{"entity": "journal", "iuid": "e49710f8062b481c8d4f83c725f0769a", "timestamp": "2026-08-14T12:34:27.510Z", "links": {"self": {"href": "https://publications.scilifelab.se/journal/Brain.json"}, "display": {"href": "https://publications.scilifelab.se/journal/Brain"}}, "title": "Brain", "issn": "1460-2156", "issn-l": "0006-8950", "publications_count": 6, "publications": [{"entity": "publication", "iuid": "e7038b6561ed4a8282747388827a8dac", "links": {"self": {"href": "https://publications.scilifelab.se/publication/e7038b6561ed4a8282747388827a8dac.json"}, "display": {"href": "https://publications.scilifelab.se/publication/e7038b6561ed4a8282747388827a8dac"}}, "title": "Neuroinflammation and neurodegeneration trigger a specific splice form of ribosomal protein S24", "authors": [{"family": "Magadi", "given": "Srivathsa S", "initials": "SS"}, {"family": "Jonson", "given": "Maria", "initials": "M"}, {"family": "Lucena", "given": "Pablo B", "initials": "PB"}, {"family": "Caliandro", "given": "Michele F", "initials": "MF"}, {"family": "Almeida", "given": "Beatriz", "initials": "B"}, {"family": "Bilalli", "given": "Lorina", "initials": "L"}, {"family": "Budinger", "given": "Dimitri", "initials": "D", "orcid": "0000-0001-7002-1091", "researcher": {"href": "https://publications.scilifelab.se/researcher/ecc1d3189e714b89a58b392e2a05eb8e.json"}}, {"family": "Tsoi", "given": "Anna", "initials": "A"}, {"family": "Ntzouni", "given": "Maria", "initials": "M"}, {"family": "Maqdissi", "given": "Joseph Agi", "initials": "JA"}, {"family": "Kaczmarczyk", "given": "Lech", "initials": "L", "orcid": "0000-0003-2747-3134", "researcher": {"href": "https://publications.scilifelab.se/researcher/2b192685d0c2438497741e66bfc183c9.json"}}, {"family": "Zijlstra", "given": "Jente J", "initials": "JJ"}, {"family": "Faketija", "given": "Matej", "initials": "M"}, {"family": "Perkins", "given": "Matthew", "initials": "M"}, {"family": "Paul", "given": "Gesine", "initials": "G", "orcid": "0000-0002-6806-2254", "researcher": {"href": "https://publications.scilifelab.se/researcher/dbbb29ff13af4e28afddbf78764cad29.json"}}, {"family": "Hallbeck", "given": "Martin", "initials": "M", "orcid": "0000-0001-6716-0314", "researcher": {"href": "https://publications.scilifelab.se/researcher/17f7b361871045a1b1e3cdfec9ebe5ec.json"}}, {"family": "Ingelsson", "given": "Martin", "initials": "M", "orcid": "0000-0001-5466-8370", "researcher": {"href": "https://publications.scilifelab.se/researcher/903a14004e794693bebb8c8ca345c626.json"}}, {"family": "Watts", "given": "Joel C", "initials": "JC"}, {"family": "Reichenbach", "given": "Nicole", "initials": "N"}, {"family": "Petzold", "given": "Gabor C", "initials": "GC", "orcid": "0000-0002-0145-8641", "researcher": {"href": "https://publications.scilifelab.se/researcher/0a64d37850384e10a8a4199ea81ae856.json"}}, {"family": "Schieweck", "given": "Rico", "initials": "R"}, {"family": "Heneka", "given": "Michael T", "initials": "MT", "orcid": "0000-0003-4996-1630", "researcher": {"href": "https://publications.scilifelab.se/researcher/8c46f161bc8544a78eef05ee0b74bb47.json"}}, {"family": "Jackson", "given": "Walker S", "initials": "WS", "orcid": "0000-0002-3003-5509", "researcher": {"href": "https://publications.scilifelab.se/researcher/62f49c7978954d098514c5b1bfa9e34b.json"}}], "type": "journal-article", "published": "2026-05-06", "journal": {"title": "Brain", "issn": "0006-8950", "issn-l": null}, "abstract": "Neuroinflammation, particularly that involving reactive microglia, the brain's resident immune cells, is implicated in the pathogenesis of major neurodegenerative diseases (NDs). Multiple studies have reported changes in ribosomal protein (RP) expression during neurodegeneration, but the significance of these changes remains unclear. Ribosomes are evolutionarily conserved protein-synthesizing machines, and although commonly viewed as invariant, accumulating evidence suggests functional ribosome specialization through variation in their protein