Title:Prolactin Protects Against the Methamphetamine-Induced Cerebral Vascular Toxicity
Volume: 10
Issue: 4
Author(s): Hector Rosas-Hernandez, Elvis Cuevas, Susan M. Lantz-MPeak, Syed F. Ali and Carmen Gonzalez
Affiliation:
Keywords:
Blood-brain barrier, brain endothelial cells, methamphetamine, prolactin, tight junctions, trans-endothelial
electrical resistance.
Abstract: Methamphetamine (Meth) is a highly addictive drug of abuse which alters the dopaminergic system and
damages the blood-brain barrier (BBB), structure that protects the brain tissue from the circulating substances in the
blood, keeping a low permeability through the presence of tight junctions (TJs) between endothelial cells. Meth increases
BBB permeability by decreasing the TJs proteins claudin-5 and occludin and by decreasing the viability of endothelial
cells. Individuals abused of Meth have increased blood concentrations of prolactin (PRL); hormone related with milk
production, but able to increase the expression of TJs proteins and to decrease permeability on the mammary epithelium
and brain endothelial cells. However, the effects of PRL on the permeability of the BBB in the presence of Meth have not
been studied. Here, we report Meth-induced apoptosis and decreased cellular proliferation as well as the trans-endothelial
electrical resistance (TEER), related to a decrease of claudin-5 and occludin in primary cultured bovine brain microvessel
endothelial cells. The expression of the PRL receptor was not altered. Administration of PRL prevented a decrease in
cellular proliferation, an increase in apoptosis and restored the TEER and TJs proteins to basal levels. This protection was
absent at high Meth concentrations. These data suggest that PRL protects brain endothelial cells against the Meth-induced
toxicity. Further investigation is required to study the mechanisms involved and to confirm these effects in vivo.
