Early maternal deprivation reduces the expression of BDNF and NMDA receptor subunits in rat hippocampus.
It is well accepted that events that interfere with the normal program of neuronal differentiation and brain maturation may be relevant for the etiology of psychiatric disorders, setting the stage for synaptic disorganization that becomes functional later in life. In order to investigate molecular determinants for these events, we examined the modulation of the neurotrophin brain-derived neurotrophic factor (BDNF) and the glutamate NMDA receptor following 24 h maternal separation (MD) on postnatal day 9. We found that in adulthood the expression of BDNF as well as of NR-2A and NR-2B, two NMDA receptor forming subunits, were significantly reduced in the hippocampus of MD rats whereas, among other structures, a slight reduction of NR-2A and 2B was detected only in prefrontal cortex. These changes were not observed acutely, nor in pre-weaning animals. Furthermore we found that in MD rats the modulation of hippocampal BDNF in response to an acute stress was altered, indicating a persistent functional impairment in its regulation, which may subserve a specific role for coping with challenging situations. We propose that adverse events taking place during brain maturation can modulate the expression of molecular players of cellular plasticity within selected brain regions, thus contributing to permanent alterations in brain function, which might ultimately lead to an increased vulnerability for psychiatric diseases.
Center of Neuropharmacology, Department of Pharmacological Sciences and Center of Excellence for Neurodegenerative Disorders, University of Milan, Milan, Italy.
M
M
Roceri
W
W
Hendriks
G
G
Racagni
B A
BA
Ellenbroek
M A
MA
Riva
D000818:Animals; D019208:Brain-Derived Neurotrophic Factor / Q000235:genetics*; D005260:Female; D005786:Gene Expression Regulation / Q000502:physiology*; D006624:Hippocampus / Q000502:physiology*; D008297:Male; D008426:Maternal Deprivation; D021122:Protein Subunits / Q000235:genetics; D015347:RNA Probes; D051381:Rats; D017208:Rats, Wistar; D016194:Receptors, N-Methyl-D-Aspartate / Q000235:genetics*; D012016:Reference Values
D019208:Brain-Derived Neurotrophic Factor; C120997:NR2A NMDA receptor; C121001:NR2B NMDA receptor; D021122:Protein Subunits; D015347:RNA Probes; D016194:Receptors, N-Methyl-D-Aspartate