Neurochemical Research最新文献

{"title":"7-Hydroxyflavone Attenuates Amyloid-β-Induced Alzheimer’s Disease-Like Pathology Through Modulation of ROS/NLRP3 Inflammasome Signaling","authors":"Debarati Rakshit,&nbsp;Awanish Mishra","doi":"10.1007/s11064-026-04942-0","DOIUrl":"10.1007/s11064-026-04942-0","url":null,"abstract":"<div><p>Alzheimer’s disease (AD), the widely recognised neurodegenerative disease with no proper cure to date, is typified by memory decline. Apart from the amyloid hypothesis and cholinergic dysfunction, neuroinflammation is also a key factor behind AD. 7-Hydroxyflavone (7HF), a flavonoid, possesses antioxidant, anti-inflammatory, and neuroprotective activities and remains unexplored in AD. Thus, in our study, we aimed to investigate the efficacy of 7HF against amyloid beta (Aβ)-induced AD in mice. Target acquisition for AD- and 7HF-related targets was performed, and gene ontology enrichment analysis was conducted using network pharmacology. 7HF was docked with AChE and NLRP3 proteins. The effect of 7HF was evaluated on Aβ-induced cytotoxicity, AChE activity and proinflammatory cytokines in Neuro2a (N2a) cells. Aβ₁₋₄₂ was injected intracerebroventricularly in mice to induce AD, and mice were treated with 7HF (5, 10 &amp; 20 mg/kg/day; p.o.) for 28 days. Behavioural assessments were performed during the last week of the study, followed by sacrifice and brain collection for further biochemical, molecular, and histological evaluations. 7HF shared targets with AD and exhibited a highly interconnected protein-protein network, with enriched ontology parameters linked to neuronal function. 7HF showed good binding affinity with AChE and NLRP3 proteins. It reduced Aβ-induced cytotoxicity, AChE activity, and proinflammatory cytokine levels in N2a cells. Treatment with 7HF improved the Aβ-induced memory deficits in mice. It also reduced pro-oxidant and AChE activity, as well as the molecular levels of NLRP3, ASC, cleaved caspase-1, and pro-inflammatory cytokines in the Aβ-induced mouse brain. Amyloid-associated structures in the Aβ-induced mouse brain were also reduced by 7HF intervention. These observations suggest that 7HF might have ameliorated AD-like pathology by reducing AChE activity, ROS levels, NLRP3-related neuroinflammatory markers, ultrastructural changes, and amyloid burden in Aβ-induced mice.</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":"51 6","pages":""},"PeriodicalIF":4.5,"publicationDate":"2026-11-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149338245","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":"SP1-Mediated Transcriptional Induction of LCN2 Contributes to Ferroptosis-Related Astrocytic Injury After Intracerebral Hemorrhage","authors":"Yifan Li,&nbsp;Wei Jiang,&nbsp;Mengtan Cai,&nbsp;Fangtian Zhong,&nbsp;Ming Dong","doi":"10.1007/s11064-026-04949-7","DOIUrl":"10.1007/s11064-026-04949-7","url":null,"abstract":"<div><h3>Background</h3><p>Intracerebral hemorrhage (ICH) causes secondary brain injury involving ferroptosis and neuroinflammation. Lipocalin-2 (LCN2) is rapidly induced after ICH, but the mechanism underlying its early induction in astrocytes remains unclear. This study examined whether specificity protein 1 (SP1) regulates LCN2 expression and contributes to ferroptosis-related astrocytic injury.</p><h3>Methods</h3><p>Potential transcription factors regulating <i>Lcn2</i> were screened with HOMER and JASPAR. The SP1-LCN2 relationship was examined in a collagenase-induced ICH model, hemin-treated CTx-TNA2 cells, and primary rat astrocytes. Plicamycin (PLI) was used to suppress SP1-associated transcriptional activity, and LCN2 overexpression was used for rescue experiments. SP1 occupancy at the <i>Lcn2</i> promoter was assessed by ChIP-qPCR. Ferroptosis-related changes were evaluated by molecular, biochemical, histological, and ultrastructural analyses.</p><h3>Results</h3><p>SP1 and LCN2 increased early after ICH, with the strongest fluorescence signals detected in astrocyte-associated regions. PLI reduced SP1 and LCN2 expression and attenuated iron accumulation, lipid peroxidation, mitochondrial abnormalities, and inflammatory cytokine changes. Hemin increased SP1 enrichment at the <i>Lcn2</i> promoter, and a similar SP1-LCN2 response was observed in primary astrocytes. LCN2 overexpression partly reversed the PLI-induced increases in SLC7A11 and GPX4 and the decrease in ACSL4 expression. It also partly reversed the changes in KEAP1-NRF2-associated proteins.