Type

Journal Article

Authors

Jochen H M Prehn
Heinrich J Huber
Ujval Anilkumar
Heiko Düssmann
Niamh M C Connolly

Subjects

Biochemistry

Topics
glycine animals glucose membrane potential mitochondrial cells cultured mice single cell analysis cerebral cortex energy metabolism neurotoxins metabolism cytology drug effects glutamic acid optical imaging genetics anoxia toxicity neurons deoxyglucose pharmacokinetics deficiency calcium animals newborn rats physiology pharmacology cerebellum luminescent proteins

Single-cell imaging of bioenergetic responses to neuronal excitotoxicity and oxygen and glucose deprivation. (2014)

Abstract Excitotoxicity is a condition occurring during cerebral ischemia, seizures, and chronic neurodegeneration. It is characterized by overactivation of glutamate receptors, leading to excessive Ca(2+)/Na(+) influx into neurons, energetic stress, and subsequent neuronal injury. We and others have previously investigated neuronal populations to study how bioenergetic parameters determine neuronal injury; however, such experiments are often confounded by population-based heterogeneity and the contribution of effects of non-neuronal cells. Hence, we here characterized bioenergetics during transient excitotoxicity in rat and mouse primary neurons at the single-cell level using fluorescent sensors for intracellular glucose, ATP, and activation of the energy sensor AMP-activated protein kinase (AMPK). We identified ATP depletion and recovery to energetic homeostasis, along with AMPK activation, as surprisingly rapid and plastic responses in two excitotoxic injury paradigms. We observed rapid recovery of neuronal ATP levels also in the absence of extracellular glucose, or when glycolytic ATP production was inhibited, but found mitochondria to be critical for fast and complete energetic recovery. Using an injury model of oxygen and glucose deprivation, we identified a similarly rapid bioenergetics response, yet with incomplete ATP recovery and decreased AMPK activity. Interestingly, excitotoxicity also induced an accumulation of intracellular glucose, providing an additional source of energy during and after excitotoxicity-induced energy depletion. We identified this to originate from extracellular, AMPK-dependent glucose uptake and from intracellular glucose mobilization. Surprisingly, cells recovering their elevated glucose levels faster to baseline survived longer, indicating that the plasticity of neurons to adapt to bioenergetic challenges is a key indicator of neuronal viability.
Collections Ireland -> Royal College of Surgeons in Ireland -> PubMed

Full list of authors on original publication

Jochen H M Prehn, Heinrich J Huber, Ujval Anilkumar, Heiko Düssmann, Niamh M C Connolly

Experts in our system

1
Jochen H M Prehn
Royal College of Surgeons in Ireland
Total Publications: 206
 
2
Heinrich J Huber
Royal College of Surgeons in Ireland
Total Publications: 39
 
3
Ujval Anilkumar
Royal College of Surgeons in Ireland
Total Publications: 14
 
4
Heiko Düssmann
Royal College of Surgeons in Ireland
Total Publications: 45
 
5
Niamh M C Connolly
Royal College of Surgeons in Ireland
Total Publications: 14