EFFECTS OF PRENATAL EXPOSURE TO THE CANNABINOID AGONIST WIN 55,212-2 ON GROWTH-ASSOCIATED PROTEIN-43 EXPRESSION IN RAT HIPPOCAMPUS

SAEZ TMM,; GUADAGNOLI T,; ARONNE MP,; CALTANA L.; BRUSCO HA.

Buzios, Brasil

Congreso; I Congress IBRO/LARC of Neurosciences of Latin America, Caribbean y Iberian Peninsula. XXIII Congress of the Sociedad Argentina de Investigación en Neurociencias (SAN).; 2008

IBRO/LARC of Neurosciences of Latin America, Caribbean y Iberian Peninsula.

There is growing evidence that endocannabinoid system plays a modulatory role in specific processes of brain development such as cell proliferation, migration, neuritic elongation and guidance and synaptogenesis. The aim of this study was to assess the effects of prenatal exposures to cannabinoid CB1/CB2 receptor agonist WIN55,212-2 (WIN) on the expression of growth-associated protein 43 (GAP43), a marker of growth cones and axons, on hippocampus. GAP43 plays important roles in synaptogenesis, axonal path finding as well as regulation of cytoskeletal organization in the nerve ending. Pregnant Wistar rats were treated, from gestational day 5 to 20, at a daily WIN dose (0.75mg/kg) which causes no evident signs of toxicity or teratogenesis. Control rats (C) were injected with vehicle (0.3%Tween80/saline). One pup per litter was decapitated at postnatal day 1 (P1) and it´s brain was fixed by immersion in 4% paraformaldehyde in PBS for 4 hs. Frozen brains were sliced in a cryostast and expression of GAP43 analyzed by immunohistochemistry. The body weight of dams, length of pregnancy, litter size at birth and body weight at P1 were monitored in order to evaluate possible effects of WIN exposure on reproduction and postnatal development. Prenatal exposure to WIN did not influence dam weight gain from days 0 to 20 of pregnancy (M ±SEM; C=45.7±3.3; WIN=37.9±1.5%), pregnancy length (C=21.3±0.3; WIN=22±0 days), litter size at birth (C=13.7±1.8; WIN=11.7±0.9) and body weight at P1 (C=6.7±0.6; WIN=6.9±0.2g). Exposure to WIN significantly reduced the expression of GAP43 inthe stratum radiatum (SR) of de CA3 region (C= 35.1±1.7; WIN= 24.9±0.8%Optical Density; p<0,05).No significant changes were observed in GAP43 staining at the stratum pyramidale (SP) and stratum oriens (SO) of the CA3 or SR, SP and SO of the CA1 region. Since prenatal exposure to WIN resulted in a significant reduction of GAP43 in the CA3 SR, there might be some deleterious synaptic changes in the rat hippocampus. This work suggests that reduction of GAP43 expression might contribute to cognitive and neuroplastic defects associated with prenatal exposure to cannabinoids, previously reported.