Neurochemistry international最新文献

{"title":"Assessing effects of microwave electromagnetic field in APP/PS1 mice by in vivo GABA-weighted imaging via variable delay multipulse-chemical exchange saturation transfer MRI","authors":"Siqi Liu ,&nbsp;Yan Cheng ,&nbsp;Xiaolei Zhang ,&nbsp;Yuanyu Shen ,&nbsp;Shuohua Wu ,&nbsp;Yue Chen ,&nbsp;Dafa Shi ,&nbsp;Caiyu Zhuang ,&nbsp;Beibei Chen ,&nbsp;Yazhi Zhong ,&nbsp;Xinxin Wang ,&nbsp;Yaqi Wen ,&nbsp;Xinhui Zheng ,&nbsp;Yanlong Jia ,&nbsp;Jitian Guan ,&nbsp;Gen Yan ,&nbsp;Renhua Wu","doi":"10.1016/j.neuint.2026.106131","DOIUrl":"10.1016/j.neuint.2026.106131","url":null,"abstract":"<div><div>Electromagnetic fields (EMFs) have been shown to be beneficial in treating Alzheimer's disease (AD), but the underlying neurophysiological mechanisms remain unclear. It has been proposed that EMF promotes GABAergic neurogenesis and that abnormal GABA levels are an important influence on the progression of AD. To achieve in vivo GABA-weighted imaging in the brain in APP/PS1 mice, we utilized variable delay multi-pulse (VDMP)-chemical exchange saturation transfer (CEST)- magnetic resonance imaging (MRI) and pathological validation to measure GABA levels in APP/PS1 mice under microwave EMF and explore the therapeutic mechanism. The APP/PS1 mice received a 4-week microwave EMF treatment. The findings show that microwave EMF stimulation significantly increased GABA-weighted signals on MRI of APP/PS1 mouse hippocampus. VDMP-CEST was sensitive in detecting GABA-weighted signals. ELISA showed that microwave EMF stimulation elevated GABA levels in the hippocampus. Compared to in vitro levels, VDMP-CEST accurately detected GABA-weighted signal changes. With the pathological validations, we found that microwave EMF exposure can elevate hippocampal GABA levels by promoting AQP4 polarizion, reducing Aβ accumulation and neuronal degeneration, improving cognitive impairment, and may have slowed AD progression. Collectively, microwave EMF treatment could increase GABA-related changes, which corresponded to the accumulation of Aβ and improvement in the water maze. VDMP-CEST detected levels are highly consistent with pathological evidence, implying that VDMP-CEST is an effective modality for in vivo GABA-weighted imaging during microwave EMF treatment, providing more objective imaging-based diagnostic evidence for monitoring GABA-related pathological changes in AD.</div></div>","PeriodicalId":398,"journal":{"name":"Neurochemistry international","volume":"194 ","pages":"Article 106131"},"PeriodicalIF":4.0,"publicationDate":"2026-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146225076","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":"Comparative neurochemical and neuroprotective effects of lauric acid, ribose-cysteine, and levodopa in an α-synuclein Drosophila model of Parkinson's disease","authors":"Olumayowa Kolawole Idowu ,&nbsp;Ademola Ayodele Oremosu ,&nbsp;Olufunke Olubusola Dosumu","doi":"10.1016/j.neuint.2026.106135","DOIUrl":"10.1016/j.neuint.2026.106135","url":null,"abstract":"<div><div>Parkinson's disease (PD) entails dopaminergic neuronal loss in a gradual manner, which is typically linked to oxidative stress, neuroinflammation, and the neurotransmitter homeostasis disruption. This research compares the neurochemical and neuroprotective impacts of lauric acid (LA), ribose-cysteine (RC), and levodopa (LD) in a transgenic <em>Drosophila melanogaster</em> model where human α-synuclein (α-syn) was expressed in dopaminergic neurons. The transgenic flies received treatment with LA, RC, or LD (250 mg/kg diet) for three weeks and were then evaluated by behavioral assays in conjunction with biochemical and molecular analyses of redox status, inflammatory and apoptotic signaling, neurotransmitter levels, and dopaminergic gene expression. Expression of α-syn caused significant deficiencies of locomotor behavior, oxidative damage, activation of neuroinflammation, changes of dopamine, GABA, and glutamate levels, and reduction of dopa decarboxylase expression. All interventions led to substantial increments