{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,1,27]],"date-time":"2026-01-27T23:52:42Z","timestamp":1769557962632,"version":"3.49.0"},"reference-count":75,"publisher":"PAGEPress Publications","issue":"s1","license":[{"start":{"date-parts":[[2021,11,23]],"date-time":"2021-11-23T00:00:00Z","timestamp":1637625600000},"content-version":"unspecified","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc\/4.0"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Eur J Histochem"],"abstract":"<jats:p>Evidence suggests that transient receptor potential (TRP) ion channels dysfunction significantly contributes to the physiopathology of metabolic and neurological disorders. Dysregulation in functions and expression in\u00a0genes encoding the TRP channels cause several inherited diseases in humans (the so-called \u2018TRP channelopathies\u2019), which affect the cardiovascular, renal, skeletal, and nervous systems. This study aimed to evaluate\u00a0the expression of ion channels in the forebrain of rats with diet-induced obesity (DIO). DIO rats were studied after 17 weeks under a hypercaloric diet (high-fat diet, HFD) and were compared to the control rats with a\u00a0standard diet (CHOW). To determine the systemic effects of HFD exposure, we examined food intake, fat mass content, fasting glycemia, insulin levels, cholesterol, and triglycerides. qRT-PCR, Western blot, and immunochemistry analysis were performed in the frontal cortex (FC) and hippocampus (HIP). After 17 weeks of HFD,\u00a0DIO rats increased their body weight significantly compared to the CHOW rats. In DIO rats, TRPC1 and TRPC6 were upregulated in the HIP, while they were downregulated in the FC. In the case of TRPM2 expression,\u00a0instead was increased both in the HIP and in the FC. These could be related to the increase of proteins and nucleic acid oxidation. TRPV1 and TRPV2 gene expression showed no differences both in the FC and HIP. In\u00a0general, qRT-PCR analyses were confirmed by Western blot analysis. Immunohistochemical procedures highlighted\u00a0the expression of the channels in the cell body of neurons and axons, particularly for the TRPC1 and\u00a0TRPC6. The alterations of TRP channel expression could be related to the activation of glial cells or the neurodegenerative process presented in the brain of the DIO rat highlighted with post synaptic protein (PSD 95)\u00a0alterations. The availability of suitable animal models may be useful for studying possible pharmacological treatments to counter obesity-induced brain injury. The identified changes in DIO rats may represent the first insight to characterize the neuronal alterations occurring in obesity. Further investigations are necessary to characterize\u00a0the role of TRP channels in the regulation of synaptic plasticity and obesity-related cognitive decline.<\/jats:p>","DOI":"10.4081\/ejh.2021.3305","type":"journal-article","created":{"date-parts":[[2021,11,24]],"date-time":"2021-11-24T07:51:56Z","timestamp":1637740316000},"source":"Crossref","is-referenced-by-count":12,"title":["Ion channels alterations in the forebrain of high-fat diet fed rats"],"prefix":"10.4081","volume":"65","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-6482-6117","authenticated-orcid":false,"given":"Proshanta","family":"Roy","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7702-7784","authenticated-orcid":false,"given":"Ilenia","family":"Martinelli","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Michele","family":"Moruzzi","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Federica","family":"Maggi","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8711-9941","authenticated-orcid":false,"given":"Consuelo","family":"Amantini","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8044-1206","authenticated-orcid":false,"given":"Maria Vittoria","family":"Micioni Di Bonaventura","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6180-828X","authenticated-orcid":false,"given":"Carlo","family":"Cifani","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Francesco","family":"Amenta","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7219-6917","authenticated-orcid":false,"given":"Seyed Khosrow","family":"Tayebati","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9062-3305","authenticated-orcid":false,"given":"Daniele","family":"Tomassoni","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"2549","published-online":{"date-parts":[[2021,11,23]]},"reference":[{"key":"4769","doi-asserted-by":"crossref","unstructured":"Belsky DW, Caspi A, Goldman-Mellor S, Meier MH, Ramrakha S, Poulton R, et al. 