Neurochemical Research最新文献

{"title":"Brivaracetam and Topiramate Co-Therapy Attenuates Seizure Progression, Neuroinflammation, and Hippocampal Pathology in Chronic Pentylenetetrazole-Kindled Mice","authors":"Khaled Ahmed Saghir,&nbsp;Zohabia Rehman,&nbsp;Nosheen Malik,&nbsp;Waseem Ashraf,&nbsp;Syed Muhammad Muneeb Anjum,&nbsp;Rana Muhammad Zahid Mushtaq,&nbsp;Faleh Alqahtani,&nbsp;Imran Imran","doi":"10.1007/s11064-025-04571-z","DOIUrl":"10.1007/s11064-025-04571-z","url":null,"abstract":"<div><p>Rational polytherapy is increasingly gaining attention when monotherapy fails to control seizures. Accordingly, the current study investigated the effects of topiramate and brivaracetam, administered individually (10 mg/kg each) or combined, on seizure progression alongside electroencephalographic (EEG) changes and neuroinflammatory responses in Pentylenetetrazole (PTZ)-induced kindled mice. Eleven doses of PTZ (40 mg/kg) were administered on alternate days over three weeks. Monotherapy with topiramate and brivaracetam delayed the development of generalized tonic-clonic seizures during the first week. However, it did not prevent seizures later, resulting in 80% and 60% kindled mice with 25% and 16.16% mortality, respectively. Combination therapy demonstrated 100% protection against kindling progression, with no mortality. EEG recordings revealed progressively increasing epileptiform spikes in PTZ and monotherapy-treated groups throughout the kindling period. Conversely, the combination-treated group exhibited significantly consistent reduction in epileptiform spike activity across all EEG sessions, indicating a better anticonvulsant effect. Post-kindling brain analysis revealed elevated levels of neuroinflammatory markers in the monotherapy-treated groups, while these markers were absent in the combination-treated group. RT-PCR confirmed substantial downregulation of proinflammatory and excitatory markers, including BDNF, TrkB, and TNF-α, indicating suppression of neuroinflammation and excitotoxicity in combination-treated group. Histopathological examination showed neuronal damage in the hippocampal tissues of monotherapy-treated mice, whereas no neuronal degenerations were seen in the brains of combination-treated mice. The results indicate that dual therapy with topiramate and brivaracetam provides superior neuroprotection by modulating neuroinflammatory pathways, thereby preventing seizure development and ictogenesis. These findings support the potential clinical utility of rational polytherapy in drug-resistant epilepsy.</p><h3>Graphical Abstract</h3><p>The figure was generated with https://www.biorender.com (LA28FJGRRL; Dated June 25, 2025).</p><div><figure><div><div><picture><source><img></source></picture></div></div></figure></div></div>","PeriodicalId":719,"journal":{"name":"Neurochemical Research","volume":"50 5","pages":""},"PeriodicalIF":3.8,"publicationDate":"2025-10-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145210797","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":"The Mitochondrial-Astrocyte-Neuron Triad Hypothesis in Parkinson’s Disease: A Toxic Feedback Loop of Metabolism, Aggregation, and Oxidative Stress","authors":"Vaishali Walecha,&nbsp;Pratibha M. Luthra","doi":"10.1007/s11064-025-04559-9","DOIUrl":"10.1007/s11064-025-04559-9","url":null,"abstract":"<div><p>The medical field has spent many years investigating Parkinson's disease (PD), primarily focusing on its main pathogenic feature, dopaminergic neuronal degeneration. Recent studies indicate that PD develops through a complex pathogenic model that links mitochondria to astrocytes and neurons, creating a destructive metabolic loop, a protein aggregation cycle, and oxidative stress. This review examines how mitochondria integrate with astrocytes and neurons in the “triad hypothesis,” offering a multifaceted perspective on PD progression. Despite being previously overlooked, we have observed that astrocytic mitochondria play a central role in maintaining neuroprotection and homeostasis. Given that, dysfunctional mitochondria in astrocytes and neurons lead to metabolic failure, compromised glutamate regulation, while also enhancing α-synuclein aggregation, amplifying neuroinflammation, ferroptotic vulnerability and oxidative stress. Henceforth, this report discusses current insights into astrocyte–neuron metabolic coupling, mitochondrial quality control, and lipid redox imbalance, highlighting the role of astrocytic mitochondria as a strong therapeutic strategy. We discuss experimental and translational approaches that aim to restore triad integrity, including mitophagy enhancement, metabolic reprogramming, mitochondrial transfer, and astrocyte-to-neuron reprogramming. By positioning astrocytic mitochondria at the core of PD pathogenesis, this review advocates novel interventions focused on glial metabolic resilience. This integrated approach addresses three major pathogenic axes. It offers promising potential for disease modification and developing effective therapeutics beyond symptomatic dopamine replacement to correct neurodegenerative conditions.