in behavioral outcomes and oxidative stress status when compared to untreated PD flies. Out of the three treatments, the RC-induced effects on total antioxidant capacity and cell viability were most notable, along with reduction of lipid peroxidation, TNF-α, and caspase-3 activity. LD was the best at restoring locomotor performance and dopamine levels, whereas LA and RC were more potent at apoptotic signaling reduction and dopaminergic gene expression enhancement. Overall, RC effected broader neurochemical modulation than LA across most parameters. The results from this study suggest that LA, RC, and LD have different yet complementary neuroprotective effects in α-<em>syn</em>-induced neurotoxicity and that RC is particularly effective in modulating oxidative and inflammatory pathways that are involved in PD pathophysiology.</div></div>","PeriodicalId":398,"journal":{"name":"Neurochemistry international","volume":"194 ","pages":"Article 106135"},"PeriodicalIF":4.0,"publicationDate":"2026-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147300703","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":"ERK-dependent astrocytic PAI-1 induction by influenza A virus disrupts the neurochemical balance of the PAI-1/tPA axis","authors":"Eun-Sook Park ,&nbsp;Bo-Bae Park ,&nbsp;Ryeong-Eun Kim ,&nbsp;Yoonseo Hong ,&nbsp;Kyoung Ja Kwon ,&nbsp;Chan Young Shin","doi":"10.1016/j.neuint.2026.106122","DOIUrl":"10.1016/j.neuint.2026.106122","url":null,"abstract":"<div><h3>Background</h3><div>Influenza A virus (IAV), although primarily a respiratory pathogen, is increasingly recognized to affect central nervous system (CNS) function. Astrocytes are key regulators of neurochemical homeostasis and neuroinflammation, but the molecular pathways underlying their response to IAV remain incompletely defined.</div></div><div><h3>Methods</h3><div>Primary rat astrocytes were infected with wild-type IAV (PR8, H1N1) or PB1–F2–deficient IAV (PB1–F2[−]). Regulation of the plasminogen activator inhibitor-1 (PAI-1)/tissue-type plasminogen activator (tPA) system was examined by qPCR, Western blotting, zymography, and ELISA. ERK pathway activation was assessed using phospho-specific antibodies, and pathway dependency was tested using the ERK inhibitor U0126. Functional consequences on neurons were evaluated by neurite outgrowth assays using astrocyte-conditioned medium (ACM).</div></div><div><h3>Results</h3><div>IAV infection induced a robust increase in astrocytic PAI-1 expression and a marked reduction in tPA activity, accompanied by selective activation of ERK signaling. Pharmacological ERK inhibition completely abolished PAI-1 upregulation, indicating that ERK is required for this neurochemical shift. PB1–F2 deletion did not alter PAI-1 induction but partially modified cytokine expression profiles, demonstrating PB1–F2–independent regulation of the PAI-1/tPA axis. Compared with lipopolysaccharide (LPS), IAV elicited substantially lower cytokine levels yet induced markedly higher PAI-1 expression, suggesting a sustained antifibrinolytic phenotype. Neurons exposed to ACM from IAV-infected astrocytes exhibited reduced neurite extension and branching, indicating impaired neuronal structural development through paracrine mechanisms.</div></div><div><h3>Conclusions</h3><div>IAV triggers an ERK-dependent induction of PAI-1 in astrocytes, leading to suppression of tPA activity and disruption of neuronal outgrowth. These findings identify a neurochemical mechanism linking astrocyte-specific MAPK signaling to neuroinflammatory and antifibrinolytic dysfunction during viral infection.