Fluorene is one of the most abundant polycyclic aromatic hydrocarbons in air and may contribute to the neurobehavioral alterations induced by the environmental exposure of humans to PAHs. Since no data are available on fluorene neurotoxicity, this study was conducted in adult rats to assess the behavioral toxicity of repeated fluorene inhalation exposure. Male rats (n = 18/group) were exposed nose-only to 1.5 or 150 ppb of fluorene 6 hours/day for 14 consecutive days, whereas the control animals were exposed to non-contaminated air. At the end of the exposure, animals were tested for activity and anxiety in an open-field and in an elevated-plus maze, for short-term memory in a Y-maze, and for spatial learning in an eight-arm maze. The results showed that the locomotor activity and the learning performances of the animals were unaffected by fluorene. In parallel, the fluorene-exposed rats showed a lower level of anxiety than controls in the open-field, but not in the elevated-plus maze, which is probably due to a possible difference in the aversive feature of the two mazes. In the same animals, increasing blood and brain levels of fluorene monohydroxylated metabolites (especially the 2-OH fluorene) were detected at both concentrations (1.5 and 150 ppb), demonstrating the exposure of the animals to the pollutant and showing the ability of this compound to be metabolized and to reach the cerebral compartment. The present study highlights the possibility for a 14-day fluorene exposure to induce some specific anxiety-related behavioral disturbances, and argues in favor of the susceptibility of the adult brain when exposed to volatile fluorene.

Airborne pollution, especially from diesel exhaust (DE), is known to have a negative effect on the central nervous system in exposed human populations. However, the consequences of gestational exposure to DE on the fetal brain remain poorly explored, with various effects depending on the conditions of exposure, as well as little information on early developmental stages. We investigated the short-term effects of indirect DE exposure throughout gestation on the developing brain using a rabbit model. We analyzed fetal olfactory tissues at the end of gestation and tested behaviors relevant to pups’ survival at birth. Pregnant dams were exposed by nose-only inhalation to either clean air or DE with a content of particles (DEP) adjusted to 1 mg/m3 by diluting engine exhaust, for 2 h/day, 5 days/week, from gestational day 3 (GD3) to day 27 (GD27). At GD28, fetal olfactory mucosa, olfactory bulbs and whole brains were collected for anatomical and neurochemical measurements. At postnatal day 2 (PND2), pups born from another group of exposed or control female were examined for their odor-guided behavior in response to the presentation of the rabbit mammary pheromone 2-methyl-3-butyn-2-ol (2MB2). At GD28, nano-sized particles were observed in cilia and cytoplasm of the olfactory sensory neurons in the olfactory mucosa and in the cytoplasm of periglomerular cells in the olfactory bulbs of exposed fetuses. Moreover, cellular and axonal hypertrophies were observed throughout olfactory tissues. Concomitantly, fetal serotoninergic and dopaminergic systems were affected in the olfactory bulbs. Moreover, the neuromodulatory homeostasis was disturbed in a sex-dependent manner in olfactory tissues. At birth, the olfactory sensitivity to 2MB2 was reduced in exposed PND2 pups. Gestational exposure to DE alters olfactory tissues and affects monoaminergic neurotransmission in fetuses’ olfactory bulbs, resulting in an alteration of olfactory-based behaviors at birth. Considering the anatomical and functional continuum between the olfactory system and other brain structures, and due to the importance of monoamine neurotransmission in the plasticity of neural circuits, such alterations could participate to disturbances in higher integrative structures, with possible long-term neurobehavioral consequences.

Recent climate change-induced wildfires and nuclear energy phasing-out policies have fostered atmospheric emissions of polycyclic aromatic hydrocarbons (PAHs). PAHs are pollutants produced by natural and anthropic processes under thermal treatment of organic matter, e.g. in fires and sedimentary rocks (Henner et al. 1997, Lichtfouse et al. 1997). They occur widely in the environment from trace levels, e.g. in polar ice, to high concentrations in oil spills. They have been found in aerosols, soils, sediments, waters, meterorites, coal, petroleum, bitumen and living organisms. Surprisingly, out of the 16 polycyclic aromatic hydrocarbons defined as 'priority' polluants for toxicity evaluation, ten light homologues have been poorly investigated because they did not show obvious carcinogenic effects. Here, we argue that the toxicity of light PAHs has been overlooked (Fig. 1).

Metabolic Dysfunction-Associated Steatotic Liver Disease (MASLD) is a chronic liver disease affecting 25% of the European population, with rising global incidence. Liver damage includes ballooning, steatosis, inflammation and fibrosis. Associated brain disorders include sleep, cognitive issues, anxiety, and depression. While neurological complications in advanced MASLD are well documented, early cerebral manifestations remain largely unexplored. This study aimed at developing an MASLD rat model to assess the onset of early brain damage, focusing on impairments of the circadian cycle rhythm and associated neuroinflammation. Sprague Dawley rats were divided into two groups: one received a high-fat, high-cholesterol (HFHC) diet for 90 days, while the other received a standard diet. Histological analysis showed significant hepatic steatosis, ballooning, and inflammation in the HFHC group (p < 0.01). These lesions correlated with elevated hepatic triglycerides (p < 0.01), increased Alanine Aminotransferase, Aspartate Aminotransferase, total cholesterol, and low-density lipoprotein, alongside decreased plasma high-density lipoprotein. Behavioural analysis using activity wheels revealed that the HFHC rats steadily maintained their activity level during the rest periods when compared with controls (p < 0.05). This behavioural alteration occurred alongside neuroinflammation, demonstrated by changes in the expression of 36 and 17 inflammatory mediators in the cerebellum and frontal cortex respectively. These changes were associated with an increase in the expression of glial cell markers (Aif1 and Gfap genes) and an increase in the number of microglial cells, affecting the frontal cortex and cerebellum differently. This rat model of early MASLD shows circadian rhythm disturbances, which could reflect sleep disorders in humans. These early brain disturbances specific to MASLD, which occur before the symptoms of liver disease become clinically apparent, could therefore be used as an early diagnosis marker for MASLD patients.