Tobacco-free cigarette smoke exposure induces anxiety and panic-related behaviours in male wistar rats.

Smokers, who generally present with lung damage, are more anxious than non-smokers and have an associated augmented risk of panic. Considering that lung damage signals specific neural pathways that are related to affective responses, the aim of the present study was to evaluate the influence of pulmonary injury on anxiety and panic-like behaviours in animals exposed to cigarette smoke with and without tobacco. Male Wistar rats were divided into the following groups: a control group (CG); a regular cigarette group (RC); and a tobacco-free cigarette (TFC) group. Animals were exposed to twelve cigarettes per day for eight consecutive days. The animals were then exposed to an elevated T-maze and an open field. The RC and TFC groups presented increases in inflammatory cell inflow, antioxidant enzyme activity, and TBARS levels, and a decrease in the GSH/GSSG ratio was observed in the TFC group. Exposure to RC smoke reduced anxiety and panic-related behaviours. On the other hand, TFC induced anxiety and panic-related behaviours. Thus, our results contradict the concept that nicotine is solely accountable for shifted behavioural patterns caused by smoking, in that exposure to TFC smoke causes anxiety and panic-related behaviours.Cigarette smoke exposure is associated with anxiety states. Smokers are more anxious than non-smokers1, while cigarette smoking cessation is associated with increased levels of anxiety and stress, as the nicotine in cigarettes has been shown to have anxiolytic effects2. Moreover, smoking is also associated with an augmented risk of panic attacks, and quitting smoking could help reduce this risk3. Importantly, in a study conducted by Amaring and colleagues, it was reported that 72% of panic disorder patients declared that they were regular smokers at the onset of their disease4. Cigarette smoke is also one of the several agents and environmental factors that can trigger oxidative stress and pulmonary damage5. Cigarette smoke causes cellular recruitment, lipid peroxidation, production of inflammatory mediators, and oxidative stress6?11. For instance, studies in mice have shown that exposure to short-term cigarette smoke evokes an increase in inflammatory cell inflow and oxidative damage6,9. In general, exposure to pollutants induces pulmonary inflammation through the generation of oxidative stress12,13, defined as the imbalance in reactive oxygen species production, to the detriment of the antioxidant defence systems14. Importantly, exposure to ambient air particles not only induces pulmonary inflammation but also behavioural disorders both in humans and in mice15. Currently, the majority of anxiety studies associated with cigarette smoking have focused on the anxiolytic effects of nicotine2. However, it has been shown that lung damage can induce central nervous system responses by activating specific neuronal pathways16,17, which include those linked to affective responses, such as anxiety and panic18. This raises the question of whether the anxiety and panic-type behaviour associated with smoking might be related not only to the nicotine or to tobacco?s other constituents but also to lung damage

Influ?ncia da inflama??o pulmonar sobre comportamento em ratos wistar expostos ? fuma?a de cigarro.

