Journal of Neurochemistry最新文献

{"title":"Splice Type-Specific Effects of Gαo Subunits on Cerebellar Anatomy and Synapse Formation","authors":"Markus Höltje,&nbsp;Anton Wolkowicz,&nbsp;Gudrun Ahnert-Hilger","doi":"10.1111/jnc.70512","DOIUrl":"10.1111/jnc.70512","url":null,"abstract":"<p>This study investigated the effect of single Gα_o1 and Gα_o2, as well as double Gα_o1/2 knockout on the cerebellar anatomy and synapse formation. The alpha subunit of the G protein Go exists in two splice variants. Knockout of certain Gαo subtypes result in strong—mainly motor—deficits in mice, and mutations in the responsible gene locus in humans can result in severe encephalopathies. We aimed to decipher the hitherto incompletely understood contribution of the individual Gα_o subunits to the anatomy and synapse formation of the cerebellum. Knockout of Gα_o1 reduced the size of the cerebellum by 11%, accompanied by maximal reductions of the molecular layer thickness in the central lobule III (−30%) and molecular layer area in the uvula (−33%). Knockout of Gα_o2 increased cerebellar size, molecular layer thickness in central lobule II (+18.6%), and area of the culmen (+37%). Combined deletion of Gα_o1 and Gα_o2 reduced cerebellar size by 12%, molecular layer thickness and area of the declive (by −27.3% and −23.4%, respectively). Moreover, VGLUT2-positive climbing fiber contacts to Purkinje cells were reduced in Gα_o1 knockout mice (on average by 40%). Similarly, VGLUT1 expression was reduced (on average by 17.3%). The knockout of Gα_o2 promoted climbing fiber contacts (+14.3% on average, at a maximum of +52.6% in the central lobule II), VGLUT1 was less affected. Double knockout mice exhibited negative effects on VGLUT2 (−35% overall number) and VGLUT1 (−23% on average in expression levels). VGAT-positive synaptic contacts were also diminished for Gα_o1 and double knockout (−25% and −31% overall number, respectively) and increased for Gα_o2 knockout (+13% on average). In line with this, negative effects on the dendritic outgrowth of Purkinje cells were observed in both Gα_o1^−/− and Gα_o^−/−mice, while knockout of Gα_o2 promoted dendrite outgrowth. Taken together, the two Gαo splice variants contrarily contribute to the development of the cerebellum, with Gα_o1 representing the dominant subunit.</p><p>\u0000 \u0000 <figure>\u0000 <div><picture>\u0000 <source></source></picture><p></p>\u0000 </div>\u0000 </figure>\u0000 </p>","PeriodicalId":16527,"journal":{"name":"Journal of Neurochemistry","volume":"170 7","pages":""},"PeriodicalIF":4.6,"publicationDate":"2026-07-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1111/jnc.70512","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148368690","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":"GM1-Oligosaccharide Rescues Rotenone-Impaired Neuronal Polarization Through RhoA/ROCK Modulation and Mitochondrial Protection","authors":"Pablo E. A. Rodríguez,&nbsp;Guillermo N. Colmano,&nbsp;Andrea Pellegrini,&nbsp;María E. Mariani,&nbsp;Silvana B. Rosso,&nbsp;Gonzalo Quassollo,&nbsp;Pablo Helguera,&nbsp;Mariano Bisbal,&nbsp;Gerardo D. Fidelio,&nbsp;Mónica S. Sanchez","doi":"10.1111/jnc.70505","DOIUrl":"https://doi.org/10.1111/jnc.70505","url":null,"abstract":"<div>\u0000 \u0000 <p>Neuronal polarization is a fundamental process in the formation of functional neural circuits, relying on the precise coordination between cytoskeletal regulatory signals and mechanisms that sustain cellular integrity. Disruption of these processes compromises neuronal differentiation and survival, and various neurotoxic compounds, including certain pesticides, have been associated with such dysfunctions. In this context, identifying molecules that counteract these detrimental effects is of significant therapeutic interest. Neuronal polarization is essential for the establishment of functional neural circuits and relies on coordinated regulation of actin cytoskeleton dynamics, RhoA/ROCK signaling, and mitochondrial function. Here, we investigated the neuroprotective and neurorestorative potential of the ganglioside GM1 and its oligosaccharide derivative, osGM1, in primary hippocampal pyramidal neurons derived from embryonic day 18 (E18) rat