</p><h3>Conclusion</h3><p>Our findings support SP1-dependent transcriptional activation of LCN2 as a mechanism underlying its early induction after ICH. The partial rescue by LCN2 overexpression further links the SP1-LCN2 pathway to ferroptosis-related astrocytic injury under hemorrhagic stress.</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":"51 6","pages":""},"PeriodicalIF":4.5,"publicationDate":"2026-11-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149338247","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":"Electroacupuncture Alleviates Migraine Possibly by Regulating KAT and Inhibiting nNOS Expression via the PGC-1α/PPARα/δ Signaling Pathway","authors":"Hui Zhang,&nbsp;Caiyan He,&nbsp;Minming Shao,&nbsp;Feng Zhang,&nbsp;Jiabi Li,&nbsp;Shengdong He","doi":"10.1007/s11064-026-04941-1","DOIUrl":"10.1007/s11064-026-04941-1","url":null,"abstract":"<div><p>Migraine is a widespread neurological disorder that presents a significant challenge to global health. Electroacupuncture (EA) has been explored as a therapeutic intervention for migraine, but its mechanisms are still poorly understood. Our study aimed to validate the therapeutic efficacy of EA for migraine and explore its underlying mechanism. An acute migraine rat model was established using nitroglycerin (NTG) injection. Mechanical pain thresholds were assessed using von Frey filaments. Histopathological examination was conducted through H&amp;E staining. The expression of CGRP, c-Fos, PGC-1α, PPARα/δ, and KAT was detected by immunohistochemistry. Iba-1 expression was evaluated by immunofluorescence staining. The protein levels were assessed using Western blot, and the mRNA level of KAT was quantified via qRT-PCR. The concentrations of inflammatory cytokines, neuropeptide, and key metabolites were measured by ELISA. EA significantly alleviated the migraine-like symptoms, mechanical hyperalgesia, and pathological alterations caused by NTG. NTG decreased the levels of TRP, L-KYN, and KYNA, which were partially reversed by EA treatment. However, KAT II inhibitors attenuated the effects of EA. Moreover, PGC-1α activators reversed the effects of LPS on the PGC-1α/PPARα/δ signaling pathway, KAT protein expression and the release of inflammatory factor. EA upregulated the expression of PGC-1α, PPARα/δ, and KAT, reduced nNOS, SP, and CGRP levels and restored the content of TRP, L-KYN, and KYNA, which were reversed after PGC-1α inhibitors treatment. Our findings demonstrate that EA may alleviate migraine, at least in part, by regulating KAT and inhibiting nNOS expression associated with the PGC-1α/PPARα/δ signaling pathway.</p></div>","PeriodicalId":719,"journal":{"name":"Neurochemical Research","volume":"51 6","pages":""},"PeriodicalIF":4.5,"publicationDate":"2026-11-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149338131","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":"miR-205-5p Alleviates Thrombin-Induced Injury in Brain Microvascular Endothelial Cells by Directly Targeting PTEN","authors":"Likun Han,&nbsp;Dun Liu,&nbsp;Zhifeng Wu,&nbsp;Hongyu Li,&nbsp;Yunyun Lu","doi":"10.1007/s11064-026-04950-0","DOIUrl":"10.1007/s11064-026-04950-0","url":null,"abstract":"<div><p>Hypertensive intracerebral hemorrhage (HICH) is a severe cerebrovascular disorder with high morbidity and mortality, often presenting significant diagnostic difficulties. Its underlying molecular mechanisms remain unclear. This work investigated the regulatory interplay between miR-205-5p and PTEN in HICH. The expression levels of miR-205-5p and PTEN were detected by qRT-PCR. ROC analysis was employed to assess the prognostic value of miR-205-5p, with logistic regression adopted for factor analysis. Cell viability and apoptosis were detected by MTT assay and flow cytometry. MDA level and SOD activity were measured with corresponding commercial kits. Bioinformatics prediction was performed using miRDB, miRWalk, and TargetScan, followed by dual-luciferase reporter assays to