composition. Among RPs, S24, encoded by RPS24 in humans and Rps24 in mice, is unique as its transcripts undergo alternative splicing to produce protein variants with different C-terminal sequences that are differentially expressed across tissues and cell types. Understanding heterogeneous RP expression patterns across brain regions and cell types could reveal mechanisms underlying selective vulnerability in NDs and provide new biomarkers for neuroinflammatory responses. To identify RP expression patterns across brain regions in neurons, astrocytes, and microglia we analyzed cell type-specific translating mRNAs from mice. To investigate Rps24 isoform-specific expression, we performed cell type-resolved transcript analysis and developed antibodies specific for the S24-PKE protein variant encoded by mRNA isoform Rps24c. We examined Rps24c/S24-PKE expression in brains from mouse models of aging and neurodegeneration, as well as in human postmortem tissue from patients with Alzheimer's disease (AD), Parkinson's disease (PD), and Huntington's disease (HD). This work revealed distinct RP expression patterns across brain regions and between neurons, astrocytes, and microglia, including neuron-enriched RPs Rpl13a and Rps10. Analysis of RP paralogs revealed complex expression relationships with their canonical counterparts, suggesting regulated mechanisms for generating heterogeneous ribosomes. Across brain regions and cell types, Rplp0 and Rpl13a, commonly used normalization references, showed heterogeneous expression, raising important methodological considerations for gene expression studies. Rps24 isoforms exhibited striking cell type-specific expression patterns. Rps24c was predominantly expressed in microglia and was increased by neuroinflammation caused by aging, neurodegeneration, or inflammatory chemicals. Using S24-PKE-specific antibodies, we verified increased expression of this protein variant in brains with AD, PD, and HD, and in relevant mouse models. These findings establish heterogeneous RP expression as a feature of brain cell types which may enable cell type-specific translation regulation via specialized ribosomes. This work also identifies Rps24c/S24-PKE as a potential novel marker for neuroinflammation and neurodegeneration and provides new tools for monitoring these responses.", "doi": "10.1093/brain/awag166", "pmid": "42087813", "labels": {"NGI Short read": "Service", "NGI Stockholm (Genomics Production)": "Service", "National Genomics Infrastructure": "Service"}, "xrefs": [{"db": "pii", "key": "8670210"}], "notes": [], "created": "2026-05-11T12:23:19.422Z", "modified": "2026-07-10T08:27:01.238Z"}, {"entity": "publication", "iuid": "859055d5fe394252bb2808f0d2a3394e", "links": {"self": {"href": "https://publications.scilifelab.se/publication/859055d5fe394252bb2808f0d2a3394e.json"}, "display": {"href": "https://publications.scilifelab.se/publication/859055d5fe394252bb2808f0d2a3394e"}}, "title": "ATP1A3 dysfunction causes motor hyperexcitability and afterhyperpolarization loss in a dystonia model.", "authors": [{"family": "Akkuratov", "given": "Evgeny E", "initials": "EE"}, {"family": "Sorrell", "given": "Francesca", "initials": "F"}, {"family": "Picton", "given": "Laurence D", "initials": "LD"}, {"family": "Sousa", "given": "Vasco C", "initials": "VC"}, {"family": "Paucar", "given": "Martin", "initials": "M", "orcid": "0000-0003-3735-1480", "researcher": {"href": "https://publications.scilifelab.se/researcher/bbc592904eb5402ea48a624471d4b939.json"}}, {"family": "Jans", "given": "Daniel", "initials": "D", "orcid": "0000-0002-6356-9742", "researcher": {"href": "https://publications.scilifelab.se/researcher/fe197a6a51a946a7a6c01f4c9c6cce08.json"}}, {"family": "Svensson", "given": "Lill-Britt", "initials": "LB"}, {"family": "Lindskog", "given": "Maria", "initials": "M", "orcid": "0000-0001-9484-1983", "researcher": {"href": "https://publications.scilifelab.se/researcher/1592b4e2f1354bdd8b35f384dcac78c2.json"}}, {"family": "Fritz", "given": "Nicolas", "initials": "N", "orcid": "0000-0002-9722-7425", "researcher": {"href": "https://publications.scilifelab.se/researcher/ec61383c813443f29dea569ea935b284.json"}}, {"family": "Liebmann", "given": "Thomas", "initials": "T"}, {"family": "Sillar", "given": "Keith