PMID- 17552998
OWN - NLM
STAT- MEDLINE
DCOM- 20070815
LR  - 20210223
IS  - 0953-816X (Print)
IS  - 0953-816X (Linking)
VI  - 25
IP  - 11
DP  - 2007 Jun
TI  - Long-term reduction of brain-derived neurotrophic factor levels and signaling 
      impairment following prenatal treatment with the cannabinoid receptor 1 receptor 
      agonist (R)-(+)-[2,3-dihydro-5-methyl-3-(4-morpholinyl-methyl) 
      pyrrolo[1,2,3-de]-1,4-benzoxazin-6-yl]-1- naphthalenylmethanone.
PG  - 3305-11
AB  - It is well accepted that adverse life events occurring early in development may 
      alter the correct program of brain maturation leading to enhanced vulnerability 
      to neuropsychiatric disorders. It has recently been demonstrated that prenatal 
      exposure to the cannabinoid receptor 1 agonist 
      (R)-(+)-[2,3-dihydro-5-methyl-3-(4-morpholinyl-methyl)pyrrolo[1,2,3-de]-1,4-benzoxazin-6-yl]-1-naphthalenylmethanone 
      (WIN 55,212-2) produces memory deficit in adulthood, an effect associated with a 
      reduced functionality of the glutamatergic system. The aim of our study was to 
      identify molecular changes produced by prenatal exposure to WIN 55,212-2 that 
      might contribute to late disruption in synaptic plasticity and cognition. For 
      this purpose, WIN 55,212-2 was injected in pregnant wistar rats from gestation 
      day 5 to 20 and a detailed analysis of the levels of the neurotrophin 
      brain-derived neurotrophic factor (BDNF) as well as of the signaling molecules 
      extracellular signal-regulated kinase (ERK)1/2 and 
      alpha-calcium/calmodulin-dependent protein kinase II (alpha-CaMKII) was carried 
      out in adult offspring. We found that exposure to WIN 55,212-2 significantly 
      reduced BDNF levels in hippocampus and frontal cortex. This effect was associated 
      with decreased activation of pathways linked to neurotrophin and glutamate 
      receptor signaling. In particular, prenatal cannabinoid treatment reduced the 
      phosphorylated levels of ERK1/2 in selected subcellular compartments of 
      hippocampus, frontal and prefrontal cortex, whereas no changes were observed in 
      the total levels of these proteins. Furthermore, a robust reduction of total and 
      phospho-alpha-CaMKII was found in the hippocampus of rats prenatally exposed to 
      WIN 55,212-2. In summary, the present data suggest that deficits of BDNF levels 
      and signaling through ERK1/2 and alpha-CaMKII might contribute to cognitive and 
      neuroplastic defects associated with prenatal exposure to cannabinoids.
FAU - Maj, Paola Francesca
AU  - Maj PF
AD  - Center of Neuropharmacology, Department of Pharmacological Sciences, University 
      of Milan, Via Balzaretti 9, 20133 Milan, Italy.
FAU - Collu, Maria
AU  - Collu M
FAU - Fadda, Paola
AU  - Fadda P
FAU - Cattaneo, Annamaria
AU  - Cattaneo A
FAU - Racagni, Giorgio
AU  - Racagni G
FAU - Riva, Marco Andrea
AU  - Riva MA
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
PL  - France
TA  - Eur J Neurosci
JT  - The European journal of neuroscience
JID - 8918110
RN  - 0 (Benzoxazines)
RN  - 0 (Brain-Derived Neurotrophic Factor)
RN  - 0 (Calcium Channel Blockers)
RN  - 0 (Morpholines)
RN  - 0 (Naphthalenes)
RN  - 0 (Receptor, Cannabinoid, CB1)
RN  - 5H31GI9502 
      ((3R)-((2,3-dihydro-5-methyl-3-((4-morpholinyl)methyl)pyrrolo-(1,2,3-de)-1,4-benzoxazin-6-yl)(1-naphthalenyl))methanone)
SB  - IM
MH  - Animals
MH  - Benzoxazines/pharmacology
MH  - Brain/anatomy & histology/drug effects/metabolism
MH  - Brain-Derived Neurotrophic Factor/*metabolism
MH  - Calcium Channel Blockers/pharmacology
MH  - Female
MH  - Gene Expression Regulation/drug effects
MH  - Morpholines/pharmacology
MH  - Naphthalenes/*pharmacology
MH  - Pregnancy
MH  - *Prenatal Exposure Delayed Effects/chemically induced/metabolism/physiopathology
MH  - Rats
MH  - Rats, Wistar
MH  - Receptor, Cannabinoid, CB1/*agonists
MH  - Signal Transduction/*drug effects
EDAT- 2007/06/08 09:00
MHDA- 2007/08/19 09:00
CRDT- 2007/06/08 09:00
PHST- 2007/06/08 09:00 [pubmed]
PHST- 2007/08/19 09:00 [medline]
PHST- 2007/06/08 09:00 [entrez]
AID - EJN5565 [pii]
AID - 10.1111/j.1460-9568.2007.05565.x [doi]
PST - ppublish
SO  - Eur J Neurosci. 2007 Jun;25(11):3305-11. doi: 10.1111/j.1460-9568.2007.05565.x.