Programa de P?s-Gradua??o em Ci?ncias Biol?gicas. N?cleo de Pesquisas em Ci?ncias Biol?gicas, Pr?-Reitoria de Pesquisa de P?s Gradua??o, Universidade Federal de Ouro Preto.A fuma?a de cigarro (FC) ? uma combina??o complexa, que cont?m mais de 7.000 subst?ncias qu?micas, as quais podem promover dano oxidativo no par?nquima pulmonar e processo inflamat?rio. ? importante ressaltar que a inflama??o pulmonar leva a ativa??o de neur?nios no sistema nervoso central. Entretanto, os mecanismos neurais impl?citos e a rela??o da inflama??o pulmonar com o comportamento do tipo p?nico e ansiedade n?o ? ainda claro. O objetivo do presente estudo foi avaliar a influ?ncia da inflama??o pulmonar no comportamento de ansiedade de animais expostos ? fuma?a do cigarro com e sem tabaco. Vinte e quatro ratos Wistar machos (protocolo n? 2015/35) foram divididos em tr?s grupos: grupo controle (GC); cigarro comum (CC) e cigarro de papel (CP), sem tabaco (por conseguinte, sem nicotina). Os animais foram expostos a doze cigarros por dia em tr?s per?odos (manh?, tarde e noite), durante oito dias consecutivos. Al?m da exposi??o ? FC, os animais foram submetidos a testes comportamentais: Labirinto em T elevado e Campo aberto. Os animais foram eutanasiados para retirada do lavado broncoalveolar (LBA), do sangue e pulm?o. O LBA foi usado para contagem total, diferencial de c?lulas e para a dosagem de citocinas pr?-inflamat?rias; o plasma sangu?neo foi analisado para dosagem de citocinas; e o pulm?o foi usado para dosagem das Prote?nas totais, sistema Glutationa, enzimas antioxidantes: SOD e CAT, TBARS e prote?na carbonilada. A exposi??o ? fuma?a do CC reduziu os comportamentos do tipo ansiedade e p?nico. Por outro lado, o CP induziu comportamento do tipo ansiedade e p?nico. Os animais expostos a FC comum e de papel apresentaram um aumento do influxo de c?lulas inflamat?rias (CC: 170 ? 3,162 x 103/ml e CP: 180 ? 6,547 x 103/ml vs. CG: 118 ? 6,665 x 103/ml); aumento da atividade das enzimas antioxidantes: SOD (CC: 34,86 ? 1,855 U/mg prot e CP: 40,65 ? 3,444 U/mg prot vs. CG: 25,73 ? 1,092 U/mg prot) e CAT (CC: 0.96 ? 0.06 U/mg prot e CP: 0.94 ? 0.10 U/mg prot vs. CG: 0.68 ? 0.10 U/mg prot). A exposi??o tamb?m gerou dano pulmonar como demonstrado pelo aumento dos n?veis de TBARS (CC: 1.39 ? 0.15 nM/mg prot e CP: 1.54 ? 0.10 nM/mg prot vs. GC: 1.02 ? 0.05 nM/mg prot) e redu??o da raz?o GSH/GSSG (CC: 4,016 ? 0,5503 ?M e CP: 3,316 ? 0,8901 ?M vs. GC: 7,283 ? 0,6019, ?M). Al?m da an?lise estereologica dos cortes de pulm?o, que evidenciaram altera??o da histoarquitetura por meio do aumento do volume do espa?o alveolar (CC: 57,46 ? 1,92 %/mm? e CP: 53,40 ? 1,83 %/mm? vs. GC: 43,36 ? 3,46 %/mm?) e redu??o do volume do septo alveolar (CC: 41,60 ? 1,95 %/mm? e CP: 46,21 ? 1,85%/mm? vs. GC: 55,28 ? 3,52 %/mm?) nos animais expostos. A exposi??o ? fuma?a do cigarro comum bem como a do cigarro de papel (sem tabaco) conduziu igualmente a processo inflamat?rio e dano pulmonar, que pode promover altera??o de comportamento do tipo p?nico e ansiedade.Cigarette smoke (CF) is a complex combination that contains more than 7,000 chemicals, which can promote oxidative damage to the lung parenchyma and inflammatory process. It is important to emphasize that pulmonary inflammation leads to the activation of neurons in the central nervous system. However, the neural mechanisms implicit and the relationship between lung inflammation and panic and anxiety behavior are not clear. The aim of the present study was to evaluate the influence of pulmonary inflammation on anxiety behavior of animals exposed to cigarette smoke with and without tobacco. Twenty-four male Wistar rats (protocol n. 2015/35) were divided into three groups: control group (CG); Common cigarette (CC) and paper cigarette (CP), without tobacco (therefore without nicotine). The animals were exposed to twelve cigarettes per day in three periods (morning, afternoon and night) for eight consecutive days. In addition to CF exposure, the animals were submitted to behavioral tests: Elevated T-maze and open field. The animals were euthanized for removal of bronchoalveolar lavage (BAL), blood and lung. LBA was used for total count, cell differential and for the measurement of pro-inflammatory cytokines; Blood plasma was analyzed for cytokine dosing; And the lung was used for dosage of the total Proteins, Glutathione system, antioxidant enzymes: SOD and CAT, TBARS and carbonylated protein. Exposure to CC smoke reduced anxiety and panick-like behaviors. On the other hand, CP induced panic and anxiety behaviors. Animals exposed to common and paper CF showed an increase in influx of inflammatory cells (CC: 170 ? 3.162 x 103/ml and CP: 180 ? 6.547 x 103/ml vs. CG: 118 ? 6.665 x 103/ml); increased activity of antioxidant enzymes: SOD (CC: 34.86 ? 1.855 U/mg prot and CP: 40.65 ? 3.444 U/mg prot vs. CG: 25.73 ? 1.092 U/mg prot) and CAT (CC : 0.96 ? 0.06 U/mg prot and CP: 0.94 ? 0.10 U/mg prot vs. CG: 0.68 ? 0.10 U/mg prot). The exposure also generated lung damage as demonstrated by increased TBARS levels (CC: 1.39 ? 0.15 nM/mg prot and CP: 1.54 ? 0.10 nM/mg prot vs. GC: 1.02 ? 0.05 nM/mg prot) and reduction of the ratio GSH/GSSG (CC: 4.016 ? 0.5503 ?M and CP: 3.316 ? 0.8901 ?M vs. GC: 7.283 ? 0.6019 ?M). In addition to the stereological analysis of the lung sections, which also showed alteration of histoarchitecture by increasing the volume of the alveolar space (CC: 57.46 ? 1.92%/mm? and CP: 53.40 ? 1.83%/mm? Vs. GC: 43.36 ? 3.46%/mm?) and alveolar septal volume reduction (CC: 41.60 ? 1.95%/mm? and CP: 46.21 ? 1.85%/mm? vs. GC: 55.28 ? 3.52%/mm?) in the exposed animals. Exposure to common cigarette smoke as well as paper cigarettes (without tobacco) led to an inflammatory process and lung damage, problably leadind to a change in panic and anxiety behaviors