validate target genes. HICH patients exhibited decreased miR-205-5p levels, and this molecule effectively predicted poor prognosis. Its expression showed inverse associations with systolic blood pressure, diastolic blood pressure, and hematoma volume, while it was positively correlated with GCS score. Regression analysis indicated that miR-205-5p was an independent protective factor against poor prognosis, while hemorrhage location and hematoma volume were independent risk factors for poor prognosis. Elevated miR-205-5p alleviated thrombin-triggered cellular injury and oxidative stress. PTEN was verified as a direct target gene of miR-205-5p. The expression level of PTEN was significantly upregulated in HICH patients, and PTEN expression was negatively correlated with miR-205-5p expression. Further functional experiments demonstrated that overexpression of PTEN could reverse the protective effect of elevated miR-205-5p in HCMEC-D3 cells, as evidenced by decreased TEER, increased FITC‑dextran permeability, and reduced tight‑junction protein expression. These findings were further supported by data from HUVECs, although validation in primary brain microvascular endothelial cells or other independent blood–brain barrier models is still warranted. miR-205-5p mitigates cell damage under HICH conditions at least in part by targeting PTEN. However, these findings are based on in vitro experiments, and further in vivo studies are required to validate the therapeutic potential of miR-205-5p.</p></div>","PeriodicalId":719,"journal":{"name":"Neurochemical Research","volume":"51 6","pages":""},"PeriodicalIF":4.5,"publicationDate":"2026-11-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149338246","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":"Niwan Bazhen acupuncture activates CLEC3B-Mediated PI3K/AKT/mTOR signaling pathway to suppress autophagy and exerts neuroprotection against ischemic stroke","authors":"Hong Guo,&nbsp;Keyu Lin,&nbsp;Meng Gong,&nbsp;Di Zhang,&nbsp;Zhipeng Wu,&nbsp;Danqing Luo,&nbsp;Song Jin","doi":"10.1007/s11064-026-04940-2","DOIUrl":"10.1007/s11064-026-04940-2","url":null,"abstract":"<div><p>Ischemic stroke (IS) is one of the leading causes of disability and mortality worldwide. Excessive autophagy triggered by cerebral ischemia exacerbates neuronal apoptosis and necrosis. Acupuncture at Niwan Bazhen (Acu) has unique advantages in stroke rehabilitation, and our previous studies have demonstrated its ability to alleviate neuronal apoptosis after IS. However, the mechanisms underlying its therapeutic effects remain elusive. Transcriptomic microarray expression profiling revealed that C-type lectin domain family 3 member B (CLEC3B) was significantly downregulated in the brain of middle cerebral artery occlusion/reperfusion (MCAO/R) rats, and this downregulation was reversed by Acu. Lentivirus-mediated overexpression of CLEC3B improved neurological function, reduced cerebral infarction, and alleviated cerebral edema in MCAO/R rats, and decreased neuronal apoptosis in the peri-infarct cortex. Western blot analysis demonstrated that CLEC3B overexpression activated the PI3K/AKT/mTOR signaling pathway, reduced the LC3-II/LC3-I ratio, and decreased autophagosome numbers. Conversely, knockdown of CLEC3B nearly abolished the neuroprotective effects of Acu in MCAO/R rats. In vitro, CLEC3B dificiency inhibited the PI3K/AKT/mTOR pathway and impaired autophagic flux in rat cortical neurons under oxygen–glucose deprivation/reoxygenation (OGD/R) conditions. Treatment of OGD/R-exposed rat cortical neurons with recombinant CLEC3B protein or CLEC3B-overexresing lentivirus activated the PI3K/AKT/mTOR pathway and inhibited autophagy, an effect that was abrogated by the PI3K inhibitor LY294002. Collectively, these findings indicate that CLEC3B, as a core target of Acu regulation, exerts neuroprotection against IS by inhibiting excessive neuronal autophagy via activating the PI3K/AKT/mTOR signaling pathway.