Graphene Oxide Flakes Tune Excitatory Neurotransmission in Vivo by Targeting Hippocampal Synapses

Nano Lett. 2019 May 8;19(5):2858-2870. doi: 10.1021/acs.nanolett.8b04903. Epub 2019 Apr 18.

Abstract

Synapses compute and transmit information to connect neural circuits and are at the basis of brain operations. Alterations in their function contribute to a vast range of neuropsychiatric and neurodegenerative disorders and synapse-based therapeutic intervention, such as selective inhibition of synaptic transmission, may significantly help against serious pathologies. Graphene is a two-dimensional nanomaterial largely exploited in multiple domains of science and technology, including biomedical applications. In hippocampal neurons in culture, small graphene oxide nanosheets (s-GO) selectively depress glutamatergic activity without altering cell viability. Glutamate is the main excitatory neurotransmitter in the central nervous system and growing evidence suggests its involvement in neuropsychiatric disorders. Here we demonstrate that s-GO directly targets the release of presynaptic vesicle. We propose that s-GO flakes reduce the availability of transmitter, via promoting its fast release and subsequent depletion, leading to a decline ofglutamatergic neurotransmission. We injected s-GO in the hippocampus in vivo, and 48 h after surgery ex vivo patch-clamp recordings from brain slices show a significant reduction in glutamatergic synaptic activity in respect to saline injections.

Keywords: Graphene; glutamate; hippocampal network; quantum dots; synapses.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Animals, Newborn
  • Excitatory Amino Acid Agents / chemical synthesis
  • Excitatory Amino Acid Agents / chemistry
  • Excitatory Amino Acid Agents / pharmacology
  • Glutamic Acid / metabolism
  • Graphite / chemical synthesis
  • Graphite / chemistry
  • Graphite / pharmacology*
  • Hippocampus / drug effects
  • Hippocampus / metabolism
  • Humans
  • Nanostructures / chemistry*
  • Nanostructures / therapeutic use
  • Neurodegenerative Diseases / drug therapy*
  • Neurodegenerative Diseases / physiopathology
  • Neurons / drug effects*
  • Neurons / metabolism
  • Primary Cell Culture
  • Quantum Dots / chemistry
  • Rats
  • Rats, Wistar
  • Synapses / drug effects
  • Synapses / metabolism
  • Synaptic Transmission / drug effects

Substances

  • Excitatory Amino Acid Agents
  • graphene oxide
  • Glutamic Acid
  • Graphite