Mitochondria controlled by UCP2 determine hypoxia-induced synaptic remodeling in the cortex and hippocampus

Neurobiol Dis. 2016 Jun:90:68-74. doi: 10.1016/j.nbd.2016.01.004. Epub 2016 Jan 9.

Abstract

We have established that mitochondrial dynamics, under metabolic control, play crucial roles in the regulation of systemic metabolism by hypothalamic circuits. The role of mitochondrial dynamics in neurons in higher brain regions is, however, ill-defined. Here we show that early postnatal exposure of animals to temporal hypoxia followed by normoxia, a major metabolic challenge on brain cells, resulted in adaptive responses of neuronal mitochondria. The number and oxygen consumption of mitochondria in cortical and hippocampal neurons were altered, while mitochondria-endoplasmic reticulum (ER) interactions were preserved. These changes coincided with increased synaptic input of neurons in the cortex and hippocampus. We identified that the changing oxygen tension triggered mitochondrial uncoupling protein 2 (UCP2) expression and showed that UCP2 is crucial for these adaptive mitochondrial responses. In UCP2 KO mice, changing oxygen tension did not induce changes in mitochondrial parameters and function but decreased mitochondria-ER contacts and resulted in loss of synapses both in the cortex and hippocampus. These observations establish that mitochondrial location controlled by UCP2 is relevant for adaptive responses of neurons in cortical and hippocampal neurons and are relevant to perinatal hypoxia-triggered circuit adaptations.

Keywords: Cortex; Hippocampus; Mitochondria; Perinatal hypoxia; Synaptic plasticity; UCP2.

MeSH terms

  • Animals
  • Cell Count
  • Cerebral Cortex / growth & development
  • Cerebral Cortex / metabolism*
  • Cerebral Cortex / pathology
  • Hippocampus / growth & development
  • Hippocampus / metabolism*
  • Hippocampus / pathology
  • Hypoxia, Brain / metabolism*
  • Hypoxia, Brain / pathology
  • Mice, Inbred C57BL
  • Mice, Knockout
  • Microscopy, Electron
  • Mitochondria / metabolism*
  • Mitochondria / pathology
  • Neuronal Plasticity / physiology
  • Neurons / metabolism
  • Neurons / pathology
  • Organ Size
  • Synapses / metabolism*
  • Synapses / pathology
  • Uncoupling Protein 2 / genetics
  • Uncoupling Protein 2 / metabolism*

Substances

  • Ucp2 protein, mouse
  • Uncoupling Protein 2