ReviewPsychiatric vulnerability: Suggestions from animal models and role of neurotrophins
Section snippets
NGF and psychiatric diseases
In the last decades, after the impulse and the mass communication explosion that followed the seminal work of the neuroscientist Rita Levi-Montalcini (awarded the Nobel Prize in 1986), the studies on the role exerted by neurotrophins (NTs) on central nervous system (CNS) and behavior have greatly increased.
In November 1986, the semi-popular magazine “New Scientist” entitled “Nerve growth factor—a potential cure-all?” in its “News and Views”, where the idea that nerve growth factor (NGF) action
The “global vulnerability”
Progressive alteration of NTs levels in blood or and/or neural tissue may be responsible for individual vulnerability to psychiatric diseases. As an example about vulnerability in general, we selected the classical case of diabetes, a disease in which physiological, weakly or heavily pathological, with intermediate (paraphysiological) levels of insulin, vary along a gradient of insulin levels in the bloodstream (see Fig. 1).
Presently, diabetes is viewed as a morbid affliction not only
BDNF also modulates brain plasticity and coping
BDNF was described first in 1982 (about 30 years later the NGF discovery), as the culmination of studies mainly performed at the Biozentrum of the University of Basel (Switzerland). Although several investigators have participated, the course of BDNF discovery has been largely charted by Yves-Alain Barde, with the unflinching support of Hans Thoenen (Barde et al., 1982).
In contrast to NGF and NT-3 transcripts, which are abundant in peripheral tissues, BDNF mRNA is predominantly synthesized in
Clinical relevance of the neurotrophins and therapeutic perspectives
Accumulating evidences from clinical, preclinical and animal studies indicate a key role for NTs in the pathophysiology of psychiatric diseases. Indeed, as already reported in this review, low plasma levels of NGF were found in schizophrenic patients (Bersani et al., 1999, Parikh et al., 2003), while low serum BDNF levels have been reported in both schizophrenic patients and patients with depressive disorders (Karege et al., 2002, Toyooka et al., 2002). A recent study performed on patients
General conclusion
NTs are key factors in mediating both short- and long-term experience effects on brain structure and function. However, much remains to be understood about the role played by NGF and BDNF on CNS targets regulating brain plasticity and behavioral coping both during development and at adulthood.
Moreover, further insight into physiological processes controlled by NTs may eventually yield innovative therapeutic tools for psychopathologies, including innovative peptidergic drugs. Indeed, data
Acknowledgments
Work supported by the ISS-NIH Collaborative Project (0F14) to EA and FC and by the Italian Ministry of Health, Ricerca Finalizzata ex art. 12 - 2006, to EA. The authors thank Giovanni Dominici and Simona Miletta for technical support, and Francesca Cirulli, Daniela Santucci, Igor Branchi, Walter Adriani and Giovanni Laviola for useful comments on the manuscript.
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