</div></div>","PeriodicalId":398,"journal":{"name":"Neurochemistry international","volume":"194 ","pages":"Article 106122"},"PeriodicalIF":4.0,"publicationDate":"2026-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146117341","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":"Involvement of α7 nicotinic acetylcholine receptor-signaling in social behavior impairments in the stressed mice","authors":"Mizuki Uchida ,&nbsp;Masaki Kano ,&nbsp;Norio Ozaki ,&nbsp;Akira Yoshimi ,&nbsp;Yukihiro Noda","doi":"10.1016/j.neuint.2026.106121","DOIUrl":"10.1016/j.neuint.2026.106121","url":null,"abstract":"<div><div>Smoking is considered a form of self-medication for psychosis, including nicotine (NIC) dependence, through stimulation of the nicotinic acetylcholine receptors (nAChRs) in the central nervous system of patients with psychiatric disorders. However, the effects of NIC on neuropsychological functions and the underlying molecular mechanisms remain unclear. We investigated the effects of (−)-NIC on emotional behaviors, expression of intracerebral nAChR subunits, and morphological changes in swim-stressed mice. Stressed mice showed social behavior impairments, low phosphorylation levels of Akt, CaMKII, and ERK, and reduced thickness of the pyramidal neuronal layer in the hippocampus. Acute or repeated administration of (−)-NIC (0.3 mg/kg, s.c.) to stressed mice attenuated social behavior impairments. Repeated administration of PHA568487, a selective α7 nAChR agonist, also attenuated these impairments. The attenuating effects of (−)-NIC were blocked by a selective α7 nAChR antagonist, but not by a selective α4β2 nAChR antagonist. Repeated administration of (−)-NIC ameliorated the reduced phosphorylation levels of Akt, CaMKII, and ERK, as well as morphological abnormalities in the hippocampus, without inducing conditioned place preference. Acute administration of (−)-NIC ameliorated the decreased Akt phosphorylation without affecting morphological abnormalities. Our findings suggest that hippocampal α7 nAChR signal pathways play an important role in social behavior impairments in stressed mice, and that abnormal neuronal morphology via these pathways contributes to the development of such impairments. Activation of α7 nAChRs was identified as a key target for new treatment strategies for emotional impairments in stress-related disorders.</div></div>","PeriodicalId":398,"journal":{"name":"Neurochemistry international","volume":"193 ","pages":"Article 106121"},"PeriodicalIF":4.0,"publicationDate":"2026-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146017056","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":"Receptor tyrosine kinases in Alzheimer's disease: Mechanistic insights and therapeutic implications","authors":"Pengyu Zhao ,&nbsp;Zelin Cao ,&nbsp;Wioletta Rozpędek-Kamińska","doi":"10.1016/j.neuint.2026.106117","DOIUrl":"10.1016/j.neuint.2026.106117","url":null,"abstract":"<div><div>Alzheimer's disease (AD) is a complex neurodegenerative disorder whose pathogenesis remains incompletely understood. It is considered one of the most costly, fatal, and socially burdensome diseases of the twenty-first century. Previous studies have shown that receptor tyrosine kinases (RTKs) play an important role in the pathological progression of AD. RTKs regulate amyloid-beta (Aβ) deposition and Tau hyperphosphorylation, thereby influencing neuronal survival, synaptic plasticity, and spatial cognitive function in patients with AD. From a therapeutic perspective, RTK-targeted interventions offer new avenues for AD treatment. Inhibiting specific RTKs can reduce Aβ production and pathological Tau phosphorylation, thereby slowing disease progression. Conversely, activating selected neuroprotective RTKs can promote neuronal survival, restore synaptic function, and ameliorate cognitive impairment. Several small-molecule inhibitors and monoclonal antibodies targeting RTKs have already demonstrated promising therapeutic potential in preclinical studies. Overall, this review systematically summarizes the clinical features and mechanisms of AD, as well as the current applications and future challenges of RTK-based research in neurodegenerative diseases, providing theoretical guidance for the development and repurposing of novel multi-pathway RTK-directed therapies.