[{"citation":{"ama":"Martín‐Belmonte A, Aguado C, Alfaro‐Ruiz R, et al. Nanoarchitecture of CaV&#62;2.1 channels and GABAB receptors in the mouse hippocampus: Impact of APP/PS1 pathology. <i>Brain Pathology</i>. 2025;35(2). doi:<a href=\"https://doi.org/10.1111/bpa.13279\">10.1111/bpa.13279</a>","chicago":"Martín‐Belmonte, Alejandro, Carolina Aguado, Rocío Alfaro‐Ruiz, Akos Kulik, Luis de la Ossa, Ana Esther Moreno‐Martínez, Samuel Alberquilla, et al. “Nanoarchitecture of CaV&#62;2.1 Channels and GABAB Receptors in the Mouse Hippocampus: Impact of APP/PS1 Pathology.” <i>Brain Pathology</i>. Wiley, 2025. <a href=\"https://doi.org/10.1111/bpa.13279\">https://doi.org/10.1111/bpa.13279</a>.","short":"A. Martín‐Belmonte, C. Aguado, R. Alfaro‐Ruiz, A. Kulik, L. de la Ossa, A.E. Moreno‐Martínez, S. Alberquilla, L. García‐Carracedo, M. Fernández, A. Fajardo‐Serrano, E. Aso, R. Shigemoto, E.D. Martín, Y. Fukazawa, F. Ciruela, R. Luján, Brain Pathology 35 (2025).","apa":"Martín‐Belmonte, A., Aguado, C., Alfaro‐Ruiz, R., Kulik, A., de la Ossa, L., Moreno‐Martínez, A. E., … Luján, R. (2025). Nanoarchitecture of CaV&#62;2.1 channels and GABAB receptors in the mouse hippocampus: Impact of APP/PS1 pathology. <i>Brain Pathology</i>. Wiley. <a href=\"https://doi.org/10.1111/bpa.13279\">https://doi.org/10.1111/bpa.13279</a>","ieee":"A. Martín‐Belmonte <i>et al.</i>, “Nanoarchitecture of CaV&#62;2.1 channels and GABAB receptors in the mouse hippocampus: Impact of APP/PS1 pathology,” <i>Brain Pathology</i>, vol. 35, no. 2. Wiley, 2025.","mla":"Martín‐Belmonte, Alejandro, et al. “Nanoarchitecture of CaV&#62;2.1 Channels and GABAB Receptors in the Mouse Hippocampus: Impact of APP/PS1 Pathology.” <i>Brain Pathology</i>, vol. 35, no. 2, e13279, Wiley, 2025, doi:<a href=\"https://doi.org/10.1111/bpa.13279\">10.1111/bpa.13279</a>.","ista":"Martín‐Belmonte A, Aguado C, Alfaro‐Ruiz R, Kulik A, de la Ossa L, Moreno‐Martínez AE, Alberquilla S, García‐Carracedo L, Fernández M, Fajardo‐Serrano A, Aso E, Shigemoto R, Martín ED, Fukazawa Y, Ciruela F, Luján R. 2025. Nanoarchitecture of CaV&#62;2.1 channels and GABAB receptors in the mouse hippocampus: Impact of APP/PS1 pathology. Brain Pathology. 35(2), e13279."},"year":"2025","date_published":"2025-03-01T00:00:00Z","publication_status":"published","doi":"10.1111/bpa.13279","publisher":"Wiley","article_processing_charge":"Yes","publication_identifier":{"eissn":["1750-3639"],"issn":["1015-6305"]},"tmp":{"legal_code_url":"https://creativecommons.org/licenses/by-nc-nd/4.0/legalcode","image":"/images/cc_by_nc_nd.png","short":"CC BY-NC-ND (4.0)","name":"Creative Commons Attribution-NonCommercial-NoDerivatives 4.0 International (CC BY-NC-ND 4.0)"},"license":"https://creativecommons.org/licenses/by-nc-nd/4.0/","department":[{"_id":"RySh"}],"month":"03","date_updated":"2025-05-19T13:58:12Z","title":"Nanoarchitecture of CaV>2.1 channels and GABAB receptors in the mouse hippocampus: Impact of APP/PS1 pathology","article_number":"e13279","isi":1,"oa_version":"Published Version","volume":35,"day":"01","quality_controlled":"1","external_id":{"isi":["001250034200001"],"pmid":["38887180"]},"abstract":[{"lang":"eng","text":"Voltage-gated CaV2.1 (P/Q-type) Ca2+ channels play a crucial role in regulating neurotransmitter release, thus contributing to synaptic plasticity and to processes such as learning and memory. Despite their recognized importance in neural function, there is limited information on their potential involvement in neurodegenerative conditions such as Alzheimer's disease (AD). Here, we aimed to explore the impact of AD pathology on the density and nanoscale compartmentalization of CaV2.1 channels in the hippocampus in association with GABAB receptors. Histoblotting experiments showed that the density of CaV2.1 channel was significantly reduced in the hippocampus of APP/PS1 