Abnormal Morphology and Synaptogenic Signaling in Astrocytes Following Prenatal Opioid Exposure

• Published in: Cells (Basel, Switzerland) Switzerland), 2024-05, Vol.13 (10), p.837
• Main Authors: Niebergall, Ethan B, Weekley, Daron, Mazur, Anna, Olszewski, Nathan A, DeSchepper, Kayla M, Radant, N, Vijay, Aishwarya S, Risher, W Christopher
• Format: Article
• Language: English
• Subjects: Analgesics, Opioid - adverse effects; Analgesics, Opioid - pharmacology; Animals; Astrocytes; Astrocytes - drug effects; Astrocytes - metabolism; Astrocytes - pathology; Brain; Brain research; Buprenorphine; Buprenorphine - pharmacology; Cell culture; Cells, Cultured; Central nervous system; Computer software industry; Culture media; Drug abuse; Drug dosages; Drug withdrawal; Ethylenediaminetetraacetic acid; Female; Females; International economic relations; Intrauterine exposure; Laboratory animals; Maturation; Mice; Mice, Inbred C57BL; Narcotics; Neonatal abstinence syndrome; Neural networks; Neuronal-glial interactions; Neurons; Neurons - drug effects; Neurons - metabolism; Neurons - pathology; Neurophysiology; Neurosciences; Opioid receptors; opioids; Penicillin; Pregnancy; Pregnant women; Prenatal experience; Prenatal exposure; Prenatal Exposure Delayed Effects - metabolism; Prenatal Exposure Delayed Effects - pathology; prenatal opioid exposure; Signal Transduction - drug effects; Stress response; synapses; Synapses - drug effects; Synapses - metabolism; Synaptogenesis; tripartite
• ISSN: 2073-4409; 2073-4409
• DOI: 10.3390/cells13100837

In recent decades, there has been a dramatic rise in the rates of children being born after in utero exposure to drugs of abuse, particularly opioids. Opioids have been shown to have detrimental effects on neurons and glia in the central nervous system (CNS), but the impact of prenatal opioid exposure (POE) on still-developing synaptic circuitry is largely unknown. Astrocytes exert a powerful influence on synaptic development, secreting factors to either promote or inhibit synapse formation and neuronal maturation in the developing CNS. Here, we investigated the effects of the partial µ-opioid receptor agonist buprenorphine on astrocyte synaptogenic signaling and morphological development in cortical cell culture. Acute buprenorphine treatment had no effect on the excitatory synapse number in astrocyte-free neuron cultures. In conditions where neurons shared culture media with astrocytes, buprenorphine attenuated the synaptogenic capabilities of astrocyte-secreted factors. Neurons cultured from drug-naïve mice showed no change in synapses when treated with factors secreted by astrocytes from POE mice. However, this same treatment was synaptogenic when applied to neurons from POE mice, indicating a complex neuroadaptive response in the event of impaired astrocyte signaling. In addition to promoting morphological and connectivity changes in neurons, POE exerted a strong influence on astrocyte development, disrupting their structural maturation and promoting the accumulation of lipid droplets (LDs), suggestive of a maladaptive stress response in the developing CNS.