</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":"51 6","pages":""},"PeriodicalIF":4.5,"publicationDate":"2026-11-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149338129","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":"Rotigotine Attenuates Mechanical Hypersensitivity in 6-OHDA-Lesioned Rats: Associations with D2/D3 Receptors and Spinal Glial NF-κB/p65 Signaling","authors":"Jazmin Santamaria-Anzures,&nbsp;Guadalupe Martínez-Lorenzana,&nbsp;Estefanía González-Morales,&nbsp;Dafne Palmeros-Barreda,&nbsp;Ledy De-la-Cruz-Martínez,&nbsp;Francisco Cortés-Benítez,&nbsp;Julia Pérez-Ramos,&nbsp;Miguel Condés-Lara,&nbsp;Beatriz Godínez-Chaparro","doi":"10.1007/s11064-026-04948-8","DOIUrl":"10.1007/s11064-026-04948-8","url":null,"abstract":"<div><p>Pain is a debilitating non-motor symptom of Parkinson’s disease (PD). This study investigated whether rotigotine attenuated pain hypersensitivity (allodynia and hyperalgesia) in hemiparkinsonian rats and explored D1/D2/D3 receptor involvement, NF-κB/p-p65 signaling modulation in glial cells, and spinal TNF-α and IL-1β expression. The PD model was induced by unilateral 6-OHDA injection into the substantia nigra pars compacta (SNpc). Pain sensitivity was assessed using von Frey filaments. Immunohistochemistry and immunofluorescence were used to analyze tyrosine hydroxylase levels in the SNpc and striatum, GFAP, Iba-1, and NF-κB/p-p65 expression in the dorsal horn of the L5 spinal cord, and ELISA was used to determine TNF-α and IL-1β levels in the lumbar spinal cord. Both acute (8 h) and subacute (5-day) intranasal rotigotine (0.1, 0.5, 0.75, and 1 mg/kg) showed antiallodynic and antihyperalgesic effects. These effects were prevented by selective D2 (L-741,626; 14.6 nmol) and D3 (nafadotride; 3 nmol) receptor antagonists, but not by the D1 receptor antagonist SCH-23,390 (30 nmol). Subacute rotigotine was associated with reduced 6-OHDA-induced glial activation, decreased NF-κB/p-p65 expression, and attenuated spinal TNF-α and IL-1β levels. Molecular docking suggests a potential interaction between rotigotine and the p65 subunit of NF-κB, with favorable binding energy. In conclusion, rotigotine moderated PD-related pain, potentially through D2/D3 receptor activation and modulation of neuroinflammation. This suggested antinociceptive effect may be linked to suppressing glial activation and inhibiting spinal astrocytes’ NF-κB/p-p65 signaling, potentially reducing subsequent proinflammatory cytokine release. These findings suggest that rotigotine may represent a promising therapeutic option for managing sensory hypersensitivity in PD.</p></div>","PeriodicalId":719,"journal":{"name":"Neurochemical Research","volume":"51 6","pages":""},"PeriodicalIF":4.5,"publicationDate":"2026-11-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://link.springer.com/content/pdf/10.1007/s11064-026-04948-8.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149332022","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":"Neurophysiological Mechanisms Underlying the Anticonvulsant Potential of Sarcococca saligna (D.Don) Müll.Arg. in Experimental Epilepsy","authors":"Uzma Saleem,&nbsp;Maryam Farrukh,&nbsp;Warda Iftikhar,&nbsp;Ejaz Basheer,&nbsp;Alia Erum,&nbsp;Farah Javaid","doi":"10.1007/s11064-026-04946-w","DOIUrl":"10.1007/s11064-026-04946-w","url":null,"abstract":"<div><p><i>Sarcococca saligna (S. saligna)</i>, a medicinal plant, has traditionally been used due to its beneficial effects on the nervous system. This study evaluated the anticonvulsant efficacy of <i>S. saligna</i> methanolic extract (SSME) against pentylenetetrazol induced seizures (60 mg/kg) in Wistar rats. Sodium valproate (300 mg/kg, administered orally) served as the reference drug. Rats received SSME at doses of 250, 500, and 1000 mg/kg for seven days. The anticonvulsant potential of SSME was evaluated using neurobehavioral tests and quantifying neurotransmitters and oxidative stress biomarkers. Biochemical and neurochemical tests showed that extract treated rats without seizures showed significant (<i>p</i> &lt; 0.001) restoration of the levels of dopamine (DA), noradrenaline (NA), serotonin, and antioxidant enzymes (SOD, CAT), along with lower levels of malondialdehyde (MDA). Treatment with SSME reinstated these parameters to near normal levels. Furthermore, the extract restored the balance between inhibitory and excitatory neurotransmitters by increasing GABA and maintaining normal glutamate levels in brain