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Enrico Alleva "The role of Nerve Growth Factor (NGF) in stress and coping of rodents and humans: a few perspectives to unravel the biological bases of depression"

Abstract :

Since its first characterization (early fifties), NGF was considered a powerful protein molecule exerting trophic, tropic and differentiative effects on neurons. Rather surprisingly, until the end of the seventies its action on CNS neurons was not fully demonstrated. Since 1983, in strict collaboration with Rita Levi-Montalcini and Luigi Aloe, we explored NGF role(s) on behaviour, starting with a series of studies aimed at characterizing NGF effects on mouse social stress (intermale aggressive behaviour). Biologically (ethologically) meaningful effects on adrenals and dynamic changes in selected hypothalamic areas, suggestive of renewed PNS and CNS plasticity upon social stress, were found, with a marked difference between dominant vs subordinate social role in mice. Today, NGF and its "sister neurotrophic protein" BDNF (Brain-Derived NF) are regarded as proteic factors controlling both normal and pathological behaviours, particularly mood disorders.

More recently, we investigated in laboratory rodents the effects of physical and/or social enrichment during the neonatal-to- adolescent phase, showing that adult NGF levels are markedly affected by early experiences: NGF levels increased up to 5-fold in brain areas (e.g., hippocampus, hypothalamus, striatum) and changed according to the a more divergent dominant vs subordinate roles of enriched male mice. When reviewing the phenomenon of psychatric "vulnerability " we embedded the role of NTs in a wider theoretical framework, aimed at understanding interindividual variability in terms of epigenetic interaction in which life events (in particular, early social experiences) may play a key role in the personal weakness to mood disorders, particularly depression.
In the last years, as a result of an increasingly intense production of data exploiting animal models of behavioural disturbances, the role of NGF in controlling human behaviour witnessed findings such as NGF increase upon caring for an Alzheimer spouse, quitting a smoking habit, falling in"romantic" love, overall supporting the view that NGF is an important "proteic translator" mediating between socially-arousing states (both in rodents and in humans) and plastic neuronal changes in both PNS and CNS.
Our more recent line of research regarded epigenetic effects caused by different rearing environments (critical developmental periods for CNS maturation) and their long-term repercussions on NGF and BDNF levels in the adult CNS. We found that Communal Nesting (CN) in mice, consisting in a single nest where three mothers keep their pups together and share care-giving behaviour from birth to weaning (mimicking the natural ecological niche of the mouse species) somehow shapes constitutive NT levels. At adulthood, mice reared under CN display higher propensity to interact socially and better social skills when compared to mice reared under standard laboratory rearing conditions. Furthermore, mice reared by CN show higher NGF and BDNF levels in selected brain areas, including hippocampus and hypothalamus. The possibility to exploit NTs for an innovative therapetic stratey to control anxiety and mood disorders will be discussed.

Selected publications

Levi-Montalcini R., Aloe L., and Alleva E. - "A role for nerve growth factor in nervous, endocrine and immune systems". Progress in NeuroEndocrinImmunology 3: 1-10 (1990).

Branchi I., D'Andrea I., Fiore M., Di Fausto V., Aloe L., and Alleva E. - "Early Social Enrichment Shapes Social Behavior and Nerve Growth Factor and Brain-Derived Neurotrophic Factor Levels in the Adult Mouse Brain". Biological Psychiatry 60: 690-696 (2006).

Alleva E., and Branchi I. - "NGF: A social molecule". Psychoneuroendocrinology 31: 295-296 (2006).