mice in a laminar-dependent manner. CaV2.1 channel was enriched in the active zone of the axon terminals and was present at a very low density over the surface of dendritic tree of the CA1 pyramidal cells, as shown by quantitative SDS-digested freeze-fracture replica labelling (SDS-FRL). In APP/PS1 mice, the density of CaV2.1 channel in the active zone was significantly reduced in the strata radiatum and lacunosum-moleculare, while it remained unaltered in the stratum oriens. The decline in Cav2.1 channel density was found to be associated with a corresponding impairment in the GABAergic synaptic function, as evidenced by electrophysiological experiments carried out in the hippocampus of APP/PS1 mice. Remarkably, double SDS-FRL showed a co-clustering of CaV2.1 channel and GABAB1 receptor in nanodomains (~40–50 nm) in wild type mice, while in APP/PS1 mice this nanoarchitecture was absent. Together, these findings suggest that the AD pathology-induced reduction in CaV2.1 channel density and CaV2.1-GABAB1 de-clustering may play a role in the synaptic transmission alterations shown in the AD hippocampus. Therefore, uncovering these layer-dependent changes in P/Q calcium currents associated with AD pathology can benefit the development of future strategies for AD management."}],"article_type":"original","OA_type":"gold","oa":1,"OA_place":"publisher","_id":"17293","DOAJ_listed":"1","file_date_updated":"2025-04-16T09:56:08Z","issue":"2","type":"journal_article","acknowledgement":"Funding sources were Spanish Ministerio de Economía y Competitividad, Junta de Comunidades de Castilla-La Mancha (Spain), Life Science Innovation Center at University of Fukui and German Research Foundation.\r\nGrants RTI2018-095812-B-I00 and PID2021-125875OB-I00 funded by MCIN/AEI/10.13039/501100011033 and by “ERDF A way of making Europe” to Rafael Luján. This study was also supported by a grant from Junta de Comunidades de Castilla-La Mancha (SBPLY/17/180501/000229 and SBPLY/21/180501/000064) and Universidad de Castilla-La Mancha (2023-GRIN-34187) to Rafael Luján, and Life Science Innovation Center (Research and Education Program for Life Science) at University of Fukui and JSPS KAKENHI Grant Numbers 16H04662, 17K19446, 18H05120 to Yugo Fukazawa and Margarita Salas fellowship from Ministerio de Universidades and Universidad de Castilla-La Mancha to Alejandro Martín-Belmonte. German Research Foundation (DFG FOR 2143) and BIOSS-2 to Akos Kulik.","user_id":"2DF688A6-F248-11E8-B48F-1D18A9856A87","author":[{"first_name":"Alejandro","full_name":"Martín‐Belmonte, Alejandro","last_name":"Martín‐Belmonte"},{"first_name":"Carolina","full_name":"Aguado, Carolina","last_name":"Aguado"},{"first_name":"Rocío","full_name":"Alfaro‐Ruiz, Rocío","last_name":"Alfaro‐Ruiz"},{"last_name":"Kulik","full_name":"Kulik, Akos","first_name":"Akos"},{"first_name":"Luis","full_name":"de la Ossa, Luis","last_name":"de la Ossa"},{"first_name":"Ana Esther","last_name":"Moreno‐Martínez","full_name":"Moreno‐Martínez, Ana Esther"},{"last_name":"Alberquilla","full_name":"Alberquilla, Samuel","first_name":"Samuel"},{"first_name":"Lucía","last_name":"García‐Carracedo","full_name":"García‐Carracedo, Lucía"},{"first_name":"Miriam","last_name":"Fernández","full_name":"Fernández, Miriam"},{"last_name":"Fajardo‐Serrano","full_name":"Fajardo‐Serrano, Ana","first_name":"Ana"},{"first_name":"Ester","full_name":"Aso, Ester","last_name":"Aso"},{"first_name":"Ryuichi","orcid":"0000-0001-8761-9444","id":"499F3ABC-F248-11E8-B48F-1D18A9856A87","full_name":"Shigemoto, Ryuichi","last_name":"Shigemoto"},{"full_name":"Martín, Eduardo D.","last_name":"Martín","first_name":"Eduardo D."