homogenates. Histopathological analyses revealed substantial recovery from neuronal degeneration and vacuolization following extract tratment in epileptic rats. The results show that SSME has significant anticonvulsant properties, making it a possible treatment for epilepsy. The findings of current study showed that SSME significantly improved motor function, restored neurotransmitter balance, and maintained antioxidant defenses without producing apparent treatment-related adverse effects under the experimental conditions. These findings suggest that SSME has promise as a potential therapeutic candidate for epilepsy and merits further preclinical and clinical investigation.</p></div>","PeriodicalId":719,"journal":{"name":"Neurochemical Research","volume":"51 6","pages":""},"PeriodicalIF":4.5,"publicationDate":"2026-11-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149316914","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":"Revealing Pharmacological Target for Comorbid Epilepsy in Alzheimer’s Disease: Neurochemical Insights from STZ Mice","authors":"Arvinder Kaur,&nbsp;Rajesh Kumar Goel","doi":"10.1007/s11064-026-04947-9","DOIUrl":"10.1007/s11064-026-04947-9","url":null,"abstract":"<div><p>Despite growing evidences of shared neurochemical alterations linked to comorbid epilepsy in AD, effective unified therapeutic strategies remain lacking. Thus, the present investigation was designed to identify shared neurochemical changes associated with lowered convulsive threshold in STZ (streptozotocin) model of AD-type dementia to pharmacologically address this comorbidity. Swiss albino mice were injected STZ (3 mg/kg, ICV) to induce AD-like pathology. On day 22nd, STZ mice were divided into two groups: one group served as AD control (STZ) and another group (STZ + PTZ) received PTZ (35 mg/kg) kindling to assess the reduced epileptogenesis threshold while naïve served as negative control. One more group was involved as epileptic control (PTZ). All groups underwent behavioral assessment using elevated plus maze, novel object recognition test and radial arm maze. Mice were euthanized on day 48th to collect the brain samples. The brain homogenate was used to assess redox status (GSH, TBARS and ROS), acetylcholinesterase (AChE) activity, amyloid and tau protein expression, histological alterations for specific disease pathology. As well as for neurochemical analysis to assess the shared neurochemical targets associated with comorbid epilepsy in AD. STZ mice were subjected to PTZ kindling exhibited significant greater seizure severity. The kindled status achieved by the sixth injection of PTZ, indicating reduced epileptogenic threshold. Behavioural results indicated significant cognitive impairment in STZ + PTZ treated mice compared with naive mice in EPM, NORT and RAM test. Significantly increased oxidative stress and cholinergic dysfunctions observed in STZ + PTZ mice. Neurochemical analysis revealed augmented excitatory neurotransmitter levels, along with declined glycine, GABA, taurine and arginine in STZ + PTZ mice. Moreover, reduced levels of monoamines and their metabolites reflect cognitive deficits in STZ and STZ + PTZ mice. This increased susceptibility to seizures was accompanied by significantly increased oxidative stress and excitatory neurotransmission in STZ + PTZ mice. Collectively, these observations suggest that AD related neurodegeneration may predispose to epileptogenesis further aggravate neurochemical changes. Our findings suggest that taurine, arginine and monoamines may serve as a shared neurochemical target for comorbid epilepsy in AD-type dementia.