embryos exposed to the mitochondrial neurotoxin rotenone. Rotenone induced a marked arrest of neuronal development, impaired axonal elongation, and disrupted mitochondrial organization and functional status. Both GM1 and osGM1 promoted recovery of neuronal polarity and axonal growth, exerting protective and restorative effects even under continuous toxin exposure, with osGM1 showing superior efficacy. Notably, osGM1 also reversed axonal growth deficits caused by pathological actin stabilization. Mechanistically, osGM1 normalized rotenone-induced hyperactivation of the RhoA/ROCK pathway without altering basal signaling and partially restored mitochondrial network integrity and functional activity. Collectively, these findings identify osGM1 as a multi-target modulator of cytoskeletal and mitochondrial dysfunction and support its translational potential as a therapeutic strategy to counteract neurotoxin-induced neuronal damage.</p>\u0000 <p>\u0000 \u0000 <figure>\u0000 <div><picture>\u0000 <source></source></picture><p></p>\u0000 </div>\u0000 </figure>\u0000 </p>\u0000 </div>","PeriodicalId":16527,"journal":{"name":"Journal of Neurochemistry","volume":"170 7","pages":""},"PeriodicalIF":4.6,"publicationDate":"2026-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148358086","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":"Understanding Human Cortical Expansion Using Pluripotent Stem Cell-Derived Brain Organoids: Insights Into Progenitor Evolution and Diversity.","authors":"Wendy W Y Choi, Julien Muffat, Yun Li","doi":"10.1111/jnc.70527","DOIUrl":"10.1111/jnc.70527","url":null,"abstract":"<p><p>The evolution of the human brain underlies our higher-order cognitive functions. In particular, the cerebral cortex, the outermost layer of the brain, has rapidly evolved to contain a disproportionately large number of neurons relative to the rest of the brain. Much of this expansion is attributed to the enlargement and diversification of the pool of neural precursors, which proliferate and differentiate into the neurons and glia of the brain. How the human cerebral cortex has evolved remains an active area of investigation. With the advent of pluripotent stem cell and brain organoid technologies, comparative genomic studies between humans, mice, and nonhuman primates have identified human-specific genes or pathways during neurodevelopment. The utility of these models relies on the ability of brain organoids to preserve the cytoarchitecture and species-specific developmental trajectories of diverse neural and glial cell types that are observed in vivo. This review will discuss how brain organoids recapitulate aspects of interspecies differences during cortical development, specifically neural precursor expansion, neurogenesis, and gliogenesis, and how these models can be improved to enable a deeper understanding of human brain evolution. Unraveling the cellular and molecular mechanisms underlying cross-species differences in brain expansion could also provide key insights into neurodevelopmental diseases, particularly those where brain size is affected.</p>","PeriodicalId":16527,"journal":{"name":"Journal of Neurochemistry","volume":"170 7","pages":"e70527"},"PeriodicalIF":4.6,"publicationDate":"2026-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13386524/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148536077","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":"LRRK2 Mutation Alters Dopamine D2 Receptor Localization in Induced Pluripotent Stem Cells-Derived Astrocytes From Parkinson's Disease Patients: Implications for Neuronal Damage","authors":"Veronica Mutti,&nbsp;Federica Bono,&nbsp;Zaira Tomasoni,&nbsp;Dounia Fadel,&nbsp;Chiara Gnutti,&nbsp;Giulia Sbrini,&nbsp;Carolina Gaudenzi,&nbsp;Valentina Salvi,&nbsp;Daniela Bosisio,&nbsp;Isabella Russo,&nbsp;Silvia Bolognin,&nbsp;Jens C. Schwamborn,&nbsp;Cristina Missale,&nbsp;Chiara Fiorentini","doi":"10.1111/jnc.70510","DOIUrl":"https://doi.org/10.1111/jnc.70510","url":null,"abstract":"<p>Astrocytes, the most abundant glia subtype, exert a wide range of functions, many of which are essential for maintaining neuronal homeostasis. A variety of neurotransmitter receptors are expressed on