T", "initials": "KT"}, {"family": "Rosewich", "given": "Hendrik", "initials": "H", "orcid": "0000-0003-4692-5511", "researcher": {"href": "https://publications.scilifelab.se/researcher/fffad5ec5d2d48a78573e71d7ba3c2dd.json"}}, {"family": "Svenningsson", "given": "Per", "initials": "P", "orcid": "0000-0001-6727-3802", "researcher": {"href": "https://publications.scilifelab.se/researcher/5199496295334771ba3c5621a83a6f43.json"}}, {"family": "Brismar", "given": "Hjalmar", "initials": "H", "orcid": "0000-0003-0578-4003", "researcher": {"href": "https://publications.scilifelab.se/researcher/1ec23336e2ef4e298f340876f1136dce.json"}}, {"family": "Miles", "given": "Gareth B", "initials": "GB"}, {"family": "Aperia", "given": "Anita", "initials": "A"}], "type": "journal article", "published": "2025-04-03", "journal": {"title": "Brain", "issn": "1460-2156", "volume": "148", "issue": "4", "pages": "1099-1105", "issn-l": "0006-8950"}, "abstract": "Mutations in the gene encoding the alpha3 Na+/K+-ATPase isoform (ATP1A3) lead to movement disorders that manifest with dystonia, a common neurological symptom with many different origins, but for which the underlying molecular mechanisms remain poorly understood. We have generated an ATP1A3 mutant mouse that displays motor impairments and a hyperexcitable motor phenotype compatible with dystonia. We show that neurons harbouring this mutation are compromised in their ability to extrude raised levels of intracellular sodium, highlighting a profound deficit in neuronal sodium homeostasis. We show that the spinal motor network in ATP1A3 mutant mice has a reduced responsiveness to activity-dependent rises in intracellular sodium and that this is accompanied by loss of the Na+/K+-ATPase-mediated afterhyperpolarization in motor neurons. Taken together, our data support that the alpha3 Na+/K+-ATPase is important for cellular and spinal motor network homeostasis. These insights suggest that it may be useful to consider ways to compensate for this loss of a critical afterhyperpolarization-dependent control of neuronal excitability when developing future therapies for dystonia.", "doi": "10.1093/brain/awae373", "pmid": "39533828", "labels": {"Integrated Microscopy Technologies Stockholm": "Service"}, "xrefs": [{"db": "pmc", "key": "PMC11967811"}, {"db": "pii", "key": "7896743"}], "notes": [], "created": "2024-11-18T09:02:43.236Z", "modified": "2025-11-12T11:33:48.972Z"}, {"entity": "publication", "iuid": "440f5696bfa547d1a980211f91a257d9", "links": {"self": {"href": "https://publications.scilifelab.se/publication/440f5696bfa547d1a980211f91a257d9.json"}, "display": {"href": "https://publications.scilifelab.se/publication/440f5696bfa547d1a980211f91a257d9"}}, "title": "Inhibiting metabotropic glutamate receptor 5 after stroke restores brain function and connectivity.", "authors": [{"family": "Hakon", "given": "Jakob", "initials": "J"}, {"family": "Quattromani", "given": "Miriana J", "initials": "MJ"}, {"family": "Sj\u00f6lund", "given": "Carin", "initials": "C"}, {"family": "Talhada", "given": "Daniela", "initials": "D"}, {"family": "Kim", "given": "Bungchan", "initials": "B"}, {"family": "Moyanova", "given": "Slavianka", "initials": "S"}, {"family": "Mastroiacovo", "given": "Federica", "initials": "F"}, {"family": "Di Menna", "given": "Luisa", "initials": "L"}, {"family": "Olsson", "given": "Roger", "initials": "R"}, {"family": "Englund", "given": "Elisabet", "initials": "E"}, {"family": "Nicoletti", "given": "Ferdinando", "initials": "F"}, {"family": "Ruscher", "given": "Karsten", "initials": "K"}, {"family": "Bauer", "given": "Adam