Developmental exposure to polycyclic aromatic hydrocarbons (PAHs): Focus on benzo[a]pyrene neurotoxicity.

Polycyclic Aromatic Hydrocarbons (PAHs) are a class of ubiquitous organic compounds produced during the incomplete combustion or pyrolysis of organic material. Dietary source is the main route for PAH human exposure by environmental contamination, food industrial processing or domestic cooking methods. The most studied PAH is benzo[a]pyrene (B[a]P), due to its harmful and multiple effects on human health: in addition to its well-known carcinogenic effects, emerging evidence indicates that B[a]P also induces neurotoxicity earlier and at lower doses than B[a]P-induced carcinogenicity making B[a]P neurotoxicity relevant to human health risk assessment. Developmental neurotoxicity of B[a]P has indeed received increasing attention: both human and experimental studies provide evidence of detrimental effects of prenatal or early postnatal B[a]P exposure, even at low doses. Indeed, in some of the multi-dose animal studies, maximal adverse effects were observed at lower B[a]P doses, according to a non-monotonic dose-response curve typical of endocrine-disrupting compounds. In substantial agreement with epidemiological studies, both rodents and zebrafish developmentally exposed to B[a]P exhibit long-term changes in multiple behavioural domains, in the absence of overt toxicological effects at birth (e.g. body weight and morphologic abnormalities). Notably, most targeted behavioural responses converge on locomotor activity and emotional profile, often, but not always, leading to a disinhibitory/hyperactive profile.

When Nerve Growth Factor Met Behavior.

Since its first characterization in the early 1950s, the role of the polypeptidic nerve growth factor (NGF) in controlling behavior remained elusive. Since the mid-1980s, we undertook a series of experiments aimed at elucidating the biological role(s) played by neurotrophins, particularly NGF, in adult rodents. At the beginning, we concentrated on the submandibular salivary gland of the male mouse, which was known to store massive amount of NGF. We found that under specific stress conditions, the salivary NGF is released in the bloodstream: intermale fighting between isolated males was the first reported context in which salivary NGF was released, thus providing a physiological significance for its presence in the adult, territorial males. We also found that dominant males release less NGF than subordinates and provided a loop-type model which includes intermale social confrontation, adrenal gland size, and functional status, corticosterone release, a model resulting in likelihood to be stabilized in a "dominant" or a "subordinate" social status. A variety of social anxiety contexts of mammals, humans included, has been described since then, and further studies carried out on humans showed that NGF is released in the bloodstream of parachutists at their first skydiving experience and in the case of ranking high on the Passionate Love Scale (amour fou). Ethological data from lab rodents helped in understanding NGF function in subtly controlling social "status" of male mice: the considerations about the interplay among neurobiological, physiological, and behavioral factors in structuring the dominant vs subordinate phenotypes may well apply to other vertebrate species, specifically addressing the underlying role of neurotrophins in relating behavior and brain neuroplasticity.