Different roles of the TrkB and p75NTR neurotrophin receptors in the Preconditioning effect in a coculture model of Status epilepticus in vitro

VICTOR DANELON; ANDREA BEATRÍZ CRAGNOLINI; LAURA MONTROULL; DANIEL MASCÒ

Congreso; 29° Reunión de la Sociedad Argentina de investigación en Neurociencias; 2014

Previous studies from our laboratory have shown that after 3 h of neuronal hyperactivation of a co-culture of hippocampal neurons and astrocytes, more than 50 % of neurons died 24 hours later. However, a short preconditioning stimulus (PS), applied 24h and not 5h, before the excitotoxic stimulus (ES), induce an almost complete neuroprotection. It is possible that modifiations in the BDNF receptors TrkB and/or p75ntr could participate in the neuroprotetion effect. To asses this question different pharmacological inhibition of the receptors was performed. Also we evaluated the possibility whether a PS modifis the proliferation rate in the astrocyte, and its modifiation by the pharmacological treatment. TrkB receptor blockade induced by the inhibitor Ana-12 totally blocked the neuroprotective effect of the PE 24 h. Similar effect was obtained when BDNF was sequestered in the culture media by TrkB fusion protein (TrkB-fc). On the other hand, the neuroprotection effect of the PC 24h was not modifid after the addition of p75ntr blocking function antibody at 24h. The PS 5h before the ES induces a signifiant increase in astrocyte proliferation only when they were cultured alone, but when co-culture in the present of neurons, only the PS 24h induces a signifiant increase in astrocyte proliferation. Taking together all these results indicate that modifiations in the endogenous relationships among BDNF receptors activation have a key role in cell death and survival determination.