</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 5","pages":""},"PeriodicalIF":3.8,"publicationDate":"2025-10-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145210798","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":"p75NTR Modulation by LM11A-31 Counteracts Oxidative Stress and Cholesterol Dysmetabolism in a Rotenone-Induced Cell Model of Parkinson’s Disease","authors":"Daniele Pensabene,&nbsp;Noemi Martella,&nbsp;Giuseppe Scavo,&nbsp;Emanuele Bisesto,&nbsp;Francesca Cavicchia,&nbsp;Mayra Colardo,&nbsp;Michela Varone,&nbsp;Sandra Moreno,&nbsp;Marco Segatto","doi":"10.1007/s11064-025-04569-7","DOIUrl":"10.1007/s11064-025-04569-7","url":null,"abstract":"<div><p>The p75 neurotrophin receptor (p75NTR) plays a dual role in regulating both pro-survival and pro-apoptotic cascades in various physiological and pathological conditions, including within dopaminergic neuronal population. Notably, its overexpression has been documented in post-mortem Parkinson’s disease (PD) brains, where it correlates with a significant downregulation in neuroprotective intracellular mediators. In this study, we aimed at investigating the neuroprotective effects of p75NTR modulation by the small molecule LM11A-31 in a rotenone-induced neuronal model of PD. Differentiated SH-SY5Y cells were treated with 100 nM rotenone, with or without 500 nM LM11A-31. Our results show that LM11A-31 effectively mitigates PD phenotype by enhancing cell viability, reducing apoptosis, mitigating α-synuclein aggregation, and partially restoring neuromorphological features. Mitochondrial integrity was preserved, likely through the upregulation of transcription factors involved in mitochondrial biogenesis, namely PGC-1α and PPARs. LM11A-31 treatment also reduced oxidative damage to macromolecules, normalizing Nrf2 expression and enhancing protein S-glutathionylation. The antioxidant effect of p75NTR modulation may be partially attributed to the suppression of the NADPH oxidase regulatory subunits p22PHOX and p47PHOX. Additionally, LM11A-31 restored cholesterol homeostasis disrupted by rotenone, as evidenced by the increased NPC1 expression and lysosomal localization, normalized HMGCR levels, and reduced intracellular cholesterol accumulation. Collectively, these findings demonstrate that p75NTR modulation via LM11A-31 exerts neuroprotective effects by targeting key pathological features of PD, including oxidative damage, mitochondrial derangements, and cholesterol dysmetabolism, supporting its potential as a promising therapeutic tool in PD treatment.</p></div>","PeriodicalId":719,"journal":{"name":"Neurochemical Research","volume":"50 5","pages":""},"PeriodicalIF":3.8,"publicationDate":"2025-10-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://link.springer.com/content/pdf/10.1007/s11064-025-04569-7.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145210796","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":"GsMTx4 Mitigates Neuroinflammation and Promotes Functional Recovery by Maintaining Microenvironmental Homeostasis During the Acute Phase After Traumatic Brain Injury in Mice","authors":"Rui Hong,&nbsp;Chen Xu,&nbsp;Xuyang Wang,&nbsp;Lin Zhang,&nbsp;Heli Cao,&nbsp;Yao Jing,&nbsp;Shiwen Chen","doi":"10.1007/s11064-025-04567-9","DOIUrl":"10.1007/s11064-025-04567-9","url":null,"abstract":"<div><p>Traumatic brain injury (TBI) can lead to secondary brain damage, with post-traumatic neuroinflammation being a crucial indicator of the condition’s progression and a predictor of patient prognosis. However, effective, evidence-based pharmacotherapy targeting post-TBI neuroinflammation remains lacking. In our study, we show that the use of the mechanosensitive ion channel inhibitor GsMTx4 effectively alleviated neuronal apoptosis and neuroinflammation, thereby ameliorating abnormal neurological behaviors in mice following TBI. Transcriptomic analysis of the tissue surrounding the injury site indicated downregulation of the extracellular matrix(ECM) degradation and inflammation-related signaling pathways. Complementary metabolomic profiling revealed the metabolic signature and a reduced abundance of metabolites associated with inflammatory responses and ECM degradation after treatment. We speculate that GsMTx4 may modulate various proteases, thereby disrupting the ECM degradation–neuroinflammation feedback loop and ultimately attenuating the progression of neuroinflammation-driven secondary brain damage. Immunostaining and functional assays further confirmed that GsMTx4 treatment preserved ECM-related proteins. These findings suggest that GsMTx4 may offer a promising therapeutic approach for the management of secondary damage following TBI.