},{"full_name":"Fukazawa, Yugo","last_name":"Fukazawa","first_name":"Yugo"},{"first_name":"Francisco","last_name":"Ciruela","full_name":"Ciruela, Francisco"},{"last_name":"Luján","full_name":"Luján, Rafael","first_name":"Rafael"}],"status":"public","date_created":"2024-07-22T07:48:20Z","scopus_import":"1","has_accepted_license":"1","language":[{"iso":"eng"}],"publication":"Brain Pathology","file":[{"content_type":"application/pdf","date_updated":"2025-04-16T09:56:08Z","file_name":"2025_BrainPathology_MartinBelmonte.pdf","file_id":"19582","creator":"dernst","checksum":"75a172800ab2e949abb66fba97cf70f0","date_created":"2025-04-16T09:56:08Z","file_size":8767863,"relation":"main_file","success":1,"access_level":"open_access"}],"ddc":["570"],"intvolume":"        35","pmid":1},{"user_id":"2DF688A6-F248-11E8-B48F-1D18A9856A87","author":[{"full_name":"Martín-Belmonte, Alejandro","last_name":"Martín-Belmonte","first_name":"Alejandro"},{"first_name":"Carolina","full_name":"Aguado, Carolina","last_name":"Aguado"},{"full_name":"Alfaro-Ruíz, Rocío","last_name":"Alfaro-Ruíz","first_name":"Rocío"},{"full_name":"Moreno-Martínez, Ana Esther","last_name":"Moreno-Martínez","first_name":"Ana Esther"},{"first_name":"Luis","last_name":"De La Ossa","full_name":"De La Ossa, Luis"},{"first_name":"José","full_name":"Martínez-Hernández, José","last_name":"Martínez-Hernández"},{"first_name":"Alain","last_name":"Buisson","full_name":"Buisson, Alain"},{"first_name":"Simon","last_name":"Früh","full_name":"Früh, Simon"},{"first_name":"Bernhard","last_name":"Bettler","full_name":"Bettler, Bernhard"},{"first_name":"Ryuichi","orcid":"0000-0001-8761-9444","full_name":"Shigemoto, Ryuichi","id":"499F3ABC-F248-11E8-B48F-1D18A9856A87","last_name":"Shigemoto"},{"last_name":"Fukazawa","full_name":"Fukazawa, Yugo","first_name":"Yugo"},{"first_name":"Rafael","last_name":"Luján","full_name":"Luján, Rafael"}],"type":"journal_article","file_date_updated":"2020-09-22T09:47:19Z","issue":"3","_id":"7207","oa":1,"page":"554-575","intvolume":"        30","pmid":1,"file":[{"creator":"dernst","file_id":"8554","file_name":"2020_BrainPathology_MartinBelmonte.pdf","date_updated":"2020-09-22T09:47:19Z","content_type":"application/pdf","access_level":"open_access","success":1,"relation":"main_file","file_size":4220935,"date_created":"2020-09-22T09:47:19Z","checksum":"549cc1b18f638a21d17a939ba5563fa9"}],"ddc":["570"],"has_accepted_license":"1","publication":"Brain Pathology","language":[{"iso":"eng"}],"status":"public","date_created":"2019-12-22T23:00:43Z","scopus_import":"1","title":"Reduction in the neuronal surface of post and presynaptic GABA>B< receptors in the hippocampus in a mouse model of Alzheimer's disease","isi":1,"license":"https://creativecommons.org/licenses/by/4.0/","tmp":{"legal_code_url":"https://creativecommons.org/licenses/by/4.0/legalcode","image":"/images/cc_by.png","name":"Creative Commons Attribution 4.0 International Public License (CC-BY 4.0)","short":"CC BY (4.0)"},"date_updated":"2025-07-10T11:54:22Z","department":[{"_id":"RySh"}],"month":"05","publication_status":"published","article_processing_charge":"No","publisher":"Wiley","publication_identifier":{"issn":["1015-6305"],"eissn":["1750-3639"]},"doi":"10.1111/bpa.12802","year":"2020","date_published":"2020-05-01T00:00:00Z","citation":{"chicago":"Martín-Belmonte, Alejandro, Carolina Aguado, Rocío Alfaro-Ruíz, Ana Esther Moreno-Martínez, Luis De La Ossa, José Martínez-Hernández, Alain Buisson, et al. “Reduction in the Neuronal Surface of Post and Presynaptic GABA&#62;B&#60; Receptors in the Hippocampus in a Mouse Model of Alzheimer’s Disease.” <i>Brain Pathology</i>. Wiley, 2020. <a href=\"https://doi.org/10.1111/bpa.12802\">https://doi.org/10.1111/bpa.12802</a>.","ama":"Martín-Belmonte A, Aguado C, Alfaro-Ruíz R, et al. Reduction in the neuronal surface of post and presynaptic GABA&#62;B&#60; receptors in the hippocampus in a mouse model of Alzheimer’s disease. <i>Brain Pathology</i>. 