{"entity": "journal", "iuid": "5b5435326e464aa0a2a40cf167aee379", "timestamp": "2026-07-19T19:25:33.012Z", "links": {"self": {"href": "https://publications.scilifelab.se/journal/Front%20Aging%20Neurosci.json"}, "display": {"href": "https://publications.scilifelab.se/journal/Front%20Aging%20Neurosci"}}, "title": "Front Aging Neurosci", "issn": "1663-4365", "issn-l": null, "publications_count": 3, "publications": [{"entity": "publication", "iuid": "d4450142a100484a9f16e92b92dc78ee", "links": {"self": {"href": "https://publications.scilifelab.se/publication/d4450142a100484a9f16e92b92dc78ee.json"}, "display": {"href": "https://publications.scilifelab.se/publication/d4450142a100484a9f16e92b92dc78ee"}}, "title": "Nigral transcriptomic profiles in Engrailed-1 hemizygous mouse models of Parkinson's disease reveal upregulation of oxidative phosphorylation-related genes associated with delayed dopaminergic neurodegeneration.", "authors": [{"family": "Belfiori", "given": "Lautaro Francisco", "initials": "LF"}, {"family": "Due\u00f1as Rey", "given": "Alfredo", "initials": "A"}, {"family": "Ralbovszki", "given": "Dorottya M\u00e1ria", "initials": "DM"}, {"family": "Jimenez-Ferrer", "given": "Itzia", "initials": "I"}, {"family": "Fredlund", "given": "Filip", "initials": "F"}, {"family": "Balikai", "given": "Sagar Shivayogi", "initials": "SS"}, {"family": "Ahr\u00e9n", "given": "Dag", "initials": "D"}, {"family": "Brolin", "given": "Kajsa Atterling", "initials": "KA"}, {"family": "Swanberg", "given": "Maria", "initials": "M"}], "type": "journal article", "published": "2024-02-05", "journal": {"title": "Front Aging Neurosci", "issn": "1663-4365", "volume": "16", "pages": "1337365", "issn-l": null}, "abstract": "Parkinson's disease (PD) is the second most common neurodegenerative disorder, increasing both in terms of prevalence and incidence. To date, only symptomatic treatment is available, highlighting the need to increase knowledge on disease etiology in order to develop new therapeutic strategies. Hemizygosity for the gene Engrailed-1 (En1), encoding a conserved transcription factor essential for the programming, survival, and maintenance of midbrain dopaminergic neurons, leads to progressive nigrostriatal degeneration, motor impairment and depressive-like behavior in SwissOF1 (OF1-En1+/-). The neurodegenerative phenotype is, however, absent in C57Bl/6j (C57-En1+/-) mice. En1+/- mice are thus highly relevant tools to identify genetic factors underlying PD susceptibility.\n\nTranscriptome profiles were defined by RNAseq in microdissected substantia nigra from 1-week old OF1, OF1- En1+/-, C57 and C57- En1+/- male mice. Differentially expressed genes (DEGs) were analyzed for functional enrichment. Neurodegeneration was assessed in 4- and 16-week old mice by histology.\n\nNigrostriatal neurodegeneration was manifested in OF1- En1+/- mice by increased dopaminergic striatal axonal swellings from 4 to 16 weeks and decreased number of dopaminergic neurons in the SNpc at 16 weeks compared to OF1. In contrast, C57- En1+/- mice had no significant increase in axonal swellings or cell loss in SNpc at 16 weeks. Transcriptomic analyses identified 198 DEGs between OF1- En1+/- and OF1 mice but only 52 DEGs between C57- En1+/- and C57 mice. Enrichment analysis of DEGs revealed that the neuroprotective phenotype of C57- En1+/- mice was associated with a higher expression of oxidative phosphorylation-related genes compared to both C57 and OF1- En1+/- mice.\n\nOur results suggest that increased expression of genes encoding mitochondrial proteins before the onset of neurodegeneration is associated with increased resistance to PD-like nigrostriatal neurodegeneration. This highlights the importance of genetic background in PD models, how different strains can be used to model clinical and sub-clinical pathologies and provides insights to gene expression mechanisms associated with PD susceptibility and progression.", "doi": "10.3389/fnagi.2024.1337365", "pmid": "38374883", "labels": {"Bioinformatics Support, Infrastructure and Training": "Collaborative", "Bioinformatics Support and Infrastructure": "Collaborative", "Bioinformatics (NBIS)": "Collaborative"}, "xrefs": [{"db": "pmc", "key": "PMC10875038"}], "notes": [], "created": "2024-11-15T09:43:32.556Z", "modified": "2024-11-15T11:51:27.191Z"}, {"entity": "publication", "iuid": "c60765ceff1543019357336d394b7d5a", "links": {"self": {"href": "https://publications.scilifelab.se/publication/c60765ceff1543019357336d394b7d5a.json"}, "display": {"href": "https://publications.scilifelab.se/publication/c60765ceff1543019357336d394b7d5a"}}, "title": "Epigenetic clock indicates accelerated aging in glial cells of progressive multiple sclerosis