IBRO Neuroscience Reports最新文献

{"title":"Medullary dorsal horn neurons activated during voluntary diving express neurotransmitter receptors for glutamate and substance P","authors":"P.F. McCulloch,&nbsp;K.M. DiNovo","doi":"10.1016/j.ibneur.2025.12.004","DOIUrl":"10.1016/j.ibneur.2025.12.004","url":null,"abstract":"<div><div>The diving response is a cardiorespiratory reflex characterized by apnea, bradycardia and increased peripheral vascular resistance when animals submerge underwater. Afferent information initiating this reflex response projects from the nasal mucosa via trigeminal nerves to activate second-order afferent neurons within the medullary dorsal horn (MDH). The present study investigated the synapse between these trigeminal nerves and MDH neurons, specifically what neurotransmitter receptors are expressed by MDH neurons activated during diving. Male Sprague-Dawley rats were trained to dive repetitively through an underwater maze, and Fos was used as a measure of neuronal activation. Immunohistochemistry combined with epifluorescent microscopy was used to determine which ionotropic glutamate receptor subunits, or if the Substance P receptor NK-1, were co-expressed by activated MDH neurons. Results indicate repetitive diving primarily activates small oval-shaped MDH neurons, and these Fos-positive MDH neurons co-express AMPA glutamate receptor subunits GluA1 and GluA2/3, KA glutamate receptor subunit GluK5, and NMDA glutamate receptor subunit GluN1. Since these subunits are constituent parts of their respective receptor structure, these findings reveal the formation of AMPA, KA, and NMDA glutamate receptors on the cellular membrane of these activated MDH neurons. In addition, MDH neurons activated by repetitive diving co-express the Substance P receptor NK-1. This research indicates that MDH neurons activated by diving express neurotransmitter receptors for both glutamate and SP. This supports the assertion that trigeminal nerves innervating the nasal passages release glutamate and SP within their central synapses in the brainstem and can function as part of the afferent limb of a cardiorespiratory reflex.</div></div>","PeriodicalId":13195,"journal":{"name":"IBRO Neuroscience Reports","volume":"20 ","pages":"Pages 14-24"},"PeriodicalIF":2.9,"publicationDate":"2026-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145753855","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Potential protective role of soluble fiber in mitigating tinnitus symptoms: A case-control study","authors":"Masoomeh Ataei Kachooei ,&nbsp;Majid Kamali ,&nbsp;Fatemeh Sadat Fahimzad ,&nbsp;Mohammadtaghi Ghorbani Hesari ,&nbsp;Malikeh Mohajerani ,&nbsp;Rezvan Mohammadi ,&nbsp;Abdolrahman Parhiz ,&nbsp;Pegah Samani ,&nbsp;Fatemeh Azaryan ,&nbsp;Sara Khoshdooz ,&nbsp;Maryam Gholamalizadeh ,&nbsp;Bojlul Bahar ,&nbsp;Soheila Shekari ,&nbsp;Akram Kooshki ,&nbsp;Saeid Doaei","doi":"10.1016/j.ibneur.2025.10.002","DOIUrl":"10.1016/j.ibneur.2025.10.002","url":null,"abstract":"<div><h3>Background</h3><div>Tinnitus, the perception of sound without any external source, affects millions of people worldwide and tends to increase with age. Evidence suggested that dietary fiber may play a critical role in mitigating the risk of tinnitus. This study aims to investigate the potential association between dietary fiber intake and the risk of tinnitus.</div></div><div><h3>Methods</h3><div>This cross-sectional study included a total of 300 Iranian women, with 150 stable tinnitus and 150 controls. Dietary intake was assessed using a validated questionnaire and analyzed using Nutritionist IV software. The association of dietary fiber intake and tinnitus was evaluated employing logistic regression analysis.</div></div><div><h3>Results</h3><div>Patients with tinnitus had significantly lower levels of daily soluble fiber intake compared to controls (P &lt; 0.05). The analysis demonstrated a negative association between tinnitus and the daily soluble fiber intake, with an adjusted odds ratio (OR) of 0.71 (95 % CI: 0.51–0.97, P = 0.03). This association remained significant after further adjustment for calorie intake (OR: 0.71, 95 % CI: 0.52–0.98, P = 0.04). No significant association was observed between tinnitus and the intake of total, crude, or insoluble fiber.</div></div><div><h3>Conclusion</h3><div>Our findings indicated that a diet rich in soluble fiber, such as fruits and grains, may help mitigate tinnitus symptoms. Further, longitudinal studies are needed to confirm these findings and explore the potential mechanisms by which dietary fiber impacts tinnitus risk.