astrocytes allowing them to sense extracellular signals and respond by releasing neuroactive mediators. Among them, a wide variety of G protein-coupled receptors have been detected, including those for dopamine (DA), known to play a major role in modulating astrocytic activity. Evidence that astrocytic DA D2 receptors (D2R) increase the release of trophic factors and suppress neuroinflammation has been provided. Thus, DA signaling in astrocytes may be crucially involved in the mechanisms underlying the degeneration of DA neurons in Parkinson's disease (PD). In this study, human astrocytes were generated from induced pluripotent stem cell (iPSC) lines derived from two PD patients bearing G2019S LRRK2 kinase activating mutation. The effect of the PD-related mutation in astrocytes was analyzed, focusing on DA receptor's expression and localization. As expected, astrocytes carrying G2019S mutation in LRRK2 displayed a reactive phenotype with increased secretion of inflammatory cytokines and reduced ability to support DA neurons' trophism in astrocytes/neurons co-culture experiments. Intriguingly, PD astrocytes exhibited reduced membrane expression of D2R. Inhibiting the abnormally increased kinase activity was able to revert the PD astrocytes' reactive phenotype and to rescue the D2R membrane localization. We thus provide new insights into how G2019S mutation in LRRK2, by disrupting the astrocytic physiological localization of D2R, may impair protective DA signaling, resulting in increased neuroinflammation and neuronal damage.</p><p>\u0000 \u0000 <figure>\u0000 <div><picture>\u0000 <source></source></picture><p></p>\u0000 </div>\u0000 </figure>\u0000 </p>","PeriodicalId":16527,"journal":{"name":"Journal of Neurochemistry","volume":"170 7","pages":""},"PeriodicalIF":4.6,"publicationDate":"2026-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1111/jnc.70510","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148358087","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":"Effect of Prenatal and Postnatal Stress in Rats on the Gut Microbiome in Adolescence.","authors":"Rebecca Woods, Elliot F Jennings, Laura Smith, Khairiah Almushri, Liam Hanson, Oriana Gamrot, Ayomide Adetunji, Chiamaka Vera Oguanya, Hamilton Imongan, Kubili John, Emmanuella Omuluche, Michael Harte, Chris Murgatroyd","doi":"10.1111/jnc.70530","DOIUrl":"10.1111/jnc.70530","url":null,"abstract":"<p><p>Previous research suggests that early-life stress (ELS) increases the risk of mental health disorders later in life. It is hypothesised that ELS disrupts the developing gut microbiome, which in turn may alter neuroendocrine and immune system development, thereby increasing disease susceptibility. However, the specific microbial taxa and pathways mediating these effects remain poorly characterised. Here, we used rat models to investigate whether ELS leads to long-term alterations in the gut microbiome. Microbial composition was assessed using 16S rRNA Nanopore sequencing of DNA extracted from faecal pellets of adolescent male and female rats exposed to: (i) early postnatal dexamethasone (DEXA; a synthetic glucocorticoid) or saline control, (ii) prenatal stress (PRS) and controls, or (iii) postnatal stress (POS) and controls. Microbiome structure was evaluated using richness, evenness, dominance and diversity indices. We show that ELS induces model-specific and sex-dependent changes in gut microbiome composition, primarily at the level of overall community structure rather than individual taxa. DEXA exposure produced the most consistent compositional signature, particularly in males, whereas PRS showed minimal detectable effects and POS exhibited a more heterogeneous response characterised by increased dispersion and limited taxonomic shifts. More broadly, these findings demonstrate that integrating beta-diversity analyses with machine learning approaches can identify reproducible microbiome patterns associated with ELS, even in the absence of large taxonomic changes. Applying similar frameworks in larger and longitudinal cohorts will be important to determine how these subtle microbial signatures contribute to long-term physiological outcomes.