BACKGROUND: Adverse life events occurring early in development may alter the correct program of brain maturation and render the organism more vulnerable to psychiatric disorders. Identification of persistent changes associated with these events is crucial for the development of novel therapeutic strategies. METHODS: We used postnatal repeated maternal deprivation (MD) from postnatal day (PND) 2-14 to investigate changes in brain-derived neurotrophic factor (BDNF) levels. RNase protection assay and enzyme linked immunosorbent assay were employed to determine the anatomic profile of neurotrophin expression at different ages following MD. RESULTS: We found that MD produces a short-term up-regulation of neurotrophin expression in hippocampus and prefrontal cortex, as measured on PND 17, whereas at adulthood, a selective reduction of BDNF expression was observed in prefrontal cortex. When adult animals were challenged with a chronic swim stress paradigm, both a reduced expression of BDNF in prefrontal cortex and a significant reduction in striatal protein levels were found only in control subjects, whereas levels in the MD group were not further decreased. CONCLUSIONS: Our data suggest that MD produces a significant reduction of BDNF expression within prefrontal cortex and striatum, which may render these structures less plastic and more vulnerable under challenging conditions.
BACKGROUND: Adverse life events occurring early in development may alter the correct program of brain maturation and render the organism more vulnerable to psychiatric disorders. Identification of persistent changes associated with these events is crucial for the development of novel therapeutic strategies. METHODS: We used postnatal repeated maternal deprivation (MD) from postnatal day (PND) 2-14 to investigate changes in brain-derived neurotrophic factor (BDNF) levels. RNase protection assay and enzyme linked immunosorbent assay were employed to determine the anatomic profile of neurotrophin expression at different ages following MD. RESULTS: We found that MD produces a short-term up-regulation of neurotrophin expression in hippocampus and prefrontal cortex, as measured on PND 17, whereas at adulthood, a selective reduction of BDNF expression was observed in prefrontal cortex. When adult animals were challenged with a chronic swim stress paradigm, both a reduced expression of BDNF in prefrontal cortex and a significant reduction in striatal protein levels were found only in control subjects, whereas levels in the MD group were not further decreased. CONCLUSIONS: Our data suggest that MD produces a significant reduction of BDNF expression within prefrontal cortex and striatum, which may render these structures less plastic and more vulnerable under challenging conditions.
Authors: Francesca Cirulli; Andreas Reif; Sabine Herterich; K Peter Lesch; Alessandra Berry; Nadia Francia; Luigi Aloe; Christina S Barr; Stephen J Suomi; Enrico Alleva Journal: Psychoneuroendocrinology Date: 2010-12-09 Impact factor: 4.905
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