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Principles of selective ion transport in channels and pumps. Science 2005;310:1461-5.","DOI":"10.1126\/science.1113666"},{"key":"4774","doi-asserted-by":"crossref","unstructured":"Gees M, Colsoul B, Nilius B. The role of transient receptor potential cation channels in Ca2+ Signaling. Cold Spring Harb Perspect Biol 2010;2:a003962.","DOI":"10.1101\/cshperspect.a003962"},{"key":"4775","doi-asserted-by":"crossref","unstructured":"Gualdani R, Gailly P. How TRPC channels modulate hippocampal function. Int J Mol Sci 2020;21:3915.","DOI":"10.3390\/ijms21113915"},{"key":"4776","doi-asserted-by":"crossref","unstructured":"Ciardo MG, Ferrer-Montiel A. Lipids as central modulators of sensory TRP channels. Biochim Biophys Acta Biomembr 2017;1859:1615-8.","DOI":"10.1016\/j.bbamem.2017.04.012"},{"key":"4777","doi-asserted-by":"crossref","unstructured":"Schaefer M. Homo- and heteromeric assembly of TRP channel subunits. 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TRPC1 mediated the increase in store-operated Ca2+entry is required for the proliferation of adult hippocampal neuronal progenitor cells. Cell Calcium 2012;51:486-96.","DOI":"10.1016\/j.ceca.2012.04.014"},{"key":"4792","doi-asserted-by":"crossref","unstructured":"Riccio A, Medhurst AD, Mattei C, Kelsell RE, Calver AR, Randall AD, et al. mRNA distribution analysis of human TRPC family in CNS and peripheral tissues. Brain Res Mol Brain Res 2002;109:95-104.","DOI":"10.1016\/S0169-328X(02)00527-2"},{"key":"4793","doi-asserted-by":"crossref","unstructured":"Jia Y, Zhou J, Tai Y, Wang Y. TRPC channels promote cerebellar granule neuron survival. Nat Neurosci 2007;10:559-67.","DOI":"10.1038\/nn1870"},{"key":"4794","doi-asserted-by":"crossref","unstructured":"Zhou J, Du W, Zhou K, Tai Y, Yao H, Jia Y, et al. Critical role of TRPC6 channels in the formation of excitatory synapses. 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TRPM2 channel in microglia as a new player in neuroinflammation associated with a spectrum of central nervous system pathologies. Front Pharmacol 2019;10:239.","DOI":"10.3389\/fphar.2019.00239"},{"key":"4799","doi-asserted-by":"crossref","unstructured":"Bond CE, Greenfield SA. Multiple cascade effects of oxidative stress on astroglia. Glia 2007;55:1348-61.","DOI":"10.1002\/glia.20547"},{"key":"4800","doi-asserted-by":"crossref","unstructured":"Liu M, Huang W, Wu D, Priestley J V. TRPV1, but not P2X, requires cholesterol for its function and membrane expression in rat nociceptors. Eur J Neurosci 2006;24:1-6.","DOI":"10.1111\/j.1460-9568.2006.04889.x"},{"key":"4801","doi-asserted-by":"crossref","unstructured":"Zsombok A, Derbenev AV. TRP Channels as therapeutic targets in diabetes and obesity. 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Increased TRPC5 glutathionylation contributes to striatal neuron loss in Huntington's disease. Brain 2015;138:3030-47.","DOI":"10.1093\/brain\/awv188"},{"key":"4823","doi-asserted-by":"crossref","unstructured":"Bollimuntha S, Ebadi M, Singh BB. TRPC1 protects human SH-SY5Y cells against salsolinol-induced cytotoxicity by inhibiting apoptosis. Brain Res 2006;1099:141-9.","DOI":"10.1016\/j.brainres.2006.04.104"},{"key":"4824","doi-asserted-by":"crossref","unstructured":"Selvaraj S, Sun Y, Watt JA, Wang S, Lei S, Birnbaumer L, et al. Neurotoxin-induced ER stress in mouse dopaminergic neurons involves downregulation of TRPC1 and inhibition of AKT\/mTOR signaling. J Clin Invest 2012;122:1354-67.","DOI":"10.1172\/JCI61332"},{"key":"4825","doi-asserted-by":"crossref","unstructured":"Weimer RM, Jorgensen EM. Controversies in synaptic vesicle exocytosis. 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Homocysteine and cytosolic GSH depletion induce apoptosis and oxidative toxicity through cytosolic calcium overload in the hippocampus of aged mice: involvement of TRPM2 and TRPV1 channels. Neuroscience 2015;284:225-33.","DOI":"10.1016\/j.neuroscience.2014.09.078"},{"key":"4830","doi-asserted-by":"crossref","unstructured":"Ostapchenko VG, Chen M, Guzman MS, Xie YF, Lavine N, Fan J, et al. The transient receptor potential melastatin 2 (TRPM2) channel contributes to \u03b2-amyloid oligomer-related neurotoxicity and memory impairment. J Neurosci 2015;35:15157-69.","DOI":"10.1523\/JNEUROSCI.4081-14.2015"},{"key":"4831","doi-asserted-by":"crossref","unstructured":"Malko P, Syed Mortadza SA, McWilliam J, Jiang LH. TRPM2 channel in microglia as a new player in neuroinflammation associated with a spectrum of central nervous system pathologies. 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