</p></div>","PeriodicalId":719,"journal":{"name":"Neurochemical Research","volume":"50 5","pages":""},"PeriodicalIF":3.8,"publicationDate":"2025-10-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145210611","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":"Frequency-Dependent Mechanism of 24-Hydroxycholesterol-Mediated Modulation of Neurotransmitter Release at the Mouse Neuromuscular Junction: The Role of Reactive Oxygen Species","authors":"Irina V. Kovyazina,&nbsp;Kamilla A. Mukhutdinova,&nbsp;Alexey M. Petrov","doi":"10.1007/s11064-025-04563-z","DOIUrl":"10.1007/s11064-025-04563-z","url":null,"abstract":"<div><p>Neuron-specific enzyme CYP46A1 converts cholesterol to 24-hydroxycholesterol (24-HC), which crosses the brain blood barrier, entering the systemic circulation. Production of 24-HC depends on synaptic and metabolic activity and changes significantly during aging and neurodegenerative diseases. Previously, it was shown that prolonged application of 24-HC (0.4 µM) suppressed recruitment of synaptic vesicles to exocytosis during 20 Hz nerve stimulation acting <i>via</i> elevation of NO synthesis at the mouse neuromuscular junctions (NMJs). Here, using microelectrode recording of postsynaptic responses and fluorescent trackers for endo-exocytosis, NO and reactive oxygen species (ROS) production, the effect of 24-HC on neuromuscular transmission at 10 Hz and 70 Hz nerve firing was studied. At 10 Hz stimulation, 24-HC decreased neurotransmitter release and synaptic vesicle involvement in exocytosis. This was associated with elevation of NO synthesis without marked changes in ROS generation. However, at 70 Hz activity, 24-HC increased the recruitment of synaptic vesicles in exocytosis in combination with attenuation of NO synthesis and enhancement of ROS production. 24-HC-mediated increase in ROS production was suppressed by NADPH-oxidase inhibitor VAS2870, and antioxidant N-acetylcysteine completely prevented 24-HC-dependent potentiation of neurotransmission and suppression of NO synthesis during 70 Hz activity. Similarly, protein kinase C inhibitor chelerythrine blocked 24-HC-mediated enhancement of exocytosis and attenuation of NO generation at 70 Hz stimulation. Thus, 24-HC suppresses neurotransmission at moderate-frequency activity, probably <i>via</i> elevation of NO synthesis, but it potentiates neurotransmitter release and synaptic vesicle recruitment into exocytosis during high-frequency nerve firing via an NADPH oxidase/ROS/protein kinase C 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":"50 5","pages":""},"PeriodicalIF":3.8,"publicationDate":"2025-09-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145197927","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":"Dynamic and Homeostatic Neuron–Astrocyte Interactions at GABAergic Synapses","authors":"Darren Clarke,&nbsp;Jean-Claude Lacaille,&nbsp;Richard Robitaille","doi":"10.1007/s11064-025-04554-0","DOIUrl":"10.1007/s11064-025-04554-0","url":null,"abstract":"<div><p>Astrocytes support neuron function through a range of regulatory mechanisms, including synaptic modulation. There is a more comprehensive understanding of astrocyte contribution to transmission at excitatory synapses than inhibitory synapses. However, the synaptic activity of inhibitory neurons has extensive consequences on neuron activity, circuitry, brain states and function, which is consolidated by the inherent diversity of GABAergic inhibitory neurons. This review provides an overview of the purposeful function of astrocytes at the synapses of GABAergic inhibitory neurons at structural, ionic, molecular, circuit, and behavioral levels and incorporates diversity into the current understanding of inhibitory tripartite synapses.