Q", "initials": "AQ"}, {"family": "Wieloch", "given": "Tadeusz", "initials": "T", "orcid": "0000-0002-7669-2520", "researcher": {"href": "https://publications.scilifelab.se/researcher/503d7a0ebc1d4028bdad470ef483b937.json"}}], "type": "journal article", "published": "2023-09-01", "journal": {"title": "Brain", "issn": "1460-2156", "issn-l": "0006-8950"}, "abstract": "Stroke results in local neural disconnection and brain-wide neuronal network dysfunction leading to neurological deficits. Beyond the hyper-acute phase of ischemic stroke, there is no clinically-approved pharmacological treatment that alleviates sensorimotor impairments. Functional recovery after stroke involves the formation of new or alternative neuronal circuits including existing neural connections. The type-5 metabotropic glutamate receptor (mGluR5) has been shown to modulate brain plasticity and function, and is a therapeutic target in neurological diseases outside of stroke. We investigated whether mGluR5 influences functional recovery and network reorganization rodent models of focal ischemia. Using multiple behavioral tests we observed that treatment with negative allosteric modulators (NAMs) of mGluR5 (MTEP, fenobam, and AFQ056) for 12 days, starting 2 or 10 days after stroke, restored lost sensorimotor functions, without diminishing infarct size. Recovery was evident within hours after initiation of treatment and progressed over the subsequent 12 days. Recovery was prevented by activation of mGluR5 with the positive allosteric modulator VU0360172, and accelerated in mGluR5 KO mice compared to wild-type mice. After stroke, multisensory stimulation by enriched environments (EE) enhanced recovery, a result prevented by VU0360172, implying a role of mGluR5 in EE-mediated recovery. Additionally, MTEP treatment in conjunction with EE housing provided an additive recovery enhancement compared to either MTEP or EE alone. Using optical intrinsic signal imaging, we observed brain-wide disruptions in resting-state functional connectivity after stroke that were prevented by mGluR5 inhibition in distinct areas of contralesional sensorimotor and bilateral visual cortices. The levels of mGluR5 protein in mice and in tissue samples of stroke patients were unchanged after stroke. We conclude that neuronal circuitry subserving sensorimotor function after stroke is depressed by a mGluR5-dependent maladaptive plasticity mechanism that can be restored by mGluR5 inhibition. Post-acute stroke treatment with mGluR5 NAMs combined with rehabilitative training may represent a novel post-acute stroke therapy.", "doi": "10.1093/brain/awad293", "pmid": "37656990", "labels": {"Chemical Biology Consortium Sweden": "Collaborative"}, "xrefs": [{"db": "pii", "key": "7258740"}], "notes": [], "created": "2023-11-24T11:39:09.729Z", "modified": "2025-10-17T13:04:27.567Z"}, {"entity": "publication", "iuid": "cd17e9ab041c404ca1809ccf976223c1", "links": {"self": {"href": "https://publications.scilifelab.se/publication/cd17e9ab041c404ca1809ccf976223c1.json"}, "display": {"href": "https://publications.scilifelab.se/publication/cd17e9ab041c404ca1809ccf976223c1"}}, "title": "Distinct subcellular autophagy impairments in induced neurons from patients with Huntington's disease.", "authors": [{"family": "Pircs", "given": "Karolina", "initials": "K", "orcid": "0000-0001-8281-4785", "researcher": {"href": "https://publications.scilifelab.se/researcher/070f9eb7abde403697f7e8ba0f9ac40e.json"}}, {"family": "Drouin-Ouellet", "given": "Janelle", "initials": "J"}, {"family": "Horv\u00e1th", "given": "Vivien", "initials": "V"}, {"family": "Gil", "given": "Jeovanis", "initials": "J"}, {"family": "Rezeli", "given": "Melinda", "initials": "M"}, {"family": "Garza", "given": "Raquel", "initials": "R"}, {"family": "Grassi", "given": "Daniela A", "initials": "DA"}, {"family": "Sharma", "given": "Yogita", "initials": "Y"}, {"family": "St-Amour", "given": "Isabelle", "initials": "I"}, {"family": "Harris", "given": "Kate", "initials": "K"}, {"family": "J\u00f6nsson", "given": "Marie E", "initials": "ME"}, {"family": "Johansson", "given": "Pia