Unburned Tobacco Smoke Affects Neuroinflammation-Related Pathways in the Rat Mesolimbic System.

first_page settings Order Article Reprints Open AccessArticle Unburned Tobacco Smoke Affects Neuroinflammation-Related Pathways in the Rat Mesolimbic System by Camilla Morosini 1,† [ORCID] , Fabio Vivarelli 1,† [ORCID] , Laura Rullo 1,* [ORCID] , Emilia Volino 1,2, Loredana Maria Losapio 1 [ORCID] , Moreno Paolini 1, Patrizia Romualdi 1,* [ORCID] , Donatella Canistro 1,‡ [ORCID] and Sanzio Candeletti 1,‡ [ORCID] 1 Department of Pharmacy and Biotechnology, Alma Mater Studiorum–University of Bologna, 40126 Bologna, Italy 2 Department of Biomedical and Neuromotor Sciences, Alma Mater Studiorum–University of Bologna, 40126 Bologna, Italy * Authors to whom correspondence should be addressed. † These authors contributed equally to this work. ‡ These authors contributed equally to this work. Int. J. Mol. Sci. 2024, 25(10), 5259; https://doi.org/10.3390/ijms25105259 Submission received: 10 April 2024 / Revised: 3 May 2024 / Accepted: 9 May 2024 / Published: 11 May 2024 (This article belongs to the Collection Feature Papers in Molecular Neurobiology) Download keyboard_arrow_down Browse Figures Versions Notes Abstract Tobacco use disorder represents a significant public health challenge due to its association with various diseases. Despite awareness efforts, smoking rates remain high, partly due to ineffective cessation methods and the spread of new electronic devices. This study investigated the impact of prolonged nicotine exposure via a heat-not-burn (HnB) device on selected genes and signaling proteins involved in inflammatory processes in the rat ventral tegmental area (VTA) and nucleus accumbens (NAc), two brain regions associated with addiction to different drugs, including nicotine. The results showed a reduction in mRNA levels for PPARα and PPARγ, two nuclear receptors and anti-inflammatory transcription factors, along with the dysregulation of gene expression of the epigenetic modulator KDM6s, in both investigated brain areas. Moreover, decreased PTEN mRNA levels and higher AKT phosphorylation were detected in the VTA of HnB-exposed rats with respect to their control counterparts. Finally, significant alterations in ERK 1/2 phosphorylation were observed in both mesolimbic areas, with VTA decrease and NAc increase, respectively. Overall, the results suggest that HnB aerosol exposure disrupts intracellular pathways potentially involved in the development and maintenance of the neuroinflammatory state. Moreover, these data highlight that, similar to conventional cigarettes, HnB devices use affects specific signaling pathways shaping neuroinflammatory process in the VTA and NAc, thus triggering mechanisms that are currently considered as potentially relevant for the development of addictive behavior.