatty acid exerts pleiotropic actions in cells. The PA effects have been largely studied in peripheral tissues where is considered a driving force for the development of many metabolic diseases such as obesity, insulin resistance and Type II diabetes. In the brain, particularly in neurons, it is able to increase oxidative metabolism, induce insulin resistance, and alter gene expression. However, little is known about how PA-induced metabolic alterations may affect gene expression mechanisms in neurons. One of the most studied PA-dependent mechanisms is associated with the lipid-induced activation of the transcription factors, PPAR-γ and PGC-α, but fewer studies have analyzed the PA-dependent regulation of epigenetic mechanisms. In this study, we identified PA-linked changes in the class I histone deacetylases (HDACs) content associated with chromatin acetylation and with differential expression of the <i>BDNF-</i>encoding gene and the non-coding retrotransposon, <i>LINE1</i> in differentiated human neuroblastoma cells.</p></div>","PeriodicalId":719,"journal":{"name":"Neurochemical Research","volume":"50 4","pages":""},"PeriodicalIF":3.8,"publicationDate":"2025-06-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12208982/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144525926","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Activation of the TrkA/Ras-MAPK/ERK Signaling Pathway via Carbon Quantum Dot Mimetics for Enhanced Peripheral Nerve Regeneration","authors":"Faranak Hasanpour,&nbsp;Saber Zahri,&nbsp;Arash Abdolmaleki,&nbsp;Asadollah Asadi","doi":"10.1007/s11064-025-04470-3","DOIUrl":"10.1007/s11064-025-04470-3","url":null,"abstract":"<div><p>Peripheral nerve injuries (PNIs) present a significant clinical challenge, often resulting in impaired motor and sensory function. While the peripheral nervous system possesses regenerative capacity, severe injuries necessitate intervention to promote effective recovery. This study investigated the efficacy of novel PCL/Tragacanth scaffolds functionalized with amino acid-modified carbon quantum dots (CQDs) for peripheral nerve regeneration. The CQD was designed to mimic the action of nerve growth factor (NGF) by binding to TrkA receptors and activating the downstream Ras-MAPK/ERK signaling pathway, crucial for neuronal survival and differentiation. In vitro studies using PC12 cells demonstrated that the scaffolds incorporating amino acid-modified CQD significantly enhanced cell viability, neurite outgrowth, and expression of genes associated with neuronal differentiation (c-Jun, ERK1/2). Furthermore, in vivo evaluation in a rat sciatic nerve injury model revealed that these scaffolds promoted axonal regeneration, myelination, and improved motor function recovery, as assessed by the sciatic functional index (SFI). The enhanced regenerative capacity observed with the amino acid-modified CQD-functionalized scaffolds is attributed to their ability to provide sustained activation of the TrkA/Ras-MAPK/ERK signaling pathway, mimicking the beneficial effects of NGF. These findings highlight the potential of this novel biomaterial for developing effective therapeutic strategies for peripheral nerve repair.</p></div>","PeriodicalId":719,"journal":{"name":"Neurochemical Research","volume":"50 4","pages":""},"PeriodicalIF":3.8,"publicationDate":"2025-06-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144525923","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Propofol Modulates Microglial Glucose Metabolism Via the AMPK/HIF-1α Signaling Pathway To Ameliorate ECS-induced Cognitive Deficits in Depressive-like Rats","authors":"Mou Zou,&nbsp;Su Min,&nbsp;Ruiyang Hong,&nbsp;Jia Huang,&nbsp;Dongyu Zhou,&nbsp;Yun Liang","doi":"10.1007/s11064-025-04473-0","DOIUrl":"10.1007/s11064-025-04473-0","url":null,"abstract":"<div><p>Propofol can partly ameliorate electroconvulsive shock (ECS)-induced learning and memory impairment by restoring synaptic plasticity. However, the exact mechanism is unknown. Microglia exert different immune functions by regulating their glucose metabolism, which is closely related to synaptic plasticity. We aimed to investigate whether the mechanism underlying the cognitive enhancement effects of propofol is associated with microglial glucose metabolism. Rats depression model was established by chronic unpredictable mild stress (CUMS). Sucrose preference test (SPT) and open field test (OFT) were used to detect anhedonia and anxiety-like behaviors in rats, respectively. Morris water maze (MWM) was used to evaluate the spatial learning and memory ability of rats. Transmission electron microscopy, immunofluorescence, enzymatic activity assays, Western blotting, and RT-qPCR were employed to evaluate hippocampal synaptic structural integrity, microglial glucose metabolism, and the expression of glycolytic regulators p-AMPK/AMPK and HIF-1α. The AMPK inhibitor compound C was used for reverse validation. Propofol attenuated the ECS-induced reduction of hippocampal synaptic proteins PSD-95 and SYN1, suppressed the upregulation of pro-inflammatory cytokines TNF-α and IL-1β, and reduced microglial activation. It also reduced the key glycolytic enzymes in microglia, increased AMPK expression, and decreased HIF-1α expression, thereby improving learning and memory impairment in ECS-treated rats. Compound C reversed propofol’s neuroprotective effect. ECS-induced learning and memory deficits in depressive-like rats are associated with increased microglial glycolysis via the AMPK/HIF-1α pathway, a metabolism process that could be mitigated by propofol.