A", "initials": "PA"}, {"family": "Vuono", "given": "Romina", "initials": "R"}, {"family": "Fazal", "given": "Shaline V", "initials": "SV"}, {"family": "Stoker", "given": "Thomas", "initials": "T"}, {"family": "Hersbach", "given": "Bob A", "initials": "BA"}, {"family": "Sharma", "given": "Kritika", "initials": "K"}, {"family": "Lagerwall", "given": "Jessica", "initials": "J"}, {"family": "Lagerstr\u00f6m", "given": "Stina", "initials": "S"}, {"family": "Storm", "given": "Petter", "initials": "P"}, {"family": "H\u00e9bert", "given": "S\u00e9bastien S", "initials": "SS"}, {"family": "Marko-Varga", "given": "Gy\u00f6rgy", "initials": "G"}, {"family": "Parmar", "given": "Malin", "initials": "M"}, {"family": "Barker", "given": "Roger A", "initials": "RA"}, {"family": "Jakobsson", "given": "Johan", "initials": "J", "orcid": "0000-0003-0669-7673", "researcher": {"href": "https://publications.scilifelab.se/researcher/1b08f33ec79b4a36a5f62223d7174201.json"}}], "type": "journal article", "published": "2022-09-14", "journal": {"title": "Brain", "issn": "1460-2156", "volume": "145", "issue": "9", "pages": "3035-3057", "issn-l": "0006-8950"}, "abstract": "Huntington's disease is a neurodegenerative disorder caused by CAG expansions in the huntingtin (HTT) gene. Modelling Huntington's disease is challenging, as rodent and cellular models poorly recapitulate the disease as seen in ageing humans. To address this, we generated induced neurons through direct reprogramming of human skin fibroblasts, which retain age-dependent epigenetic characteristics. Huntington's disease induced neurons (HD-iNs) displayed profound deficits in autophagy, characterized by reduced transport of late autophagic structures from the neurites to the soma. These neurite-specific alterations in autophagy resulted in shorter, thinner and fewer neurites specifically in HD-iNs. CRISPRi-mediated silencing of HTT did not rescue this phenotype but rather resulted in additional autophagy alterations in control induced neurons, highlighting the importance of wild-type HTT in normal neuronal autophagy. In summary, our work identifies a distinct subcellular autophagy impairment in adult patient derived Huntington's disease neurons and provides a new rationale for future development of autophagy activation therapies.", "doi": "10.1093/brain/awab473", "pmid": "34936701", "labels": {"Clinical Genomics Lund": "Service", "Clinical Genomics": "Service"}, "xrefs": [{"db": "pii", "key": "6479694"}, {"db": "pmc", "key": "PMC9473361"}], "notes": [], "created": "2022-11-17T08:32:41.877Z", "modified": "2022-11-17T08:32:42.006Z"}, {"entity": "publication", "iuid": "ab68cafc60d9492f9a0dd5ac2b1247ca", "links": {"self": {"href": "https://publications.scilifelab.se/publication/ab68cafc60d9492f9a0dd5ac2b1247ca.json"}, "display": {"href": "https://publications.scilifelab.se/publication/ab68cafc60d9492f9a0dd5ac2b1247ca"}}, "title": "ATP6V0C variants impair vacuolar V-ATPase causing a neurodevelopmental disorder often associated with epilepsy.", "authors": [{"family": "Mattison", "given": "Kari A", "initials": "KA", "orcid": "0000-0003-2130-5228", "researcher": {"href": "https://publications.scilifelab.se/researcher/f0ab721860a74b7ab01729ac00073486.json"}}, {"family": "Tossing", "given": "Gilles", "initials": "G"}, {"family": "Mulroe", "given": "Fred", "initials": "F"}, {"family": "Simmons", "given": "Callum", "initials": "C"}, {"family": "Butler", "given": "Kameryn M", "initials": "KM"}, {"family": "Schreiber", "given": "Alison", "initials": "A"}, {"family": "Alsadah", "given": "Adnan", "initials": "A"}, {"family": "Neilson", "given": "Derek E", "initials": "DE"}, {"family": "Naess", "given": "Karin", "initials": "K"}, {"family": "Wedell", "given": "Anna", "initials": "A"}, {"family": "Wredenberg", "given": "Anna", "initials": "A"}, {"family": "Sorlin", "given": "Arthur", "initials": "A"}, {"family": "McCann", "given": "Emma", "initials": "E"}, {"family": "Burghel", "given": "George