High-Fat diet increases HMGB1 expression and promotes lung inflammation in mice subjected to mechanical ventilation.

This study aims to evaluate the effects of a high-fat diet and mechanical ventilation on the pulmonary and systemic inflammatory response in C57BL/6 mice. Male C57BL/6 mice were divided into two groups: one received a standard diet, and the other received a high-fat diet. After 10 weeks, the groups were further divided into two groups each: control group (CG), mechanical ventilation group (MVG), diet group (DG), and diet mechanical ventilation group (DMVG). MVG and DMVG underwent mechanical ventilation for 60 minutes. All animals were euthanized for subsequent analysis. Animals receiving a high-fat diet presented higher body mass, adipose index, and greater adipocyte area. In the lung, the expression of HMGB1 was greater in DG and DMVG than in CG and MVG. CCL2 and IL-22 levels in MVG and DMVG were increased compared to those in CG and DG, whereas IL-10 and IL-17 were decreased. Superoxide dismutase activity was higher in MVG and DMVG than in CG. Catalase activity was lower in DG than in CG, and in MV groups, it was lower than that in CG and DG. MV and obesity promote inflammation and pulmonary oxidative stress in adult C57BL/6 mice

Association of high-fat diet with neuroinflammation, anxiety-like defensive behavioral responses, and altered thermoregulatory responses in male rats.

Overweight and obesity are a worldwide pandemic affecting billions of people. These conditions have been associated with a chronic low-grade inflammatory state that is recognized as a risk factor for a range of somatic diseases as well as neurodevelopmental disorders, anxiety disorders, trauma- and stressor-related disorders, and affective disorders. We previously reported that the ingestion of a high-fat diet (HFD; 45% fat kcal/g) for nine weeks was capable of inducing obesity in rats in association with increased reactivity to stress and increased anxiety-related defensive behavior. In this study, we conducted a nine-week diet protocol to induce obesity in rats, followed by investigation of anxiety-related defensive behavioral responses using the elevated T-maze (ETM), numbers of FOS-immunoreactive cells after exposure of rats to the avoidance or escape task of the ETM, and neuroinflammatory cytokine expression in hypothalamic and amygdaloid nuclei. In addition, we investigated stress-induced cutaneous thermoregulatory responses during exposure to an open-field (OF). Here we demonstrated that nine weeks of HFD intake induced obesity, in association with increased abdominal fat pad weight, increased anxiety-related defensive behavioral responses, and increased proinflammatory cytokines in hypothalamic and amygdaloid nuclei. In addition, HFD exposure altered avoidance- or escape task-induced FOSimmunoreactivity within brain structures involved in control of neuroendocrine, autonomic, and behavioral responses to aversive stimuli, including the basolateral amygdala (BLA) and dorsomedial (DMH), paraventricular (PVN) and ventromedial (VMH) hypothalamic nuclei. Furthermore, rats exposed to HFD, relative to control dietfed rats, responded with increased tail skin temperature at baseline and throughout exposure to an open-field apparatus. These data are consistent with the hypothesis that HFD induces neuroinflammation, alters excitability of brain nuclei controlling neuroendocrine, autonomic, and behavioral responses to stressful stimuli, and enhances stress reactivity and anxiety-like defensive behavioral responses