patients.", "authors": [{"family": "Kular", "given": "Lara", "initials": "L"}, {"family": "Klose", "given": "Dennis", "initials": "D"}, {"family": "Urd\u00e1noz-Casado", "given": "Amaya", "initials": "A"}, {"family": "Ewing", "given": "Ewoud", "initials": "E"}, {"family": "Planell", "given": "Nuria", "initials": "N"}, {"family": "Gomez-Cabrero", "given": "David", "initials": "D"}, {"family": "Needhamsen", "given": "Maria", "initials": "M"}, {"family": "Jagodic", "given": "Maja", "initials": "M"}], "type": "journal article", "published": "2022-08-24", "journal": {"title": "Front Aging Neurosci", "issn": "1663-4365", "volume": "14", "pages": "926468", "issn-l": null}, "abstract": "Multiple sclerosis (MS) is a chronic inflammatory neurodegenerative disease of the central nervous system (CNS) characterized by irreversible disability at later progressive stages. A growing body of evidence suggests that disease progression depends on age and inflammation within the CNS. We aimed to investigate epigenetic aging in bulk brain tissue and sorted nuclei from MS patients using DNA methylation-based epigenetic clocks.\n\nWe applied Horvath's multi-tissue and Shireby's brain-specific Cortical clock on bulk brain tissue (n = 46), sorted neuronal (n = 54), and glial nuclei (n = 66) from post-mortem brain tissue of progressive MS patients and controls.\n\nWe found a significant increase in age acceleration residuals, corresponding to 3.6 years, in glial cells of MS patients compared to controls (P = 0.0024) using the Cortical clock, which held after adjustment for covariates (P = 0.0263). The 4.8-year age acceleration found in MS neurons ( adjP = 0.0054) did not withstand adjustment for covariates and no significant difference in age acceleration residuals was observed in bulk brain tissue between MS patients and controls.\n\nWhile the findings warrant replication in larger cohorts, our study suggests that glial cells of progressive MS patients exhibit accelerated biological aging.", "doi": "10.3389/fnagi.2022.926468", "pmid": "36092807", "labels": {"Bioinformatics Support for Computational Resources": "Service"}, "xrefs": [{"db": "pmc", "key": "PMC9454196"}], "notes": [], "created": "2022-11-09T15:54:26.824Z", "modified": "2024-01-16T13:48:35.110Z"}, {"entity": "publication", "iuid": "4637ca66aaac4fd0aab625b8c6355aad", "links": {"self": {"href": "https://publications.scilifelab.se/publication/4637ca66aaac4fd0aab625b8c6355aad.json"}, "display": {"href": "https://publications.scilifelab.se/publication/4637ca66aaac4fd0aab625b8c6355aad"}}, "title": "Deficits in Motor Performance, Neurotransmitters and Synaptic Plasticity in Elderly and Experimental Parkinsonian Mice Lacking GPR37.", "authors": [{"family": "Zhang", "given": "Xiaoqun", "initials": "X"}, {"family": "Mantas", "given": "Ioannis", "initials": "I"}, {"family": "Fridjonsdottir", "given": "Elva", "initials": "E"}, {"family": "Andr\u00e9n", "given": "Per E", "initials": "PE"}, {"family": "Chergui", "given": "Karima", "initials": "K"}, {"family": "Svenningsson", "given": "Per", "initials": "P"}], "type": "journal article", "published": "2020-03-27", "journal": {"title": "Front Aging Neurosci", "issn": "1663-4365", "volume": "12", "issue": null, "pages": "84", "issn-l": null}, "abstract": "Parkinson's disease (PD) etiology is attributed to aging and the progressive neurodegeneration of dopamine (DA) neurons of substantia nigra pars compacta (SNc). GPR37 is an orphan G-protein Coupled Receptor (GPCR) that is linked to the juvenile form of PD. In addition, misfolded GPR37 has been found in Lewy bodies. However, properly folded GPR37 found at the cell membrane appears to exert neuroprotection. In the present study we investigated the role of GPR37 in motor deficits due to aging or toxin-induced experimental parkinsonism. Elderly GPR37 knock out (KO) mice displayed hypolocomotion and worse fine movement performance compared to their WT counterparts. Striatal slice electrophysiology reveiled that GPR37 KO mice show profound decrease in long term potentiation (LTP) formation which is accompanied by an alteration in glutamate receptor subunit content. GPR37 KO animals exposed to intrastriatal 6-hydroxydopamine (6-OHDA) show poorer score in the behavioral cylinder test and more loss of the DA transporter (DAT) in striatum. The GPR37 KO striata exhibit a significant increase in GABA which is aggravated after DA depletion. Our data indicate that GPR37 KO mice have DA neuron deficit, enhanced striatal GABA levels and deficient corticostriatal LTP. They also respond stronger to 6-OHDA-induced neurotoxicity. Taken together, the data indicate that properly functional GPR37 may counteract aging processes and parkinsonism.", "doi": "10.3389/fnagi.2020.00084", "pmid": "32292338", "labels": {"Spatial Mass Spectrometry": "Collaborative"}, "xrefs": [{"db": "pmc", "key": "PMC7120535"}], "notes": [], "created": "2021-03-26T12:43:12.149Z", "modified": "2021-12-03T11:52:42.300Z"}], "created": "2021-03-26T12:43:12.165Z", "modified": "2021-03-26T12:43:12.165Z"}