J", "initials": "GJ"}, {"family": "Menendez", "given": "Beatriz", "initials": "B"}, {"family": "Hoganson", "given": "George E", "initials": "GE"}, {"family": "Botto", "given": "Lorenzo D", "initials": "LD"}, {"family": "Filloux", "given": "Francis M", "initials": "FM"}, {"family": "Aledo-Serrano", "given": "\u00c1ngel", "initials": "\u00c1"}, {"family": "Gil-Nagel", "given": "Antonio", "initials": "A"}, {"family": "Tatton-Brown", "given": "Katrina", "initials": "K"}, {"family": "Verbeek", "given": "Nienke E", "initials": "NE"}, {"family": "van Hirtum-Das", "given": "Michele", "initials": "M"}, {"family": "Breckpot", "given": "Jeroen", "initials": "J"}, {"family": "Hammer", "given": "Trine Bj\u00f8rg", "initials": "TB"}, {"family": "M\u00f8ller", "given": "Rikke S", "initials": "RS"}, {"family": "Whitney", "given": "Andrea", "initials": "A"}, {"family": "Douglas", "given": "Andrew G L", "initials": "AGL"}, {"family": "Kharbanda", "given": "Mira", "initials": "M"}, {"family": "Brunetti-Pierri", "given": "Nicola", "initials": "N", "orcid": "0000-0002-6895-8819", "researcher": {"href": "https://publications.scilifelab.se/researcher/c9785f9985d645259283e808cdcd77a9.json"}}, {"family": "Morleo", "given": "Manuela", "initials": "M"}, {"family": "Nigro", "given": "Vincenzo", "initials": "V", "orcid": "0000-0002-3378-5006", "researcher": {"href": "https://publications.scilifelab.se/researcher/878ef24a4e4c4fc1aea632c8738b4321.json"}}, {"family": "May", "given": "Halie J", "initials": "HJ"}, {"family": "Tao", "given": "James X", "initials": "JX"}, {"family": "Argili", "given": "Emanuela", "initials": "E"}, {"family": "Sherr", "given": "Elliot H", "initials": "EH"}, {"family": "Dobyns", "given": "William B", "initials": "WB", "orcid": "0000-0002-7681-2844", "researcher": {"href": "https://publications.scilifelab.se/researcher/d24102c168b0425baaeb674247ae4076.json"}}, {"family": "Consortium", "given": "Genomics England Research", "initials": "GER"}, {"family": "Baines", "given": "Richard A", "initials": "RA", "orcid": "0000-0001-8571-4376", "researcher": {"href": "https://publications.scilifelab.se/researcher/e97fd3695c4540c9a5db676da48a3fda.json"}}, {"family": "Warwicker", "given": "Jim", "initials": "J"}, {"family": "Parker", "given": "J Alex", "initials": "JA"}, {"family": "Banka", "given": "Siddharth", "initials": "S", "orcid": "0000-0002-8527-2210", "researcher": {"href": "https://publications.scilifelab.se/researcher/cf26463312a64914ba658ba461ab89c4.json"}}, {"family": "Campeau", "given": "Philippe M", "initials": "PM", "orcid": "0000-0002-0139-8239", "researcher": {"href": "https://publications.scilifelab.se/researcher/3e2ed42024554f40a944c4d507a6cabe.json"}}, {"family": "Escayg", "given": "Andrew", "initials": "A", "orcid": "0000-0001-9713-7107", "researcher": {"href": "https://publications.scilifelab.se/researcher/c1419b4eb2e5454ba1cf8cb65b3578d2.json"}}], "type": "journal article", "published": "2022-09-08", "journal": {"title": "Brain", "issn": "1460-2156", "issn-l": "0006-8950"}, "abstract": "The vacuolar H+-ATPase (V-ATPase) is an enzymatic complex that functions in an ATP-dependent manner to pump protons across membranes and acidify organelles, thereby creating the proton/pH gradient required for membrane trafficking by several different types of transporters. We describe heterozygous point variants in ATP6V0C, encoding the c-subunit in the membrane bound integral domain of the V-ATPase, in 27 patients with neurodevelopmental abnormalities with or without epilepsy. Corpus callosum hypoplasia and cardiac abnormalities were also present in some patients. In silico modeling suggested that the patient variants interfere with the interactions between the ATP6V0C and ATP6V0A subunits during ATP hydrolysis. Consistent with decreased V-ATPase activity, functional analyses conducted in Saccharomyces cerevisiae revealed reduced LysoSensor fluorescence and reduced growth in media containing varying concentrations of CaCl2. Knockdown of ATP6V0C in Drosophila