GISNe - Anatomia, Farmacologia e Medicina Legale

INVOLVEMENT OF NERVE GROWTH FACTOR (NGF) AND BRAIN-DERIVED NEUROTROPHIC
FACTOR (BDNF) IN NEUROENDOCRINE REGULATIONS AND VULNERABILITY TO STRESS IN ANIMAL
MODELS
Francesca Cirulli and Enrico Alleva
Behavioural Neurosciences Section, Department of Cell Biology and Neurosciences,
Istituto Superiore di Sanità, Rome Italy (cirulli@iss.it)
Nerve Growth Factor (NGF) and Brain-Derived Neurotrophic Factor (BDNF) are key molecular players in
brain growth and differentiation. Most importantly, numerous data indicate that neurotrophins can
orchestrate interactions between the nervous, endocrine and immune system, and are involved in important
regulations of sleep/wake cycles and of circadian secretion of hypothalamic hormones which might pave the
way to increased vulnerability to psychiatric disorders. Research conducted by our group, in collaboration
with the group led by Rita Levi-Montalcini, has clearly indicated an involvement of NGF in emotionally
arousing situations in animal models of psychosocial stress, such as male mice intraspecific fighting.
Furthermore, we have shown that, in humans, highly arousing situations, such as the uncertainty caused by
the anticipation of the first jump with a parachute by army soldiers, result in increased blood levels of NGF,
underlying the relative independence of this neurotrophin from other neuroendocrine effectors, and its
sensitivity to environmental variables having a social nature. In another series of studies we have shown that
exposure to stressful experiences in rodents can have important short- and long-term effects on neurotrophin
levels in the central nervous system, leading to an increased risk for vulnerability to stress at adulthood. In
collaboration with the NIMH (Prof. S. Suomi, Laboratory of Comparative Ethology, USA), we are currently
investigating, in a primate model, whether exposure to early life stress can have short- and long- term effects
on neuroendocrine regulations, with a special emphasis on NGF and BDNF levels assessed in the peripheral
circulation and in the cerebrospinal fluid of rhesus macaques.