Bryostatin 1 Promotes Synaptogenesis and Reduces Dendritic Spine Density in Cortical Cultures through a PKC-Dependent Mechanism

Calvin Ly, Akira J. Shimizu, Maxemiliano V. Vargas, Whitney C. Duim, Paul A. Wender, David E. Olson

Research output: Contribution to journalArticle

Abstract

The marine natural product bryostatin 1 has demonstrated procognitive and antidepressant effects in animals and has been entered into human clinical trials for treating Alzheimer's disease (AD). The ability of bryostatin 1 to enhance learning and memory has largely been attributed to its effects on the structure and function of hippocampal neurons. However, relatively little is known about how bryostatin 1 influences the morphology of cortical neurons, key cells that also support learning and memory processes and are negatively impacted in AD. Here, we use a combination of carefully designed chemical probes and pharmacological inhibitors to establish that bryostatin 1 increases cortical synaptogenesis while decreasing dendritic spine density in a protein kinase C (PKC)-dependent manner. The effects of bryostatin 1 on cortical neurons are distinct from those induced by neural plasticity-promoting psychoplastogens such as ketamine. Compounds capable of increasing synaptic density with concomitant loss of immature dendritic spines may represent a unique pharmacological strategy for enhancing memory by improving signal-to-noise ratio in the central nervous system.

Original languageEnglish (US)
JournalACS Chemical Neuroscience
DOIs
StateAccepted/In press - Jan 1 2020

Keywords

  • Alzheimer's disease
  • bryostatin 1
  • dendritic spines
  • protein kinase C
  • synaptogenesis

ASJC Scopus subject areas

  • Biochemistry
  • Physiology
  • Cognitive Neuroscience
  • Cell Biology

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