Sugarcoated Perineuronal Nets Regulate "GABAergic" Transmission: Bittersweet Hypothesis in Autism Spectrum Disorder

Clin Neuropharmacol. May/Jun 2017;40(3):120-130. doi: 10.1097/WNF.0000000000000209.

Abstract

Fast-spiking, parvalbumin-expressing "GABAergic" interneurons regulate synchronous oscillatory output of pyramidal neurons. Metabolic demands of these GABAergic projections are great because local ion concentrations must be optimally maintained; in addition, high rates of mitochondrial respiration necessitate exquisite redox regulation. Interestingly, only fast-spiking, parvalbumin-expressing basket cells coexpressing 3 metalloproteinases seem to be preferentially enwrapped in perineuronal nets (PNNs), a specialized lattice-like structure of the extracellular matrix. The PNNs maintain optimal local concentrations of ions, protect against oxidative stress, and concentrate transcription factors and chemorepulsive axon guidance cues. The PNNs mediate opening and closing of periods of heightened plasticity. Therapeutic strategies in autism spectrum disorders include promoting both maintenance and deliberate disruption of PNNs to promote new learning and cognitive flexibility.

Publication types

  • Review

MeSH terms

  • Animals
  • Autism Spectrum Disorder / drug therapy
  • Autism Spectrum Disorder / metabolism*
  • Autism Spectrum Disorder / pathology
  • Disease Models, Animal
  • Drugs, Investigational / pharmacology
  • Drugs, Investigational / therapeutic use
  • Extracellular Matrix / drug effects
  • Extracellular Matrix / metabolism*
  • Extracellular Matrix / pathology
  • GABAergic Neurons / drug effects
  • GABAergic Neurons / metabolism*
  • GABAergic Neurons / pathology
  • Humans
  • Male
  • Models, Neurological*
  • Nerve Net / drug effects
  • Nerve Net / metabolism*
  • Nerve Net / pathology
  • Neuronal Plasticity / drug effects
  • Neuroprotection / drug effects
  • Neuroprotective Agents / pharmacology
  • Neuroprotective Agents / therapeutic use
  • Oxidative Stress / drug effects
  • Psychotropic Drugs / pharmacology
  • Psychotropic Drugs / therapeutic use
  • Pyramidal Cells / drug effects
  • Pyramidal Cells / metabolism
  • Pyramidal Cells / pathology
  • Pyramidal Tracts / drug effects
  • Pyramidal Tracts / metabolism*
  • Pyramidal Tracts / pathology
  • Synaptic Transmission* / drug effects

Substances

  • Drugs, Investigational
  • Neuroprotective Agents
  • Psychotropic Drugs