</p></div>","PeriodicalId":719,"journal":{"name":"Neurochemical Research","volume":"50 5","pages":""},"PeriodicalIF":3.8,"publicationDate":"2025-09-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145184454","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":"Hesperidin Attenuates Chronic Stress-Induced Depression via 5-HT2A-Linked Modulation of Neurochemical, Oxidative, and Inflammatory Pathways: Experimental and In Silico Evidence","authors":"Mimansa Kandhwal,&nbsp;Amarjot Kaur Grewal,&nbsp;Varinder Singh,&nbsp;Ojashvi Sharma,&nbsp;Heena Khan,&nbsp;Manjinder Singh,&nbsp;Amit Kumar,&nbsp;Thakur Gurjeet Singh,&nbsp;Tanveer Singh,&nbsp;Sheikh F. Ahmad,&nbsp;Haneen A. Al-Mazroua,&nbsp;Gamaleldin I. Harisa","doi":"10.1007/s11064-025-04562-0","DOIUrl":"10.1007/s11064-025-04562-0","url":null,"abstract":"<div><p>Depression is associated with monoaminergic dysregulation, oxidative stress, and neuroinflammation, with the 5-hydroxytryptamine 2 A (5-HT2A) receptor playing a key role. The present study investigated the antidepressant-like potential of hesperidin (HSP), a citrus-derived flavonoid, administered chronically (100 or 200 mg/kg, orally once daily for 21 days) in mice exposed to chronic unpredictable mild stress (CUMS). These effects were further explored through 5-HT2A-associated neurochemical and molecular mechanisms, highlighting its role in stress-related neuroprotection. Exposure to CUMS produced depressive-like behavior, accompanied by increased corticosterone, oxidative stress, inflammation, and depletion of 5-HT and dopamine. Treatment with HSP effectively reversed these alterations by restoring sucrose preference, reducing immobility time in the forced swim test, and normalizing locomotor activity in the open field test. At the neurochemical level, HSP treatment reinstated 5-HT and dopamine levels, reduced corticosterone, and attenuated oxidative (MDA, GSH, SOD, catalase) and inflammatory (NF-κB, IL-1β, IL-6, TNF-α) markers. Moreover, HSP improved neuronal architecture, underscoring its neuroprotective potential. Co-administration of the 5-HT2A receptor agonist, (±)-2,5-dimethoxy-4-iodoamphetamine hydrochloride (DOI, 5 mg/kg, subcutaneously, once daily during the 21-day protocol) abolished HSP’s effects, implicating 5-HT2A antagonism in its mechanism. In silico studies confirmed strong and stable binding of HSP to 5-HT2A receptors (− 72.99 kcal/mol), with key interactions involving Trp151, Asp155, Ser159, and Phe340. Molecular dynamics simulations (100 ns) supported complex stability. These results suggest that HSP exerts antidepressant-like effects by modulating 5-HT2A receptors, restoring HPA axis balance, reducing oxidative stress and neuroinflammation, and normalizing monoaminergic function.</p></div>","PeriodicalId":719,"journal":{"name":"Neurochemical Research","volume":"50 5","pages":""},"PeriodicalIF":3.8,"publicationDate":"2025-09-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145184457","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":"A Sleeping Opportunity Does Not Restore Hippocampal Alterations Induced by 10 Days of Sleep Restriction in Rats","authors":"Jesús Enrique García-Aviles,&nbsp;Jessica J. Avilez-Avilez,&nbsp;Josué Sánchez-Hernández,&nbsp;Camila Patlán-Márquez,&nbsp;Javier Rodríguez-Alpízar,&nbsp;Fernanda Michell Becerril-Mercado,&nbsp;Adriana Jiménez,&nbsp;Natalí N. Guerrero-Vargas,&nbsp;Jean-Pascal Morin,&nbsp;Melissa Rodríguez-García,&nbsp;Joaquín Manjarrez-Marmolejo,&nbsp;Beatriz Gómez-González,&nbsp;Rosalinda Guevara-Guzmán,&nbsp;Mara A. Guzmán-Ruiz","doi":"10.1007/s11064-025-04561-1","DOIUrl":"10.1007/s11064-025-04561-1","url":null,"abstract":"<div><p>Sleep loss has been implicated in age-related cognitive decline. Experimental sleep restriction (SR) alters the physiology of multiple brain regions and increases blood–brain barrier (BBB) permeability. Among these regions, the hippocampus of both humans and rodents shows alterations that endure longer than in other areas such as the basal ganglia and hypothalamus. In the present study, adult male rats were subjected to 10 days of SR using the modified multiple platform method (MMPM). Immediately after restriction, SR animals exhibited increased IBA-1 immunoreactivity (IR) and cell number, consistent with microglial activation; these morphological changes persisted after a 4 h recovery period. Synaptophysin (Syn) expression was significantly reduced after SR and remained decreased following rest, while the pERK/ERK ratio was significantly increased by the end of the recovery window. These molecular alterations were accompanied by disrupted hippocampal local field potentials (LFPs), characterized by increased alpha and beta activity and reduced delta and theta power. Importantly, SR rats showed impaired short-term memory in the novel object and object location recognition tests after the recovery period. Together, these findings demonstrate that subchronic SR induces persistent microglial and synaptic alterations and abnormal ERK signaling that remain after short rest, correlating with hippocampal network dysfunction and memory impairment.