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

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Abstract

Previously 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 both Becn1+/+ and Becn1+/- 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 in Becn1+/+ mice, but not in similarly treated Becn1+/- mice. Brain homogenates from Becn1+/+ 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 treated Becn1+/- mice. Likewise, increased neuronal loss was detected when both Tat and morphine were administered to Becn1+/+ mice, but not in similarly treated Becn1+/- mice. Overall, our findings show that there is a Beclin1-driven interaction between Tat and morphine in glia and neurons. Moreover, reduced glial-Beclin1 may provide a layer of protection to neurons under stressful conditions, such as when exposed to morphine and Tat.

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The data that support the findings of this study are available from the corresponding author upon reasonable request.

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Acknowledgements

We are grateful to Chet Raj Ojha for intellectual input. Funding for these studies were provided by the National Institutes of Health (NIH)-National Institute on Drug Abuse (NIDA) grant DA036154 awarded to NEH and grant DA036154-S1 Diversity Supplement awarded to NEH to support JL. National Institute on Mental health (NIMH) grant MH118985 awarded to NEH and National Institute of General Medical Sciences (NIGMS) T32GM132054-01 support to MP.

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  1. Department of Immunology and Nanomedicine, Florida International University, Herbert Wertheim College of Medicine, Miami, FL, 33199, USA

    Jessica Lapierre, Mohan K. M. Karuppan, Marissa Perry, Myosotys Rodriguez & Nazira El-Hage

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  1. Jessica Lapierre
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  2. Mohan K. M. Karuppan
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  3. Marissa Perry
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  5. Nazira El-Hage
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Correspondence to Nazira El-Hage.

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Lapierre, J., Karuppan, M.K.M., Perry, M. et al. Different Roles of Beclin1 in the Interaction Between Glia and Neurons after Exposure to Morphine and the HIV- Trans-Activator of Transcription (Tat) Protein. J Neuroimmune Pharmacol 17, 470–486 (2022). https://doi.org/10.1007/s11481-021-10017-4

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