</div></div>","PeriodicalId":13195,"journal":{"name":"IBRO Neuroscience Reports","volume":"20 ","pages":"Pages 1-4"},"PeriodicalIF":2.9,"publicationDate":"2026-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145753856","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Association between dietary magnesium intake and epilepsy: The mediating role of composite dietary antioxidant index based on a cross-sectional study","authors":"Yali Lai ,&nbsp;Yi Zhou ,&nbsp;Le Yang,&nbsp;Jierong Yin","doi":"10.1016/j.ibneur.2026.02.005","DOIUrl":"10.1016/j.ibneur.2026.02.005","url":null,"abstract":"<div><h3>Background</h3><div>Epilepsy affects 1.2 % of the US population, with one-third of cases being drug-resistant. Magnesium modulates neuronal excitability, and dietary insufficiency may elevate seizure risk. Systemic inflammation, quantified by the Composite Dietary Antioxidant Index (CDAI), represents a plausible mediator, but population-level evidence remains limited.</div></div><div><h3>Objective</h3><div>To investigate associations between dietary magnesium intake and epilepsy prevalence, assess CDAI-mediated pathways, and identify high-benefit subgroups.</div></div><div><h3>Methods</h3><div>Cross-sectional analysis included 33,486 adults (≥20 years) from NHANES 2013–2018. Dietary magnesium intake was derived from two 24-hour recalls and analyzed continuously (per SD) and categorically (quartiles). Epilepsy was self-reported. CDAI integrated six micronutrient intakes. Weighted multivariable logistic regression evaluated magnesium-epilepsy associations, adjusted for sociodemographic, clinical, and dietary covariates. Mediation analysis quantified CDAI’s role.</div></div><div><h3>Results</h3><div>After full adjustment, each SD increase in magnesium intake was associated with 62 % lower epilepsy prevalence (OR = 0.38, 95 % CI: 0.21–0.70, p = 0.004). Quartile analysis revealed a significant inverse trend (p-trend = 0.032), with Q4 (highest intake) exhibiting the lowest risk (OR = 0.38, 95 % CI: 0.12–1.15). CDAI mediated 50.1 % of magnesium’s protective effect (indirect effect: −0.478, 95 % CI: −1.031 to −0.166; p &lt; 0.001). Stronger inverse associations occurred in Non-Hispanic Black (OR = 0.32, 95 % CI: 0.11–0.94) and Mexican American (OR = 0.35, 95 % CI: 0.16–0.76) individuals (p-interaction = 0.009) and those with obesity (OR = 0.26, 95 % CI: 0.10–0.68).</div></div><div><h3>Conclusion</h3><div>Higher dietary magnesium intake is associated with significantly reduced epilepsy prevalence in US adults, with half of this effect mediated by attenuated inflammation (CDAI). Populations with elevated inflammation burdens or socioeconomic disadvantages may derive particular benefit. These findings support magnesium-rich diets as a potential preventive strategy and warrant prospective validation.</div></div>","PeriodicalId":13195,"journal":{"name":"IBRO Neuroscience Reports","volume":"20 ","pages":"Pages 244-251"},"PeriodicalIF":2.9,"publicationDate":"2026-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146170476","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Ondansetron reduces seizures and improves cognitive impairment in a rat model of temporal lobe epilepsy","authors":"Yao Zhang,&nbsp;Ying Sun,&nbsp;Jie Gao,&nbsp;Juan Ni","doi":"10.1016/j.ibneur.2025.12.009","DOIUrl":"10.1016/j.ibneur.2025.12.009","url":null,"abstract":"<div><div>Temporal lobe epilepsy (TLE) remains an intractable chronic neurological disorder. Emerging evidence suggests a crucial modulatory role for the 5-hydroxytryptamine 3 receptor (5-HT₃R) in epilepsy. Ondansetron, a selective 5-HT₃ receptor antagonist widely used as an antiemetic, has demonstrated neuroprotective effects in preclinical models of several neurological disorders. However, its potential therapeutic efficacy in chronic TLE has not yet been investigated. In this study, we evaluated ondansetron’s effects on spontaneous recurrent seizures (SRS), cognitive function, and hippocampal neurodegeneration in a pilocarpine-induced rat model of chronic TLE. Rats received three weeks of intraperitoneal ondansetron, after which spontaneous recurrent seizures (SRS), cognitive performance, and hippocampal neurodegeneration were assessed. Levels of key neurotransmitters (glutamate, GABA), markers of oxidative stress, and inflammatory cytokines were also measured. Ondansetron treatment significantly reduced SRS frequency, improved cognitive function, attenuated hippocampal impairment, and suppressed synaptic remodeling. It also lowered glutamate levels, neuroinflammation, and oxidative stress. The anti‑epileptic and neuroprotective effects of ondansetron in TLE may be attributed to its multi‑faceted properties, including anti‑inflammatory, anti‑oxidative, neurotransmitter‑modulating, and synaptic‑stabilizing properties. These findings highlight ondansetron as a promising candidate for adjunctive therapy in drug‑resistant TLE.