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Anesthetics Exposure in Synaptogenesis Linked to Cognitive Dysfunction in Adulthood

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— 1 min read

Scientists have discovered that exposure to anesthetics during the process of synaptogenesis can lead to apoptosis and subsequent cognitive dysfunction in adulthood. Research conducted in the United States found that anesthetics can suppress tissue plasminogen activator (tPA) release from neurons, enhancing p75 neurotrophic receptor (p75(NTR)) signaling and reducing synapses, resulting in apoptosis.

Key Takeaways:

  • Exposure to anesthetics during synaptogenesis can induce apoptosis and cognitive dysfunction in adulthood.
  • Probrain-derived neurotrophic factor (proBDNF) is involved in synaptogenesis and can induce neuronal apoptosis via p75(NTR).
  • The anesthetic isoflurane decreased tPA release, reduced drebrin expression (marker of dendritic filopodial spines), and enhanced cleaved caspase-3 (Cl-Csp3) in neurons.
  • Tissue plasminogen activator (tPA), plasmin, or p75(NTR) inhibition blocked isoflurane-mediated reduction in dendritic filopodial spines and neuronal apoptosis in vitro.
  • In vivo, isoflurane reduced synapses and enhanced Cl-Csp3 in the hippocampus of postnatal day 5-7 (PND5-7) mice, which was mitigated by p75(NTR) inhibition.
  • Researchers concluded that the hypothesis that anesthetics suppress tPA release, enhance proBDNF/p75(NTR)-mediated apoptosis, and result in cognitive dysfunction is supported.
  • The study's findings were published in Anesthesiology (Inhibition of p75 Neurotrophin Receptor Attenuates Isoflurane-mediated Neuronal Apoptosis in the Neonatal Central Nervous System. Anesthesiology, 2009;110(4)):813-825).

Statistics:

  • Researchers exposed primary neurons in vitro (DIV5) and postnatal day 5-7 (PND5-7) mice to isoflurane at 0.4% for 4 hours.
  • Electron microscopy was used to assess changes in synapses in PND5-7 mouse hippocampi.
  • Intraperitoneal injection of TAT-Pcp5 was administered to PND5-7 mice 15 minutes before isoflurane exposure.
  • The study found a reduction in dendritic filopodial spines and an increase in Cl-Csp3 in neurons exposed to isoflurane.
  • TPA, plasmin, or p75(NTR) inhibition blocked isoflurane-mediated reduction in dendritic filopodial spines and neuronal apoptosis in vitro.

Sources:

  • B.P. Head et al., "Inhibition of p75 Neurotrophin Receptor Attenuates Isoflurane-mediated Neuronal Apoptosis in the Neonatal Central Nervous System." Anesthesiology, vol. 110, no. 4, 2009, pp. 813-825.
  • P.M. Patel, University of California, 3350 La Jolla Village Dr., San Diego, CA 92161, USA.
  • Lippincott Williams & Wilkins, 530 Walnut St., Philadelphia, PA 19106-3621, USA.

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