{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,9,17]],"date-time":"2025-09-17T16:00:22Z","timestamp":1758124822615,"version":"3.41.2"},"reference-count":14,"publisher":"Wiley","issue":"9","license":[{"start":{"date-parts":[[2018,8,15]],"date-time":"2018-08-15T00:00:00Z","timestamp":1534291200000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["The Journal of Gene Medicine"],"published-print":{"date-parts":[[2018,9]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:sec><jats:title>Background<\/jats:title><jats:p>The trisynaptic circuit (<jats:ext-link xmlns:xlink=\"http:\/\/www.w3.org\/1999\/xlink\" xlink:href=\"https:\/\/en.wikipedia.org\/wiki\/Entorhinal_cortex\">entorhinal cortex<\/jats:ext-link>\u2013<jats:ext-link xmlns:xlink=\"http:\/\/www.w3.org\/1999\/xlink\" xlink:href=\"https:\/\/en.wikipedia.org\/wiki\/Dentate_gyrus\">dentate gyrus<\/jats:ext-link>\u2013CA3\u2013CA1) is a key unidirectional network in the hippocampus. Damage to the hippocampus interrupts this circuit and causes neurological disorders. Efficient delivery of therapeutic genes into this network is of great interest with respect to treating trisynaptic circuit pathologies.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>We generated a lentivector system pseudotyped by a variant of rabies glycoprotein, FUG\u2010B2. The efficiency of the vector in the retrograde transduction of the rat hippocampal neurons (i.e. the <jats:ext-link xmlns:xlink=\"http:\/\/www.w3.org\/1999\/xlink\" xlink:href=\"https:\/\/en.wikipedia.org\/wiki\/Entorhinal_cortex\">entorhinal cortex<\/jats:ext-link> from the <jats:ext-link xmlns:xlink=\"http:\/\/www.w3.org\/1999\/xlink\" xlink:href=\"https:\/\/en.wikipedia.org\/wiki\/Dentate_gyrus\">dentate gyrus<\/jats:ext-link>, the <jats:ext-link xmlns:xlink=\"http:\/\/www.w3.org\/1999\/xlink\" xlink:href=\"https:\/\/en.wikipedia.org\/wiki\/Dentate_gyrus\">dentate gyrus<\/jats:ext-link> from CA3, and CA3 from CA1) was examined by direct injection of the vector into the <jats:ext-link xmlns:xlink=\"http:\/\/www.w3.org\/1999\/xlink\" xlink:href=\"https:\/\/en.wikipedia.org\/wiki\/Dentate_gyrus\">dentate gyrus<\/jats:ext-link>, CA3 and CA1. To distinguish transduction of the neuronal and glial cells, as well as selective retrograde gene transfer, double\u2010staining of the green fluorescent protein (GFP) expressing cells with the specific neuron biomarker NeuN (neuronal nuclear protein) and the specific glia biomarker GFAP (glial fibrillary acidic protein) was performed across the network.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>The transgene was successfully introduced into the circuit. More than 80% of the neuronal and glial cells at the injection sites preserved GFP expression during the 2\u2010month period after vector injection. Importantly, GFP was expressed selectively in almost 80.0% of the presynaptic neuronal cells by retrograde axonal transport of the vector.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusions<\/jats:title><jats:p>The FUG\u2010B2\u2010based vector system can efficiently introduce the transgene into the rat hippocampal neurons both directly and indirectly through retrograde monosynaptic movement. This efficient and long\u2010lasting gene delivery might provide a tool for treating neurological disorders originating in hippocampal circuits.<\/jats:p><\/jats:sec>","DOI":"10.1002\/jgm.3046","type":"journal-article","created":{"date-parts":[[2018,8,7]],"date-time":"2018-08-07T04:54:32Z","timestamp":1533617672000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":6,"title":["Transduction efficacy and retrograde movement of a lentiviral vector pseudotyped by modified rabies glycoprotein throughout the trisynaptic circuit of the rat hippocampus"],"prefix":"10.1002","volume":"20","author":[{"given":"Mostafa","family":"Farzaneh","sequence":"first","affiliation":[{"name":"Department of Pharmacology, Science and Research Branch Islamic Azad University  Tehran Iran"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0603-2444","authenticated-orcid":false,"given":"Mohammad","family":"Sayyah","sequence":"additional","affiliation":[{"name":"Department of Physiology and Pharmacology Pasteur Institute of Iran  Tehran Iran"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Hamid Reza","family":"Eshraghi","sequence":"additional","affiliation":[{"name":"Department of Pharmacology, Science and Research Branch Islamic Azad University  Tehran Iran"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Negar","family":"Panahi","sequence":"additional","affiliation":[{"name":"Department of Pharmacology, Science and Research Branch Islamic Azad University  Tehran Iran"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Hadi Mirzapour","family":"Delavar","sequence":"additional","affiliation":[{"name":"Department of Physiology and Pharmacology Pasteur Institute of Iran  Tehran Iran"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Hamid Gholami","family":"Pourbadie","sequence":"additional","affiliation":[{"name":"Department of Physiology and Pharmacology Pasteur Institute of Iran  Tehran Iran"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"311","published-online":{"date-parts":[[2018,8,15]]},"reference":[{"key":"e_1_2_7_2_1","doi-asserted-by":"publisher","DOI":"10.1093\/hmg\/10.19.2109"},{"volume-title":"The rat nervous system","year":"1995","author":"Amaral DG","key":"e_1_2_7_3_1"},{"key":"e_1_2_7_4_1","first-page":"526","article-title":"The ever\u2010changing morphology of hippocampal granule neurons in physiology and pathology","volume":"9","author":"Llorens\u2010Mart\u00edn M","year":"2015","journal-title":"Front Neurosci"},{"key":"e_1_2_7_5_1","doi-asserted-by":"publisher","DOI":"10.1128\/JVI.72.11.8463-8471.1998"},{"key":"e_1_2_7_6_1","doi-asserted-by":"publisher","DOI":"10.1038\/nn.3752"},{"volume-title":"The rat brain 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