resulted in increased duration of seizure-like behavior, and the expression of selected patient variants in Caenorhabditis elegans led to reduced growth, motor dysfunction, and reduced lifespan. In summary, this study establishes ATP6V0C as an important disease gene, describes the clinical features of the associated neurodevelopmental disorder, and provides insight into disease mechanisms.", "doi": "10.1093/brain/awac330", "pmid": "36074901", "labels": {"Clinical Genomics Stockholm": "Service", "Clinical Genomics": "Service"}, "xrefs": [{"db": "pii", "key": "6694191"}], "notes": [], "created": "2022-11-22T07:33:52.940Z", "modified": "2022-11-22T07:33:53.186Z"}, {"entity": "publication", "iuid": "b663df15bfdf4bfcacc56407fda3cb8a", "links": {"self": {"href": "https://publications.scilifelab.se/publication/b663df15bfdf4bfcacc56407fda3cb8a.json"}, "display": {"href": "https://publications.scilifelab.se/publication/b663df15bfdf4bfcacc56407fda3cb8a"}}, "title": "Complement peptide C3a stimulates neural plasticity after experimental brain ischaemia.", "authors": [{"family": "Stokowska", "given": "Anna", "initials": "A"}, {"family": "Atkins", "given": "Alison L", "initials": "AL"}, {"family": "Mor\u00e1n", "given": "Javier", "initials": "J"}, {"family": "Pekny", "given": "Tulen", "initials": "T"}, {"family": "Bulmer", "given": "Linda", "initials": "L"}, {"family": "Pascoe", "given": "Michaela C", "initials": "MC"}, {"family": "Barnum", "given": "Scott R", "initials": "SR"}, {"family": "Wetsel", "given": "Rick A", "initials": "RA"}, {"family": "Nilsson", "given": "Jonas A", "initials": "JA"}, {"family": "Dragunow", "given": "Mike", "initials": "M"}, {"family": "Pekna", "given": "Marcela", "initials": "M"}], "type": "journal article", "published": "2017-02-00", "journal": {"title": "Brain", "issn": "1460-2156", "volume": "140", "issue": "2", "pages": "353-369", "issn-l": "0006-8950"}, "abstract": "Ischaemic stroke induces endogenous repair processes that include proliferation and differentiation of neural stem cells and extensive rewiring of the remaining neural connections, yet about 50% of stroke survivors live with severe long-term disability. There is an unmet need for drug therapies to improve recovery by promoting brain plasticity in the subacute to chronic phase after ischaemic stroke. We previously showed that complement-derived peptide C3a regulates neural progenitor cell migration and differentiation in vitro and that C3a receptor signalling stimulates neurogenesis in unchallenged adult mice. To determine the role of C3a-C3a receptor signalling in ischaemia-induced neural plasticity, we subjected C3a receptor-deficient mice, GFAP-C3a transgenic mice expressing biologically active C3a in the central nervous system, and their respective wild-type controls to photothrombotic stroke. We found that C3a overexpression increased, whereas C3a receptor deficiency decreased post-stroke expression of GAP43 (P < 0.01), a marker of axonal sprouting and plasticity, in the peri-infarct cortex. To verify the translational potential of these findings, we used a pharmacological approach. Daily intranasal treatment of wild-type mice with C3a beginning 7 days after stroke induction robustly increased synaptic density (P < 0.01) and expression of GAP43 in peri-infarct cortex (P < 0.05). Importantly, the C3a treatment led to faster and more complete recovery of forepaw motor function (P < 0.05). We conclude that C3a-C3a receptor signalling stimulates post-ischaemic neural plasticity and intranasal treatment with C3a receptor agonists is an attractive approach to improve functional recovery after ischaemic brain injury.", "doi": "10.1093/brain/aww314", "pmid": "27956400", "labels": {"Integrated Microscopy Technologies Gothenburg": "Service"}, "xrefs": [{"db": "pii", "key": "aww314"}], "notes": [], "created": "2020-01-23T16:36:17.901Z", "modified": "2021-06-21T15:43:36.124Z"}], "created": "2020-01-23T16:36:17.917Z", "modified": "2020-11-27T13:14:02.923Z"}