</div></div>","PeriodicalId":398,"journal":{"name":"Neurochemistry international","volume":"193 ","pages":"Article 106117"},"PeriodicalIF":4.0,"publicationDate":"2026-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145948326","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":"Short-term infusion of GDF11 after SCI attenuates pericytes loss and BSCB damage to promote recovery of spinal cord function","authors":"Honghao Shen ,&nbsp;Jiangtao Liu ,&nbsp;Minghao Du ,&nbsp;Geng Qin ,&nbsp;Jiani Li ,&nbsp;Yichen Lu ,&nbsp;Hongqian Gao","doi":"10.1016/j.neuint.2026.106124","DOIUrl":"10.1016/j.neuint.2026.106124","url":null,"abstract":"<div><div>To investigate the role of GDF11 in acute neural trauma, this study focused on the effects of GDF11 on pericytes and the blood-spinal cord barrier (BSCB) following spinal cord injury (SCI). We established a mouse SCI model and administered GDF11 infusion for three consecutive days. Spinal cord samples were collected early after injury, and the integrity of the BSCB was evaluated using pathomorphological analysis, Western blotting, immunofluorescence, and transmission electron microscopy. The results demonstrated that GDF11 infusion significantly reduced BSCB damage at 7 days post-SCI, as evidenced by improved intercellular junction integrity and enhanced pericyte coverage. Since neurovascular communication is a critical function of the BSCB, we further assessed neuronal survival and myelin sheath integrity across different groups. In addition, we isolated primary central nervous system microvascular pericytes and simulated SCI through oxygen-glucose deprivation (OGD) culture, with and without GDF11 treatment and its critical receptor TGF-β receptor (TGFR) antagonist, ACE-536. The viability and migration ability of pericytes in each group were evaluated by flow cytometry and migration assays. We found that the GDF11/TGFR/SMAD3 signaling pathway mediates the beneficial effects of GDF11 on SCI. As functional recovery is a key measure of clinical outcome following SCI, behavioral assessments were performed at later stages. Our results showed that early GDF11 infusion significantly improved functional recovery, as demonstrated by enhanced gait performance and increased swimming scores. In conclusion, early post-SCI GDF11 infusion targeting pericytes to regulate BSCB integrity may offer a promising therapeutic approach for SCI recovery.</div></div>","PeriodicalId":398,"journal":{"name":"Neurochemistry international","volume":"193 ","pages":"Article 106124"},"PeriodicalIF":4.0,"publicationDate":"2026-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146123154","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":"Sanguinarine alleviates pendimethalin-induced neurotoxicity via regulating microglial and neuroinflammatory pathways: An interplay of oxidative stress, apoptosis and microglial polarization","authors":"Kang Zhang ,&nbsp;Kiran Amir ,&nbsp;Arifa Mehreen ,&nbsp;Mahmoud El Safadi ,&nbsp;Saadiya Zia ,&nbsp;Salim Jamil ,&nbsp;Ahmed Al-Emam ,&nbsp;Hesham M. Hassan","doi":"10.1016/j.neuint.2026.106119","DOIUrl":"10.1016/j.neuint.2026.106119","url":null,"abstract":"<div><div>Pendimethalin (PMN) is a potent agrochemical that has shown severe neural alterations. Sanguinarine (SAN) is a naturally derived alkaloid that exhibits a wide range of biological properties. The current research was conducted to explore the palliative potential of SAN against PMN-induced neurotoxicity. Thirty-two Sprague Dawley rats were divided into the control, PMN (125 mg/kg), PMN (125 mg/kg) + SAN (15 mg/kg), and SAN (15 mg/kg) alone treated group. PMN intoxication upregulated the mRNA expressions of Aif1 (iba1), cd68, TNF-α, IL-10, IL-6, IL-1β, Nos2, Arg1, and Trem2 while inhibiting the mRNA expression of Tmem119. Neural tissues showed altered redox state after PMN exposure as evidenced by escalated levels of ROS and MDA coupled with marked declined in the activities of HO-1, GPx, CAT, GSR, SOD, and GST. Additionally, PMN administration provoked a sharp decline in the levels of NGF, BDNF, GDNF, Synaptophysin, and PSD-95. Moreover, exposure of PMN elevated the levels of Caspase-9, Bax, and Caspase-3 coupled with a significant reduction in the levels of Bcl-2. Neural tissues showed severe morphological alterations including vacuolar degeneration, neuronal loss, microglial activation, apoptotic bodies, capillary congestion, perineuronal vacuolation, and neural edema after PMN intoxication. Importantly, SAN supplementation notably alleviated neural damage via suppressing the activation of microglial and inflammatory pathways along with regulating redox profile, apoptotic indices, and histopathological alterations. Our in-silico assessment showed excellent binding affinity of SAN with key regulatory proteins thereby suggesting its critical role in suppressing the activation of microglial cells.