2020;30(3):554-575. doi:<a href=\"https://doi.org/10.1111/bpa.12802\">10.1111/bpa.12802</a>","apa":"Martín-Belmonte, A., Aguado, C., Alfaro-Ruíz, R., Moreno-Martínez, A. E., De La Ossa, L., Martínez-Hernández, J., … Luján, R. (2020). Reduction in the neuronal surface of post and presynaptic GABA&#62;B&#60; receptors in the hippocampus in a mouse model of Alzheimer’s disease. <i>Brain Pathology</i>. Wiley. <a href=\"https://doi.org/10.1111/bpa.12802\">https://doi.org/10.1111/bpa.12802</a>","short":"A. Martín-Belmonte, C. Aguado, R. Alfaro-Ruíz, A.E. Moreno-Martínez, L. De La Ossa, J. Martínez-Hernández, A. Buisson, S. Früh, B. Bettler, R. Shigemoto, Y. Fukazawa, R. Luján, Brain Pathology 30 (2020) 554–575.","mla":"Martín-Belmonte, Alejandro, et al. “Reduction in the Neuronal Surface of Post and Presynaptic GABA&#62;B&#60; Receptors in the Hippocampus in a Mouse Model of Alzheimer’s Disease.” <i>Brain Pathology</i>, vol. 30, no. 3, Wiley, 2020, pp. 554–75, doi:<a href=\"https://doi.org/10.1111/bpa.12802\">10.1111/bpa.12802</a>.","ieee":"A. Martín-Belmonte <i>et al.</i>, “Reduction in the neuronal surface of post and presynaptic GABA&#62;B&#60; receptors in the hippocampus in a mouse model of Alzheimer’s disease,” <i>Brain Pathology</i>, vol. 30, no. 3. Wiley, pp. 554–575, 2020.","ista":"Martín-Belmonte A, Aguado C, Alfaro-Ruíz R, Moreno-Martínez AE, De La Ossa L, Martínez-Hernández J, Buisson A, Früh S, Bettler B, Shigemoto R, Fukazawa Y, Luján R. 2020. Reduction in the neuronal surface of post and presynaptic GABA&#62;B&#60; receptors in the hippocampus in a mouse model of Alzheimer’s disease. Brain Pathology. 30(3), 554–575."},"abstract":[{"text":"The hippocampus plays key roles in learning and memory and is a main target of Alzheimer's disease (AD), which causes progressive memory impairments. Despite numerous investigations about the processes required for the normal hippocampal functions, the neurotransmitter receptors involved in the synaptic deficits by which AD disables the hippocampus are not yet characterized. By combining histoblots, western blots, immunohistochemistry and high‐resolution immunoelectron microscopic methods for GABAB receptors, this study provides a quantitative description of the expression and the subcellular localization of GABAB1 in the hippocampus in a mouse model of AD at 1, 6 and 12 months of age. Western blots and histoblots showed that the total amount of protein and the laminar expression pattern of GABAB1 were similar in APP/PS1 mice and in age‐matched wild‐type mice. In contrast, immunoelectron microscopic techniques showed that the subcellular localization of GABAB1 subunit did not change significantly in APP/PS1 mice at 1 month of age, was significantly reduced in the stratum lacunosum‐moleculare of CA1 pyramidal cells at 6 months of age and significantly reduced at the membrane surface of CA1 pyramidal cells at 12 months of age. This reduction of plasma membrane GABAB1 was paralleled by a significant increase of the subunit at the intracellular sites. We further observed a decrease of membrane‐targeted GABAB receptors in axon terminals contacting CA1 pyramidal cells. Our data demonstrate compartment‐ and age‐dependent reduction of plasma membrane‐targeted GABAB receptors in the CA1 region of the hippocampus, suggesting that this decrease might be enough to alter the GABAB‐mediated synaptic transmission taking place in AD.","lang":"eng"}],"article_type":"original","external_id":{"isi":["000502270900001"],"pmid":["31729777"]},"quality_controlled":"1","project":[{"grant_number":"720270","_id":"25CBA828-B435-11E9-9278-68D0E5697425","name":"Human Brain Project Specific Grant Agreement 1","call_identifier":"H2020"},{"grant_number":"785907","name":"Human Brain Project Specific Grant Agreement 2","_id":"26436750-B435-11E9-9278-68D0E5697425","call_identifier":"H2020"}],"day":"01","volume":30,"oa_version":"Published Version","ec_funded":1}]