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So public microarray data of hippocampal homogenates from (healthy) young, (healthy) elder and elder with mild cognitive impairment (MCI) were subjected to re\u2010analysis by a multi\u2010step computational pipeline. Ontologies and pathway analyses were compared after determining the differential genes that, belonging to astrocytes, have splice forms. Likewise, the subset of molecules exportable to exosomes was also determined. The results showed that astrocyte's phenotypes changed significantly. While already \u2018activated\u2019 astrocytes were found in the younger group, major changes occurred during ageing (increased vascular remodelling and response to mechanical stimulus, diminished long\u2010term potentiation and increased long\u2010term depression). MCI's astrocytes showed some \u2018rejuvenated\u2019 features, but their sensitivity to shear stress was markedly lost. Importantly, most of the changes showed to be sex biassed. Men's astrocytes are enriched in a type \u2018endfeet\u2010astrocytome\u2019, whereas women's astrocytes appear close to the \u2018scar\u2010forming\u2019 type (prone to endothelial dysfunction, hypercholesterolemia, loss of glutamatergic synapses, Ca\n                    <jats:sup>+2<\/jats:sup>\n                    dysregulation, hypoxia, oxidative stress and \u2018pro\u2010coagulant\u2019 phenotype). In conclusion, the computational dissection of the networks based on the hippocampal gene isoforms provides a relevant proxy to in vivo astrocytes, also revealing the occurrence of sexual differences. Analyses of the astrocytic exosomes did not provide an acceptable approximation to the overall functioning of astrocytes in the hippocampus, probably due to the selective cellular mechanisms which charge the cargo molecules.\n                  <\/jats:p>","DOI":"10.1111\/ejn.16081","type":"journal-article","created":{"date-parts":[[2023,7,10]],"date-time":"2023-07-10T07:07:34Z","timestamp":1688972854000},"page":"2677-2707","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":7,"title":["Human hippocampal astrocytes: Computational dissection of their transcriptome, sexual differences and exosomes across ageing and mild\u2010cognitive impairment"],"prefix":"10.1111","volume":"58","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-9878-5904","authenticated-orcid":false,"given":"Daniel V.","family":"Guebel","sequence":"first","affiliation":[{"name":"Biotechnology Counseling Services  Buenos Aires 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