</p>","PeriodicalId":16527,"journal":{"name":"Journal of Neurochemistry","volume":"170 7","pages":"e70530"},"PeriodicalIF":4.6,"publicationDate":"2026-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13408194/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148603826","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":"Early Hypo-Osmolar Stress Regulates Astrocyte Reactivity After Brain Injury: \"New Insights Into Glial Response to Edema\".","authors":"Camila Vidos, Matías Monteverde Busso, Azul Millán, Carolina Denise Silveri, Emilia Frischknecht, Guadalupe Campaniello, Alberto Javier Ramos, Alejandro Villarreal","doi":"10.1111/jnc.70524","DOIUrl":"10.1111/jnc.70524","url":null,"abstract":"<p><p>Astrocytes are among the first cellular responders to central nervous system injury, yet the mechanisms governing their earliest responses remain incompletely understood. Here, we investigated astrocyte dynamics during the first hours after focal cortical injury induced by cortical devascularization in rats. We observed a rapid and spatially restricted increase in glial fibrillary acidic protein (GFAP) and aquaporin-4 (AQP4) immunoreactivity surrounding the ischemic core as early as 1.5-3.5 h post-lesion, in association with blood-brain barrier disruption and edema-related changes. Within the injury core, astrocytes displayed differential GFAP detection by monoclonal and polyclonal antibodies, together with the appearance of lower-molecular-weight GFAP fragments both in vivo and after oxygen-glucose deprivation in vitro, suggesting GFAP cleavage in severely damaged astrocytes. At the chromatin level, astrocytes proximal to the lesion exhibited reduced histone H3 acetylation, particularly histone 3 acetylation at lysine 9 (H3K9ac), a phenomenon recapitulated in cultured astrocytes exposed to hypo-osmolar stress. This reduction was transient, reversible upon recovery, and prevented by histone deacetylase (HDAC) inhibition. Functionally, hypo-osmolar stress conditioned astrocyte responses to subsequent stimuli, attenuating nuclear factor kappa B (NF-κB) activation and complement 3 (C3) induction after lipopolysaccharide exposure while enhancing proliferative capacity during recovery. Together, these findings identify edema-associated osmotic stress as an early regulator of astrocyte epigenetic state and functional plasticity, suggesting that astrocytes exposed to edema are primed to adopt distinct responses that may contribute to tissue repair and scar formation following brain injury.</p>","PeriodicalId":16527,"journal":{"name":"Journal of Neurochemistry","volume":"170 7","pages":"e70524"},"PeriodicalIF":4.6,"publicationDate":"2026-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13386523/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148536072","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":"High-Resolution Elemental Analysis of Neuromelanin-Containing Organelles in Human Locus Coeruleus.","authors":"Zahraa Berro, Fabio A Zucca, Maria Angels Subirana, Adrian-Marie Philippe, Dirk Schaumlöffel, Anaïs Carpentier, Andrea Capucciati, David Bouvier, Michel Mittelbronn, Jean-Nicolas Audinot, Luigi Zecca, Antje Biesemeier","doi":"10.1111/jnc.70531","DOIUrl":"10.1111/jnc.70531","url":null,"abstract":"<p><p>Neuromelanin-(NM) containing organelles are sub-cellular auto-lysosomal structures composed of three main compartments: NM pigment, protein matrix, and lipid bodies. These organelles accumulate during aging and are found predominantly in the catecholaminergic neurons of Substantia Nigra (SN) and Locus Coeruleus (LC), the main regions affected in Parkinson's disease (PD). NM serves a protective function by sequestering potentially toxic metals like Cu, Fe, and Al. However, NM released from degenerating neurons may lead to a cascade of events resulting in neuroinflammation and neurodegeneration. Therefore, elemental analysis of NM-containing organelles presents a crucial step to understand aging and PD. In LC, such studies are limited because NM isolation requires large postmortem cohorts and analyses may be impaired by tissue processing. By integrating high resolution electron microscopy (EM), nano-secondary ion mass spectrometry (nano-SIMS), and energy dispersive X-ray (EDX) microscpectroscopy, the elemental composition of intact NM-containing organelles was analyzed in seven postmortem LC tissues. Chemical mapping with down to 5-10 nm lateral resolution (EDX) fostered discrimination of structural composition (N, P, S, Cl) and metal storage (Al, Ca, Fe) across neurons and within individual NM-containing organelle sub-compartments (with diameters down to 0.2 μm for lipid bodies) from the same sample. NM-containing organelles were identified by an elemental fingerprint pattern. Metals accumulations were localized predominantly to the NM pigment compartment identified by its pheomelanin-rich portion (S). This confirms NM's role in accumulating physiological as well as potentially toxic metal species. Moreover, semi-quantitative analyses provided insights into inter- and intra-subject NM metal accumulation, showing that S and Fe exhibited a positive aging trend. Hemispheric asymmetry was observed for Al, Ca, and Fe, with higher levels observed in NMs of the right brain hemisphere suggesting region-specific accumulation that warrants further investigation to better understand aging-related changes and the neuronal vulnerability of the LC in PD.</p>","PeriodicalId":16527,"journal":{"name":"Journal of Neurochemistry","volume":"170 7","pages":"e70531"},"PeriodicalIF":4.6,"publicationDate":"2026-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13408184/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148603880","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":"Neural Organoid Models as a Platform for Studying Disease Mechanisms in Amyotrophic Lateral Sclerosis","authors":"Kristel N. Eigenhuis,&nbsp;Roberto Montoro Ferrer,&nbsp;R. Jeroen Pasterkamp","doi":"10.1111/jnc.70513","DOIUrl":"https://doi.org/10.1111/jnc.70513","url":null,"abstract":"<p>Amyotrophic lateral sclerosis (ALS) is a fatal neurodegenerative disorder affecting upper and lower motor neurons leading to muscle wasting. However, structural and molecular abnormalities, including cortical thinning and TDP-43 pathology, extend into frontal, parietal, and temporal areas, pointing to defects across broader cortical regions. The advent of human induced pluripotent stem cell (hiPSC) technology has enabled the generation of human-specific brain cell types in vitro. Here, we provide an overview of the three-dimensional (3D) hiPSC-derived neural organoid platforms used to model cortical structures and to study cortical ALS-associated phenotypes. We review which pathological hallmarks have been recapitulated in these organoids and discuss disease phenotypes reported to date. Further, we comprehensively cover different neural organoid models and experimental strategies, including patient-derived hiPSC models and exogenous pathology induction, while addressing current technical challenges. Together, these advances position neural organoids as an emerging tool to study cell-type-specific and circuit-level mechanisms related to cortical changes in ALS.</p><p>\u0000 \u0000 <figure>\u0000 <div><picture>\u0000 <source></source></picture><p></p>\u0000 </div>\u0000 </figure>\u0000 </p>","PeriodicalId":16527,"journal":{"name":"Journal of Neurochemistry","volume":"170 7","pages":""},"PeriodicalIF":4.6,"publicationDate":"2026-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1111/jnc.70513","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148358019","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":"Parkinson's Disease Cell Transplantation Therapy: A New Dawn With Pluripotent Stem Cell–Based Therapy","authors":"Etsuro Nakanishi,&nbsp;Hodaka Yamakado,&nbsp;Nobukatsu Sawamoto,&nbsp;Jun Takahashi,&nbsp;Ryosuke Takahashi","doi":"10.1111/jnc.70500","DOIUrl":"https://doi.org/10.1111/jnc.70500","url":null,"abstract":"<p>Parkinson's disease (PD), a prevalent neurodegenerative disorder, is characterized by progressive loss of dopaminergic neurons in the midbrain. While dopamine replacement therapy effectively manages early symptoms, its long-term use leads to motor complications, highlighting the urgent need for treatments that directly address the underlying pathological changes. Cell transplantation, which aims to replace the lost dopaminergic neurons, has emerged