</div></div>","PeriodicalId":13195,"journal":{"name":"IBRO Neuroscience Reports","volume":"20 ","pages":"Pages 67-75"},"PeriodicalIF":2.9,"publicationDate":"2026-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145881222","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"DNA Methylation-estimated Phenotypes, Telomere length, Aging and Risk of Intracranial Aneurysms: Evidence from genetic studies","authors":"Xin Zhang MS ,&nbsp;Aierpati Maimaiti MD ,&nbsp;Meixia Xie MD ,&nbsp;Mirzat Turhon MD ,&nbsp;Naibijiang Yalikun MD ,&nbsp;Wenbao Liang MD","doi":"10.1016/j.ibneur.2026.05.009","DOIUrl":"10.1016/j.ibneur.2026.05.009","url":null,"abstract":"<div><h3>Background</h3><div>The risk of intracranial aneurysm (IA) is increased in older population, suggesting a role for aging. To evaluate the association of genetic variants linked to DNA methylation-estimated phenotypes, telomere length, and aging, with the risk of IA by employing two-sample Mendelian randomization.</div></div><div><h3>Methods</h3><div>Sex-specific summary-level outcome data were extracted from the GWAS of IA, including 23 cohorts with a total of 5140 cases and 71934 controls. All the study participants were of European ancestry. To improve validity, five varying Mendelian randomization techniques were used in the analysis (MR-Egger, weighted median, inverse variance weighted, simple mode, and weighted mode).</div></div><div><h3>Results</h3><div>There was a suggestive negative causal relationship between Intrinsic epigenetic age acceleration and unruptured IA (P=0.022, OR=0.906 [95% CI, 0.83-0.99]), though this did not remain significant after multiple testing correction (corrected P threshold=0.00208). No causal effect was observed between any other methylation-estimated phenotype and aSAH or UIA (all P&gt;0.05 after correction). A suggestive causal relationship between longevity and aSAH (P=0.020, OR=1.100 [1.01-1.19]) was observed, with a 9.95% increase in disease risk per 1-SD increase in age, but this also did not withstand multiple testing correction. Each 1-SD increase in telomere length was associated with a 0.9% increase in DNA methylation-estimated granulocyte proportions (P=0.0025, OR=1.009 [1.003-1.015]) and a 55% increase in intrinsic epigenetic age acceleration (P=0.018, OR=1.552 [1.080-1.551]), with the former remaining significant after correction.</div></div><div><h3>Conclusion</h3><div>A negative causal relationship between intrinsic epigenetic age acceleration and IA suggests that an increase in intrinsic apparent age acceleration reduces the risk of IA. The underlying mechanisms and their potential to lower the prevalence of IA as an intervention target require further research.</div></div>","PeriodicalId":13195,"journal":{"name":"IBRO Neuroscience Reports","volume":"21 ","pages":""},"PeriodicalIF":2.9,"publicationDate":"2026-05-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148103860","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Corrigendum to \"Molecular mechanisms governing development of the hindbrain choroid plexus and auditory projection: A validation of the seminal observations of Wilhelm His\" [IBRO Neurosci. Rep. 13 (2022) 306-313].","authors":"Joel C Glover, Bernd Fritzsch","doi":"10.1016/j.ibneur.2022.11.004","DOIUrl":"https://doi.org/10.1016/j.ibneur.2022.11.004","url":null,"abstract":"<p><p>[This corrects the article DOI: 10.1016/j.ibneur.2022.09.011.].</p>","PeriodicalId":13195,"journal":{"name":"IBRO Neuroscience Reports","volume":"19 ","pages":"e1"},"PeriodicalIF":2.9,"publicationDate":"2025-12-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12834030/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146062717","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Corrigendum to \"Acute iron overload aggravates blood-brain barrier disruption and hemorrhagic transformation after transient focal ischemia in rats with hyperglycemia\" [IBRO Neurosci. Rep. 13 (2022) 87-95].","authors":"Qian Wu, Chenchen Wei, Siqi Guo, Junfeng Liu, Hengyi Xiao, Simiao Wu, Bo Wu, Ming Liu","doi":"10.1016/j.ibneur.2022.07.004","DOIUrl":"https://doi.org/10.1016/j.ibneur.2022.07.004","url":null,"abstract":"<p><p>[This corrects the article DOI: 10.1016/j.ibneur.2022.06.006.].