</div></div>","PeriodicalId":398,"journal":{"name":"Neurochemistry international","volume":"193 ","pages":"Article 106119"},"PeriodicalIF":4.0,"publicationDate":"2026-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145997056","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":"24-Hydroxycholesterol suppresses steroid 5α-reductase-catalyzed conversion in human glioblastoma cell lines: A novel link between brain cholesterol homeostasis and androgen metabolism","authors":"Kjell Wikvall ,&nbsp;Frida Olsson ,&nbsp;Erik Wåhlén ,&nbsp;Ananya Roy ,&nbsp;S.J.Kumari A. Ubhayasekera ,&nbsp;Jonas Bergquist ,&nbsp;Maria Norlin","doi":"10.1016/j.neuint.2026.106116","DOIUrl":"10.1016/j.neuint.2026.106116","url":null,"abstract":"<div><div>Glioblastoma is the most aggressive primary brain tumor in adults. Androgens are reported to influence the development of glioblastoma. Dihydrotestosterone (DHT) is formed from testosterone by action of the enzyme steroid 5α-reductase and is the most potent growth-inducing androgen metabolite.</div><div>24-Hydroxycholesterol, another steroid in the brain, is pivotal for brain cholesterol homeostasis and has been suggested to influence glioblastoma cells. However, a connection between 24-hydroxycholesterol and androgen metabolism related to glioblastoma has not previously been reported. The present study reports that human T98G glioblastoma cells metabolize testosterone into DHT, 3α-androstanediol and androstenedione. The 5α-reductase pathway converted testosterone to DHT and further to 3α-androstanediol. The 17β-hydroxysteroid dehydrogenase pathway metabolized testosterone to androstenedione. Results indicated that the 5α-reductase pathway is the major pathway for testosterone metabolism in this cell line. 24-Hydroxycholesterol significantly suppressed the conversion of testosterone to DHT and 3α-androstanediol, to a similar degree as the synthetic 5α-reductase inhibitor finasteride. Suppression of DHT formation resulted in increased metabolism to androstenedione. Similar effects on DHT formation were observed with the LXR agonist T0901317 as with 24-hydroxycholesterol. In addition, 24-hydroxycholesterol suppressed DHT formation in patient-derived primary GB cell lines U3009 and U3013, indicating that the observed connection between 24-hydroxycholesterol and androgen metabolism is not unique for T98G cells. Furthermore, 24-hydroxycholesterol-mediated suppression of DHT formation was also observed in human neuroblastoma SH-SY5Y cells.</div><div>To summarize, the present data provide information on androgen metabolism in glioblastoma cells and indicate a previously unknown link between cholesterol homeostasis and growth-inducing androgens in glioblastoma and potentially other cell types.</div></div>","PeriodicalId":398,"journal":{"name":"Neurochemistry international","volume":"193 ","pages":"Article 106116"},"PeriodicalIF":4.0,"publicationDate":"2026-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145931676","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":"Blood extracellular vesicles contribute to the exercise-mediated suppression of brain Aβ pathology in the AppNL-G-F knockin mouse model of Alzheimer's disease","authors":"Akiko Takeda ,&nbsp;Toshihide Takeuchi ,&nbsp;Eiko N. Minakawa ,&nbsp;Noriko Tanaka ,&nbsp;Hideki Mochizuki ,&nbsp;Yoshitaka Nagai","doi":"10.1016/j.neuint.2026.106120","DOIUrl":"10.1016/j.neuint.2026.106120","url":null,"abstract":"<div><div>Epidemiological, clinical, and experimental evidence suggest that physical exercise suppresses the deposition