GLIAL EVIDENCES OF A NEUROPROTECTIVE ROLE OF BUSPIRONE IN PRENATAL ETHANOL EXPOSURE.

EVRARD, SG; DUHALDE VEGA, M; RAMOS, AJ; TAGLIAFERRO,AP; BRUSCO, A

Magdeburg, Alemania

Simposio; Neuroprotection and neurorepair 3rd International Symposium; 2003

Prenatal ethanol exposure (PEE) is the cause of fetal alcohol syndrome and one of the leading causes of teratogenic mental retardation. Serotoninergic system as well as astrocytes are impaired by PEE. In response to the stimulation of its 5-HT1A receptors, these cells release the S-100b protein, an astroglial neurotrophic factor. S-100b have many developmental and neuroplastic actions. PEE also affects the glial fibrillary acidic protein (GFAP) expression, the main cytoskeletal astrocitic protein. The aim of this work was to study in postnatal rat offspring the possible neuroprotective action of a prenatal treatment with buspirone, a 5-HT1A agonist. Astrocytes’ GFAP and intracellular S-100b were evaluated. Female Wistar rats were exposed to ethanol 6.6% (v/v) in drinking water ad libitum for 6 weeks before breeding and during gestation; control groups received water. Rats were pair-fed with standard food. After mating pregnant females were divided into four treatment groups: CS (control-saline), CB (control-buspirone), ES (ethanol-saline) and EB (ethanol-buspirone). Between E13 and E20 each group were injected a daily subcutaneous dose (4.5 mg/kg) of buspirone or an equivalent volume of saline. Ethanol was discontinued the day of delivery. On P35 and P60, offsprings were deeply anaesthetized and perfused; their brains were processed by immunocytochemistry using antibodies directed to GFAP or S-100b. Cell area of GFAP+ astrocytes and relative optical density (ROD) of S-100b+ astrocytes in the stratum radiatum of CA1 area of the hippocampus were measured by computer-assisted image analysis and were statistically processed. In our experiments, at P35, astroglial cell area were increased evidencing the hypertrophy of reactive astrocytes only in ES group but not in CS, CB and EB. These results were also observed in P60. Accordingly, the ROD of S-100b+ cells were increased in ES group but not in CS, CB and EB both at P35 and P60. Our results showed the reduction to normal levels of the astrocitic cell area and the intracellular relative content of S-100b when buspirone was prenatally administered to PEE rats. We postulate that buspirone may have a neuroprotective role. These results further support the importance of the central role of the 5-HT1A receptors in some neuroprotective and neuroplastic phenomena.