</p>","PeriodicalId":13195,"journal":{"name":"IBRO Neuroscience Reports","volume":"19 ","pages":"1174-1175"},"PeriodicalIF":2.9,"publicationDate":"2025-12-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12834014/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146062677","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"The influence of mesenchymal stem cells on the severity of hypoxic-ischemic brain damage in neonatal rats via serum cytokines.","authors":"Sifeng Yue, Feng Lin, Zenghong Huang, Xinyi Liang, Shuchun Lü, Yuan Tan","doi":"10.1016/j.ibneur.2025.12.002","DOIUrl":"10.1016/j.ibneur.2025.12.002","url":null,"abstract":"<p><strong>Background: </strong>Neonatal hypoxic-ischemic brain damage (Hypoxic‑Ischemic Brain Damage, HIBD) is a severe neurological disorder caused by perinatal asphyxia. Its severe long-term sequelae impose a heavy burden on families and society. Therefore, effective early diagnosis and intervention for HIBD are crucial for improving prognosis.</p><p><strong>Objective: </strong>To investigate the correlation between serum levels of interleukin-6 (IL-6), interleukin-18 (IL-18), and tumor necrosis factor-α (TNF-α) and the severity of hypoxic-ischemic brain damage (HIBD) in neonatal SD rats, as well as the effects of mesenchymal stem cells (MSCs) on serum cytokine levels and the repair of HIBD in rats.</p><p><strong>Methods: </strong>250 7-day-old SD rats were selected and a HIBD model was established using the Rice-Vannucci method. The rats were randomly divided into 5 groups: 1) control group; 2) mild HIBD group; 3) severe HIBD group; 4) mild HIBD + MSCs group; 5) severe HIBD + MSCs group. The MSCs intervention group rats were injected with MSCs into the lumbar spine 1 and 8 days after modeling. Longa scores were evaluated at 0, 3, 7, 11, and 15 days after modeling, and serum levels of IL-6, IL-18, and TNF-α were detected. Brain tissue was stained with hematoxylin-eosin (HE) for Longa scoring. The correlation between serum cytokines and the severity of brain injury was analyzed, and the regulatory effect of MSCs intervention on cytokine expression levels and its role in neural injury repair were further explored.</p><p><strong>Results: </strong>(1) The Longa scores and serum levels of IL-6, IL-18, and TNF-α in the mild HIBD group and severe HIBD group were significantly higher than those in the control group at all stages (P < 0.05), and the severe HIBD group had significantly higher levels than the mild HIBD group at all stages (P < 0.05). (2) After treatment, HE staining showed that the brain tissue damage in the mild HIBD group and mild HIBD + MSCs group improved, and the Longa scores and serum levels of IL-6, IL-18, and TNF-α decreased significantly at all time points (D3, D7, D11, D15) after treatment compared to those before treatment (D0). The Longa scores and serum levels of IL-6, IL-18, and TNF-α in the mild HIBD + MSCs group and severe HIBD + MSCs group decreased significantly at each time point (D3, D7, D11, D15) after treatment compared to those before treatment (D0).</p><p><strong>Conclusion: </strong>The serum levels of IL-6, IL-18, and TNF-α in rats are positively correlated with the severity of HIBD and can reflect the degree of brain tissue injury. They can be used for disease assessment; mesenchymal stem cell treatment can significantly reduce the serum levels of IL-6, IL-18, and TNF-α in HIBD rats, alleviate inflammatory responses, improve symptoms, and repair brain injury.