</p></div>","PeriodicalId":719,"journal":{"name":"Neurochemical Research","volume":"50 4","pages":""},"PeriodicalIF":3.8,"publicationDate":"2025-06-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12209389/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144525927","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"MicroRNA-361-3p Regulates Autophagy and Apoptotic Processes by Regulating PI3K/Akt Signaling in Parkinson’s Disease","authors":"Pingting Chen,&nbsp;Jing Yang,&nbsp;Yixuan Xu,&nbsp;Jinli Chen,&nbsp;Weichen Zeng,&nbsp;Jimei Bu,&nbsp;Junfeng Wu,&nbsp;Ying Huang,&nbsp;Jie Li","doi":"10.1007/s11064-025-04435-6","DOIUrl":"10.1007/s11064-025-04435-6","url":null,"abstract":"<div><p>MicroRNAs are closely related to the pathogenesis of Parkinson’s disease (PD). The purpose of this study was to explore the effects of microRNA (miR)-361-3p on apoptosis and autophagy in 1-methyl-4-phenylpyridinium ion (MPP⁺) induced PD cell models, and its potential mechanisms. SH-SY5Y cells were induced by 1.0 mM MPP⁺ for 24 h to establish a PD cell model in vitro, and the expression level of miR-361-3p was regulated by cell transfection. Cell viability was detected by the Cell Count Kit (CCK)-8 method. Apoptosis was evaluated by flow cytometry. Inflammatory factors were detected by enzyme-linked immunosorbent assay (ELISA). The changes of autophagy-associated proteins (Beclin 1, LC3I, and LC3II) and PI3K/Akt signaling pathway-associated proteins (p-PI3K and p-Akt) were detected by Western blot. The target genes of miR-361-3p were predicted and functionally annotated by the bioinformatics method. The interaction between miR-361-3p and its target gene <i>PFKFB3</i> was verified by the luciferase reporter gene. With the increase of MPP⁺ concentrations, the expression level of miR-361-3p and cell viability decreased gradually. In MPP⁺ induced SH-SY5Y cells, upregulation of miR-361-3p significantly improved cell survival and reduced apoptosis, while downregulating autophagy protein Beclin 1, LC3II/LC3I ratio, and increasing proteins p-PI3K/PI3K and p-Akt/Akt ratio. In addition, upregulation of miR-361-3p inhibited the expression of <i>PFKFB3</i>, while further overexpression of <i>PFKFB3</i> negated the protective effect of miR-361-3p overexpression on MPP⁺ induced cells. This study showed that miR-361-3p was reduced in the PD cell model, and overexpression of miR-361-3p inhibited PD damage by regulating <i>PFKFB3</i> and activating the PI3K/Akt signaling pathway.</p></div>","PeriodicalId":719,"journal":{"name":"Neurochemical Research","volume":"50 4","pages":""},"PeriodicalIF":3.8,"publicationDate":"2025-06-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144525925","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Multidimensional Evaluation of the Streptozotocin-Induced Alzheimer's Model: Integrating Molecular, Histopathological, and Behavioral Correlates Over Time.","authors":"Amir Bavafa, Gholam Hossein Meftahi, Gila Pirzad Jahromi","doi":"10.1007/s11064-025-04467-y","DOIUrl":"10.1007/s11064-025-04467-y","url":null,"abstract":"<p><p>Alzheimer's disease (AD) is characterized by cognitive deterioration, oxidative stress and neuroinflammation. Reliable preclinical models for sporadic AD are lacking. The intracerebroventricular (ICV) streptozotocin (STZ) model simulates pathology of sporadic AD; its timeline remains ambiguous. We assessed multiple endpoints in male Wistar rats 1 and 3 months post-ICV STZ (3 mg/kg; n = 72; control, sham, STZ). Spatial and associative memory was tested via the Morris Water Maze and Passive Avoidance Task. Hippocampal superoxide dismutase (SOD), tumor necrosis factor-α (TNF-α), and brain-derived neurotrophic factor (BDNF) were measured by ELISA; neuronal integrity and amyloid deposits by hematoxylin-eosin (H&E) and Congo red staining. STZ groups (3-months vs. 1-month) exhibited cognitive deficits: increased escape latency (80.14 ± 5.75 vs. 65.68 ± 11.51 s; P = 0.008), decreased time in the target quadrant (7.32 ± 0.71 vs. 11.6 ± 1.99 s; P = 0.019), platform crossings (0.83 ± 0.4 vs. 2.5 ± 0.83; P < 0.001) and step-through latency (3.89 ± 1.14 vs. 12.43 ± 3.28 s; P = 0.011). SOD activity decreased (6.28 ± 0.76 vs. 10.11 ± 1.26 U/mg; P = 0.015), TNF-α increased (71.17 ± 2.16 vs. 58.06 ± 2.22 pg/mg; P = 0.004) and BDNF declined (47.09 ± 9.21 vs. 86.83 ± 8.51 pg/mg; P < 0.001). Histology revealed neuronal shrinkage, vacuolation and amyloid deposits in 3-months STZ rats. The ICV STZ model recapitulates AD features: cognitive decline, oxidative stress, neuroinflammation and compromised neurotrophic support. Limitations such as lack of neurofibrillary tangles and sex evaluations require investigation. Studies exploring tau pathology, sex differences, and long-term dynamics may refine therapeutic strategies.</p>","PeriodicalId":719,"journal":{"name":"Neurochemical Research","volume":"50 4","pages":"214"},"PeriodicalIF":3.8,"publicationDate":"2025-06-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144504358","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}