Different Roles of Beclin1 in the Interaction Between Glia and Neurons after Exposure to Morphine and the HIV- Trans-Activator of Transcription (Tat) Protein

AbstractPreviously we showed that Beclin1 has a regulatory role in the secretion of inflammatory molecules in glia after exposure to morphine and Tat (an HIV protein). Here we show increased secretion of neuronal growth factors and increased neuronal survival in Beclin1-deficient glia. However, without glia co-culture, neurons deficient in Beclin1 showed greater death and enhanced dendritic beading when compared to wild-type neurons, suggesting that glial-secreted growth factors compensate for the damage reduced autophagy causes neurons. To assess if our ex vivo results correlated with in vivo studies, we used a wild-type (Becn1+/+) and Beclin1-deficient (Becn1+/+) mouse model and intracranially infused the mice with Tat and subcutaneously administered morphine pellets. After morphine implantation, significantly impaired locomotor activities were detected in bothBecn1+/+ andBecn1+/- mice, irrespective of Tat infusion. After induction of pain, morphine-induced antinociception was detected. Interestingly, co-exposure to morphine and Tat increased sensitivity to pain inBecn1+/+ mice, but not in similarly treatedBecn1+/- mice. Brain homogenates fromBecn1+/+ mice exposed to Tat, alone and in combination with morphine, showed increased secretion of pro-inflammatory cytokines and reduced expression of growth factors when compared to similarly treatedBecn1+/- mice. Likewise, increased neuronal loss was detected when both Tat and morphine were administered toBecn1+/+ mice, but not in...

Source: Journal of NeuroImmune Pharmacology - November 5, 2021 Category: Drugs & Pharmacology Source Type: research