</p>","PeriodicalId":13195,"journal":{"name":"IBRO Neuroscience Reports","volume":"19 ","pages":"1045-1052"},"PeriodicalIF":2.9,"publicationDate":"2025-12-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12743414/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145849842","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Levodopa exerts neuroprotective effects by suppressing microglial proinflammatory activation in a rat hemi-Parkinson's disease model.","authors":"Noriyuki Miyaue, Mohammed E Choudhury, Ikuko Takeda, Junya Tanaka, Ayane Takenaga, Haruto Yamamoto, Yuki Nishikawa, Naoki Abe, Masahiro Nagai, Tasuku Nishihara","doi":"10.1016/j.ibneur.2025.12.001","DOIUrl":"10.1016/j.ibneur.2025.12.001","url":null,"abstract":"<p><p>Levodopa is a central medicine used for the treatment of Parkinson's disease (PD) as a dopamine (DA) precursor that increases DA levels in the striatum. Microglia, resident macrophages in the brain, become activated in response to the progressive degeneration of nigral dopaminergic neurons in PD pathology, while releasing proinflammatory mediators that are harmful to dopaminergic neurons. DA has been shown to prevent proinflammatory activation of microglia. This study showed that DA decreases lipopolysaccharide-induced proinflammatory reactions and increases tissue repairing factors of microglia in cultured rat microglia. Levodopa was administered to 6-hydroxydopmaine (6-OHDA)-induced PD model rats for 7 days, and motor deficits were evaluated after a two-week withdrawal period. The levodopa-treated PD model rats showed a better motor function than the vehicle-treated rats. The administration of levodopa for 7 days led to an increase in DA levels and a suppression of microglial activation in the striatum, which was maintained, even at two weeks after withdrawal. These results suggest that levodopa may act in the PD brain, not only as a DA precursor, but also as an immunosuppressant to reduce neuroinflammation accompanied by PD pathology.</p>","PeriodicalId":13195,"journal":{"name":"IBRO Neuroscience Reports","volume":"19 ","pages":"1053-1062"},"PeriodicalIF":2.9,"publicationDate":"2025-12-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12753262/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145878297","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Chronic fluoxetine modulates perineuronal nets and inhibitory neuronal function in relation to behavioral outcomes","authors":"Hiroshi Ueno ,&nbsp;Eriko Kitano ,&nbsp;Sachiko Mori ,&nbsp;Yu Takahashi ,&nbsp;Shinji Murakami ,&nbsp;Kenta Wani ,&nbsp;Yosuke Matsumoto ,&nbsp;Motoi Okamoto ,&nbsp;Takeshi Ishihara","doi":"10.1016/j.ibneur.2025.10.012","DOIUrl":"10.1016/j.ibneur.2025.10.012","url":null,"abstract":"<div><div>Chronic fluoxetine administration has been reported to enhance neural plasticity in the adult brain, but the underlying structural correlates remain incompletely understood. In particular, the impact of fluoxetine on aggrecan-positive perineuronal nets (PNNs)—critical regulators of plasticity—is largely unknown. We investigated whether chronic fluoxetine treatment (20 mg/kg/day, i.p., 21 days) alters behavior and PNN expression in adult male C57BL/6 N mice. Behavioral assessments included grip strength, hot plate, light/dark transition, elevated plus-maze, open field, Y-maze, social interaction, tail suspension, Porsolt forced swim, and passive avoidance tests. To evaluate structural plasticity, we performed immunohistochemical analyses of parvalbumin (PV)-positive neurons and PNNs using aggrecan-specific antibodies (Cat-315, AB1031) in the primary somatosensory cortex and hippocampus. Fluoxetine-treated mice exhibited increased exploration and reduced anxiety-like behavior in light/dark transition and elevated plus-maze tests, with no significant changes in grip strength or nociception. They also showed increased locomotor activity (distance and entries) in the Y-maze, but did not significantly alter spontaneous alternation performance, and increased social interaction, the latter possibly reflecting abnormal social behavior. No significant differences were observed in depression-like behavior as assessed by tail suspension and forced swim tests. Passive avoidance performance was impaired, suggesting a decline in cognitive function. Immunohistochemical analysis revealed a significant reduction in aggrecan-positive PNN density, particularly in layer 4 of the primary somatosensory cortex and in the CA1 and CA3 regions of the hippocampus. Our results indicate that chronic fluoxetine administration induces behavioral and structural changes indicative of reactivated neuroplasticity. Importantly, these changes are associated with a region- and layer-specific reduction of aggrecan-positive PNNs, underscoring their critical role in modulating adult cortical plasticity.</div></div>","PeriodicalId":13195,"journal":{"name":"IBRO Neuroscience Reports","volume":"19 ","pages":"Pages 781-791"},"PeriodicalIF":2.9,"publicationDate":"2025-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145415819","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}