of amyloid β (Aβ) plaques in the brain and reduces the risk of Alzheimer's disease (AD). However, how exercise provides such beneficial effects on AD remains largely unclear. In this study, we show that the exercise-mediated suppression of Aβ deposition requires blood extracellular vesicles (EVs) that are upregulated by exercise. We demonstrated that treadmill exercise induces a transient increase in the secretion of blood EVs in both wild-type mice and the <em>App</em>^{<em>NL-G-F</em>} knockin mouse model of AD. Comprehensive analysis of protein contents of the exercise-induced blood EVs demonstrated that molecular chaperones, such as heat shock proteins and cochaperones, are substantially increased, together with substantial changes in proteomic profiles after exercise. Importantly, long-term exercise led to the suppression of Aβ plaque deposition in <em>App</em>^{<em>NL-G-F</em>} knockin mice, but this suppressive effect was almost completely diminished by the pharmacological inhibition of EV secretion. These results indicate that the secretion of blood EVs is increased by exercise, which contributes to the suppression of Aβ pathology in the brain. Our study identifies blood EVs as a key mediator of the benefits of exercise throughout the body including the brain, highlighting the therapeutic potential of exercise-induced EVs for the treatment of AD pathology.</div></div>","PeriodicalId":398,"journal":{"name":"Neurochemistry international","volume":"193 ","pages":"Article 106120"},"PeriodicalIF":4.0,"publicationDate":"2026-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145997062","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":"Swertisin improves Alzheimer's disease-like pathology in 5XFAD male mice through regulation in plasmin activity","authors":"Somin Moon ,&nbsp;Huiyoung Kwon ,&nbsp;Eunbi Cho ,&nbsp;Seungheon Lee ,&nbsp;Se Jin Park ,&nbsp;Minho Moon ,&nbsp;Jong Hoon Ryu ,&nbsp;Dae Sik Jang ,&nbsp;Ho Jung Bae ,&nbsp;Dong Hyun Kim","doi":"10.1016/j.neuint.2026.106118","DOIUrl":"10.1016/j.neuint.2026.106118","url":null,"abstract":"<div><div>Abnormal accumulation of amyloid β (Aβ), which may result from excessive production or impaired clearance, is one of the pathomechanisms of Alzheimer's disease (AD). <u>Plasmin is one of the important proteases involved in the Aβ clearance system</u>. In this study, we investigated whether swertisin can regulate plasmin activity and reduce Aβ pathology. First, we examined whether swertisin regulated plasmin activity, mature brain-derived neurotrophic factor (mBDNF) levels, and plasminogen activator inhibitor-1 (PAI-1) activity in vitro. Next, we assessed the effect of swertisin on memory impairments in an Aβ-injected AD-like mouse model and in 5XFAD mice. To evaluate the involvement of plasmin in the effect of swertisin in the Aβ-injected AD-like mouse model, we used 6-aminocaproic acid (6-AA), a plasmin inhibitor. Additionally, we measured plasmin activity and mBDNF levels in the hippocampus of Aβ-injected AD-like mice and 5XFAD mice. Swertisin increased plasmin activity and mBDNF levels in hippocampal slices from both normal and 5XFAD mice. Moreover, swertisin ameliorated Aβ-induced synaptic long-term potentiation (LTP) deficits in hippocampal slices. Swertisin also mitigated memory impairments induced by ventricular injection of Aβ, and this effect was blocked by 6-AA. Furthermore, swertisin improved learning and memory in 5XFAD mice while reducing Aβ deposition and neuroinflammation. This study demonstrates that swertisin ameliorates AD-like pathology by regulating plasmin activity. Plasmin activated by swertisin may cleave Aβ aggregates and increase mBDNF levels, thereby protecting the brain from Aβ toxicity. Swertisin may represent an effective therapeutic strategy for AD patients.</div></div>","PeriodicalId":398,"journal":{"name":"Neurochemistry international","volume":"193 ","pages":"Article 106118"},"PeriodicalIF":4.0,"publicationDate":"2026-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145951095","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}