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The impact of intestinal worms on the host central nervous system (CNS) remains unexplored. The aim of this study was to evaluate the effect of intestinal infection by the tapeworm <jats:italic>Hymenolepis diminuta<\/jats:italic> on behavior and functions of the CNS in rats. The 3 months old animals were infected, and the effects on anxiety, exploration, sensorimotor skills and learning processes were assessed at 18 months in Open Field (OF), Novel Object Recognition (NOR) and the Water Maze (WM) tests. After completing the behavioral studies, both infected and non-infected rats were sacrificed, and the collected tissues were subjected to biochemical analysis. The levels of neurotransmitters, their metabolites and amino acids in selected structures of the CNS were determined by HPLC. In addition, the gene expression profile of the pro- and anti-inflammatory cytokines (TNF-\u03b1, IL-1\u03b2, IL-6 and IL-10) was evaluated by Real-Time PCR to determine the immune response within the CNS to the tapeworm infection. The parasites caused significant changes in exploratory behavior, most notably, a reduction of velocity and total distance moved in the OF test; the infected rats exhibited decreased frequency in the central zone, which may indicate a higher level of anxiety. Additionally, parasite infestation improved spatial memory, assessed in the WM test, and recognition of new objects. These changes are related to the identified reduction in noradrenaline level in the CNS structures and less pronounced changes in striatal serotonergic neurotransmission. <jats:italic>H<\/jats:italic>. <jats:italic>diminuta<\/jats:italic> infestation was also found to cause a significant reduction of hippocampal expression of IL-6. Our results provide new data for further research on brain function during parasitic infections especially in relation to helminths and diseases in which noradrenergic system may play an important role.<\/jats:p>","DOI":"10.1371\/journal.ppat.1010330","type":"journal-article","created":{"date-parts":[[2022,3,14]],"date-time":"2022-03-14T17:50:41Z","timestamp":1647280241000},"page":"e1010330","update-policy":"https:\/\/doi.org\/10.1371\/journal.ppat.corrections_policy","source":"Crossref","is-referenced-by-count":19,"title":["Infection with intestinal helminth (Hymenolepis diminuta) impacts exploratory behavior and cognitive processes in rats by changing the central level of neurotransmitters"],"prefix":"10.1371","volume":"18","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-0990-3017","authenticated-orcid":true,"given":"Kamilla","family":"Blecharz-Klin","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2412-8220","authenticated-orcid":true,"given":"Magdalena","family":"\u015awierczy\u0144ska","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Agnieszka","family":"Piechal","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Adriana","family":"Wawer","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6869-4016","authenticated-orcid":true,"given":"Ilona","family":"Joniec-Maciejak","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0776-8077","authenticated-orcid":true,"given":"Justyna","family":"Pyrzanowska","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Ewa","family":"Wojnar","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6990-9165","authenticated-orcid":true,"given":"Anna","family":"Zawistowska-Deniziak","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Anna","family":"Sulima-Celi\u0144ska","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9762-9950","authenticated-orcid":true,"given":"Daniel","family":"M\u0142ocicki","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6294-3256","authenticated-orcid":true,"given":"Dagmara","family":"Mirowska-Guzel","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"340","published-online":{"date-parts":[[2022,3,14]]},"reference":[{"issue":"2","key":"ppat.1010330.ref001","doi-asserted-by":"crossref","first-page":"429","DOI":"10.1515\/ap-2016-0058","article-title":"Mass spectrometry analysis of the excretory-secretory (E-S) products of the model cestode Hymenolepis diminut a reveals their immunogenic properties and the presence of new E-S proteins in cestodes","volume":"61","author":"J Bie\u0144","year":"2016","journal-title":"Acta Parasitol"},{"key":"ppat.1010330.ref002","doi-asserted-by":"crossref","first-page":"2487","DOI":"10.3389\/fimmu.2018.02487","article-title":"Immunoproteomics and Surfaceomics of the Adult Tapeworm Hymenolepis diminuta","volume":"9","author":"D M\u0142ocicki","year":"2018","journal-title":"Front Immunol"},{"key":"ppat.1010330.ref003","doi-asserted-by":"crossref","first-page":"223","DOI":"10.1016\/S0065-308X(08)60150-5","article-title":"Immunology and biochemistry of Hymenolepis diminuta","volume":"42","author":"J Andreassen","year":"1999","journal-title":"Adv. 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