as a promising approach. Early attempts using fetal ventral mesencephalic (fVM) tissue showed proof-of-concept, with some patients experiencing long-term motor improvement. However, these trials have been hampered by inconsistent results, graft-induced dyskinesia (GID), and significant ethical and logistical issues related to tissue supply. These challenges have shifted the focus to pluripotent stem cells (PSCs), including human-induced pluripotent stem cells (iPSCs) and embryonic stem cells (ESCs), which offer a stable, ethically sound, and scalable source of high-quality cells. Recent clinical trials using PSCs suggest a turning point. All reported clinical trials demonstrated the safety and feasibility of this approach. The need for long-term safety and efficacy data, patient stratification, and techniques to improve graft survival are key areas of future research. Nevertheless, recent clinical trial successes suggest that cell transplantation is moving beyond symptomatic relief to become a truly restorative therapy for PD.</p><p>\u0000 \u0000 <figure>\u0000 <div><picture>\u0000 <source></source></picture><p></p>\u0000 </div>\u0000 </figure>\u0000 </p>","PeriodicalId":16527,"journal":{"name":"Journal of Neurochemistry","volume":"170 7","pages":""},"PeriodicalIF":4.6,"publicationDate":"2026-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1111/jnc.70500","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148358018","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":"Developmentally Regulated Expression and Activity of Sulphotransferases in the Rat Choroid Plexuses.","authors":"Fiona Qiu, Nathalie Strazielle, Anne Denuziere, Jean-François Ghersi-Egea","doi":"10.1111/jnc.70533","DOIUrl":"10.1111/jnc.70533","url":null,"abstract":"<p><p>During development, entry of any substances from the circulation into the brain is tightly regulated by a series of blood-brain interfaces. Notably, the choroid plexuses, which form the blood-cerebrospinal fluid barrier, serve as a key interface for molecular exchange in early life. Control mechanisms within the choroid plexuses include efflux transporters and conjugating enzymes, such as glutathione S-transferases and UDP-glucuronosyltransferases, which have been shown to play key roles in safeguarding the developing brain. Sulphotransferases are another family of conjugating enzymes reported to be highly expressed in the choroid plexus in humans and rats during development. However, their activity and functional significance in the central nervous system remain poorly understood. In the present study, sulphotransferase activity was measured in the lateral and fourth ventricle choroid plexus from rats at embryonic Day 19 and postnatal Day (P)1, 3, 8 and 30. Activity was correlated with expression of isoenzymes by RT-qPCR. Inhibition studies were performed by co-incubating a prototypical sulphotransferase substrate with a potential substrate or inhibitor. Finally, assays in freshly isolated live tissue were conducted to assess sulphoconjugation under more physiologically relevant conditions. Results showed that both sulphotransferase activity and expression of Sult1a1 in the choroid plexus were markedly increased at P1 to P3. This distinct temporal pattern suggests age- and tissue-specific roles of choroidal sulphotransferase activity during the early postnatal period. Interactions with xenobiotics and neuroendocrine factors further suggest that these enzymes may contribute to multiple processes during this critical window, including protection against potentially harmful substances and regulation of neurotransmitters. Furthermore, the observed modulation of choroidal sulphotransferase activity by various exogenous substances suggests that developmental exposure could disrupt sulphotransferase-mediated biological processes, with potential consequences for normal neurodevelopment.</p>","PeriodicalId":16527,"journal":{"name":"Journal of Neurochemistry","volume":"170 7","pages":"e70533"},"PeriodicalIF":4.6,"publicationDate":"2026-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13408200/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148604290","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}