{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,6,19]],"date-time":"2026-06-19T03:35:09Z","timestamp":1781840109572,"version":"3.54.5"},"reference-count":214,"publisher":"MDPI AG","issue":"8","license":[{"start":{"date-parts":[[2024,4,11]],"date-time":"2024-04-11T00:00:00Z","timestamp":1712793600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Kazan Federal University Strategic Academic Leadership Program","award":["PRIORITY-2030"],"award-info":[{"award-number":["PRIORITY-2030"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>Perineuronal nets (PNN) are a special highly structured type of extracellular matrix encapsulating synapses on large populations of CNS neurons. PNN undergo structural changes in schizophrenia, epilepsy, Alzheimer\u2019s disease, stroke, post-traumatic conditions, and some other brain disorders. The functional role of the PNN microstructure in brain pathologies has remained largely unstudied until recently. Here, we review recent research implicating PNN microstructural changes in schizophrenia and other disorders. We further concentrate on high-resolution studies of the PNN mesh units surrounding synaptic boutons to elucidate fine structural details behind the mutual functional regulation between the ECM and the synaptic terminal. We also review some updates regarding PNN as a potential pharmacological target. Artificial intelligence (AI)-based methods are now arriving as a new tool that may have the potential to grasp the brain\u2019s complexity through a wide range of organization levels\u2014from synaptic molecular events to large scale tissue rearrangements and the whole-brain connectome function. This scope matches exactly the complex role of PNN in brain physiology and pathology processes, and the first AI-assisted PNN microscopy studies have been reported. To that end, we report here on a machine learning-assisted tool for PNN mesh contour tracing.<\/jats:p>","DOI":"10.3390\/ijms25084227","type":"journal-article","created":{"date-parts":[[2024,4,11]],"date-time":"2024-04-11T07:09:28Z","timestamp":1712819368000},"page":"4227","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":6,"title":["Perineuronal Net Microscopy: From Brain Pathology to Artificial Intelligence"],"prefix":"10.3390","volume":"25","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-2905-2272","authenticated-orcid":false,"given":"Mikhail","family":"Paveliev","sequence":"first","affiliation":[{"name":"Neuroscience Center, University of Helsinki, Haartmaninkatu 8, 00290 Helsinki, Finland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Anton A.","family":"Egorchev","sequence":"additional","affiliation":[{"name":"Institute of Computational Mathematics and Information Technologies, Kazan Federal University, Kremlyovskaya 35, Kazan 420008, Tatarstan, Russia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Foat","family":"Musin","sequence":"additional","affiliation":[{"name":"Institute of Computational Mathematics and Information Technologies, Kazan Federal University, Kremlyovskaya 35, Kazan 420008, Tatarstan, Russia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5145-7532","authenticated-orcid":false,"given":"Nikita","family":"Lipachev","sequence":"additional","affiliation":[{"name":"Institute of Physics, Kazan Federal University, Kremlyovskaya 16a, Kazan 420008, Tatarstan, Russia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7686-1075","authenticated-orcid":false,"given":"Anastasiia","family":"Melnikova","sequence":"additional","affiliation":[{"name":"Institute of Fundamental Medicine and Biology, Kazan Federal University, Karl Marx 74, Kazan 420015, Tatarstan, Russia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Rustem M.","family":"Gimadutdinov","sequence":"additional","affiliation":[{"name":"Institute of Computational Mathematics and Information Technologies, Kazan Federal University, Kremlyovskaya 35, Kazan 420008, Tatarstan, Russia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Aidar R.","family":"Kashipov","sequence":"additional","affiliation":[{"name":"Institute of Artificial Intelligence, Robotics and Systems Engineering, Kazan Federal University, Kremlyovskaya 18, Kazan 420008, Tatarstan, Russia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Dmitry","family":"Molotkov","sequence":"additional","affiliation":[{"name":"Biomedicum Imaging Unit, University of Helsinki, Haartmaninkatu 8, 00014 Helsinki, Finland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Dmitry E.","family":"Chickrin","sequence":"additional","affiliation":[{"name":"Institute of Artificial Intelligence, Robotics and Systems Engineering, Kazan Federal University, Kremlyovskaya 18, Kazan 420008, Tatarstan, Russia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Albert V.","family":"Aganov","sequence":"additional","affiliation":[{"name":"Institute of Physics, Kazan Federal University, Kremlyovskaya 16a, Kazan 420008, Tatarstan, Russia"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2024,4,11]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"451","DOI":"10.1038\/s41583-019-0196-3","article-title":"The roles of perineuronal nets and the perinodal extracellular matrix in neuronal function","volume":"20","author":"Fawcett","year":"2019","journal-title":"Nat. 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