</p></div>","PeriodicalId":719,"journal":{"name":"Neurochemical Research","volume":"50 5","pages":""},"PeriodicalIF":3.8,"publicationDate":"2025-09-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12479644/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145184500","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":"Ligustilide Ameliorates Traumatic Brain Injury in Aged Mice by Attenuating Microglia-Mediated Neuroinflammation","authors":"Jianfei Wu,&nbsp;Binyou Wang,&nbsp;Youguo Tan,&nbsp;Kezhi Liu,&nbsp;Xin Liu,&nbsp;Shuang Liu,&nbsp;Duanfang Cai,&nbsp;Yu Liu","doi":"10.1007/s11064-025-04560-2","DOIUrl":"10.1007/s11064-025-04560-2","url":null,"abstract":"<div><p>Traumatic brain injury (TBI) is common in the aged population and rapidly triggers a pro-inflammatory response in microglia, leading to severe secondary damage. Ligustilide (LIG), a natural compound with excellent blood-brain barrier (BBB) penetration, shows great potential in neuroprotection, primarily due to its anti-inflammatory, antioxidant, and pro-autophagic properties. However, the role of LIG in elderly TBI remains unclear. This study aims to investigate the effects of LIG on elderly TBI and explore its mechanisms of action. In vivo, we assessed the impact of LIG on behavioral outcomes in elderly TBI mice using the modified Neurological Severity Score (mNSS), open field test (OFT), and Morris water maze (MWM) experiment. We also measured the expression of microglial polarization-related proteins and pro-inflammatory cytokines, as well as the distribution and expression of neuronal marker NeuN and astrocytic marker GFAP. In vitro, we examined the effects of LIG on reactive oxygen species (ROS), mitochondrial membrane potential changes, and apoptosis rates in oxygen-glucose deprivation (OGD) BV-2 cells, as well as the expression of microglial polarization-related proteins. The results demonstrated that LIG promoted the polarization of microglia from the M1 to M2 phenotype in the brain injury side, reduced the release of inflammatory factors, enhanced autophagy, ensured neuronal survival, and improved neurological deficits and memory impairments in aged TBI mice. In conclusion, LIG attenuates TBI pathology in aged mice by driving microglial polarization from M1 to M2 phenotypes and enhancing autophagy. This provides a new therapeutic strategy for TBI in aged males.</p></div>","PeriodicalId":719,"journal":{"name":"Neurochemical Research","volume":"50 5","pages":""},"PeriodicalIF":3.8,"publicationDate":"2025-09-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145145403","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":"The Active Astrocyte: Calcium Dynamics, Circuit Modulation, and Targets for Intervention","authors":"Dmitri A. Rusakov,&nbsp;Thomas P. Jensen,&nbsp;Olga Tyurikova","doi":"10.1007/s11064-025-04553-1","DOIUrl":"10.1007/s11064-025-04553-1","url":null,"abstract":"<div><p>Astrocytes, once considered passive support cells, have emerged as active participants in synaptic communication through Ca²⁺-dependent molecular signalling often referred to as gliotransmission. This review highlights the pioneering contributions of Giorgio Carmignoto, whose work has helped to redefine astrocytes as integral components of the tripartite synapse. Central to this paradigm shift is the role of astrocytic Ca²⁺ signalling in modulating synaptic activity, plasticity, and network behaviour. Carmignoto’s research demonstrated that intracellular Ca²⁺ fluctuations in astrocytes trigger the release of signalling molecules, influencing both excitatory and inhibitory neuronal circuits. These discoveries extended to network-level phenomena, implicating astrocytic Ca²⁺ waves in pathological states like epilepsy. Technologically, Carmignoto advanced astroglial research by employing genetically encoded calcium indicators, optogenetic tools, and cutting-edge imaging methods, including multi-photon microscopy, to observe astrocyte activity in vivo. His work also contributed to automated data analysis pipelines that uncover fine-scale astrocytic microdomain dynamics. In the context of pathology, Carmignoto’s studies related astrocytic dysfunction to epilepsy and dopaminergic dysregulation, suggesting new therapeutic avenues through astrocyte-specific interventions. Despite these advances, challenges remain in defining gliotransmitter mechanisms, understanding astrocyte heterogeneity, and developing tools for precise functional manipulation.</p></div>","PeriodicalId":719,"journal":{"name":"Neurochemical Research","volume":"50 5","pages":""},"PeriodicalIF":3.8,"publicationDate":"2025-09-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://link.springer.com/content/pdf/10.1007/s11064-025-04553-1.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145145400","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}