</p></div>","PeriodicalId":719,"journal":{"name":"Neurochemical Research","volume":"51 6","pages":""},"PeriodicalIF":4.5,"publicationDate":"2026-10-31","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149316915","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":"Intracerebral Administration of a Novel, Bioactive Peptide Induces a Biochemical Profile in Rat Brain Reminiscent of Alzheimer’s Disease","authors":"Bethany Watkinson,&nbsp;Tobias Bast,&nbsp;Stuart Williams,&nbsp;Karine Bourgade,&nbsp;Sara Garcia-Rates,&nbsp;Sibah Hasan,&nbsp;Susan Greenfield","doi":"10.1007/s11064-026-04944-y","DOIUrl":"10.1007/s11064-026-04944-y","url":null,"abstract":"<div><p>Alzheimer’s disease (AD) presents a great unmet clinical need, but the much needed replication of the characteristic neuropathology in animal models has had limited success. Here, we provide in vivo evidence that T30, a bioactive peptide posited to drive AD, can induce in the rat brain a biochemical profile resembling AD pathology. Bilateral microinfusions of T30 into the medial septum/vertical diagonal band were administered twice a week for three weeks in rats. Although there was no effect on locomotor activity, novel object recognition and watermaze delayed-matching-to-place performance, T30 infusion reduced weight growth in the rats. <i>Post mortem </i>immunohistochemistry showed that T30 increased the AD biomarkers amyloid beta and phosphorylated tau in the cortex, hippocampus, and midbrain. Significant neuronal loss, indicated by reduced NeuN⁺ staining, was observed in brain tissue pooled from neocortex, hippocampus and midbrain. Further analysis showed a strong correlation between the 14mer T14, the active component of T30, and levels of its parent molecule acetylcholinesterase. However, this correlation only applied to protein levels, not enzymatic activity, suggesting independence from cholinergic transmission. Together, these findings support a non-cholinergic, peptide-driven mechanism by which T30 contributes to Alzheimer’s-like neurodegeneration.</p></div>","PeriodicalId":719,"journal":{"name":"Neurochemical Research","volume":"51 6","pages":""},"PeriodicalIF":4.5,"publicationDate":"2026-10-31","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149316912","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":"Therapeutic Potential of Formononetin in Drug-Resistant Epilepsy: Evidence from a Rotenone–PTZ–Lamotrigine Mouse Model","authors":"Nidhi Khedpande,&nbsp;Kalyani Barve","doi":"10.1007/s11064-026-04945-x","DOIUrl":"10.1007/s11064-026-04945-x","url":null,"abstract":"<div><p>Drug-resistant epilepsy (DRE) affects nearly one-third of individuals with epilepsy and remains a major therapeutic challenge despite the availability of multiple antiseizure medications. Mitochondrial dysfunction and chronic neuroinflammation, particularly NLRP3 inflammasome activation, are increasingly recognized as key contributors to pharmacoresistance. Formononetin, a plant-derived isoflavone, has shown anticonvulsant and neuroprotective effects in pentylenetetrazol (PTZ) kindled mice by restoring glutamate–GABA balance and attenuating neuroinflammatory signaling. The present study explored the therapeutic potential of formononetin in a rotenone–PTZ–lamotrigine mouse model of DRE. Mice were subjected to rotenone-adjuvant PTZ kindling in the presence of lamotrigine to induce a refractory seizure phenotype and were subsequently treated with formononetin. Seizure severity was quantified using the Racine scale, and GABA and glutamate levels were measured in whole-brain tissue. Oxidative and inflammasome-related changes were assessed by estimating NAD(P)H: quinone oxidoreductase-1 (NQO1), IL-1β, and caspase-1 in hippocampal and cortical regions using ELISA. We also evaluated astroglial and microglial activation by GFAP and Iba1 expression in the hippocampus and cortex. Formononetin treatment reduced seizure severity, improved the excitatory–inhibitory neurotransmitter balance, enhanced NQO1 levels, and attenuated IL-1β levels and caspase-1 activation, accompanied by a marked reduction in GFAP and Iba1-positive glial reactivity. These findings suggest that formononetin confers anticonvulsant and neuroprotective effects in a mitochondrial dysfunction-linked, lamotrigine-resistant epilepsy model, likely via coordinated modulation of oxidative defense, NLRP3–caspase-1 signaling, and glial activation. Formononetin thus emerges as a promising adjunctive candidate for managing drug-resistant epilepsy, warranting further mechanistic and translational investigation.</p></div>","PeriodicalId":719,"journal":{"name":"Neurochemical Research","volume":"51 6","pages":""},"PeriodicalIF":4.5,"publicationDate":"2026-10-31","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149316916","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}