+ Site Statistics
+ Search Articles
+ PDF Full Text Service
How our service works
Request PDF Full Text
+ Follow Us
Follow on Facebook
Follow on Twitter
Follow on LinkedIn
+ Subscribe to Site Feeds
Most Shared
PDF Full Text
+ Translate
+ Recently Requested

Neuronal activity and glutamate uptake decrease mitochondrial mobility in astrocytes and position mitochondria near glutamate transporters

Neuronal activity and glutamate uptake decrease mitochondrial mobility in astrocytes and position mitochondria near glutamate transporters

Journal of Neuroscience 34(5): 1613-1624

Within neurons, mitochondria are nonuniformly distributed and are retained at sites of high activity and metabolic demand. Glutamate transport and the concomitant activation of the Na(+)/K(+)-ATPase represent a substantial energetic demand on astrocytes. We hypothesized that mitochondrial mobility within astrocytic processes might be regulated by neuronal activity and glutamate transport. We imaged organotypic hippocampal slice cultures of rat, in which astrocytes maintain their highly branched morphologies and express glutamate transporters. Using time-lapse confocal microscopy, the mobility of mitochondria within individual astrocytic processes and neuronal dendrites was tracked. Within neurons, a greater percentage of mitochondria were mobile than in astrocytes. Furthermore, they moved faster and farther than in astrocytes. Inhibiting neuronal activity with tetrodotoxin (TTX) increased the percentage of mobile mitochondria in astrocytes. Mitochondrial movement in astrocytes was inhibited by vinblastine and cytochalasin D, demonstrating that this mobility depends on both the microtubule and actin cytoskeletons. Inhibition of glutamate transport tripled the percentage of mobile mitochondria in astrocytes. Conversely, application of the transporter substrate d-aspartate reversed the TTX-induced increase in the percentage of mobile mitochondria. Inhibition of reversed Na(+)/Ca(2+) exchange also increased the percentage of mitochondria that were mobile. Last, we demonstrated that neuronal activity increases the probability that mitochondria appose GLT-1 particles within astrocyte processes, without changing the proximity of GLT-1 particles to VGLUT1. These results imply that neuronal activity and the resulting clearance of glutamate by astrocytes regulate the movement of astrocytic mitochondria and suggest a mechanism by which glutamate transporters might retain mitochondria at sites of glutamate uptake.

Please choose payment method:

(PDF emailed within 0-6 h: $19.90)

Accession: 054586448

Download citation: RISBibTeXText

PMID: 24478345

DOI: 10.1523/jneurosci.3510-13.2014

Related references

Neuronal influences are necessary to produce mitochondrial co-localization with glutamate transporters in astrocytes. Journal of Neurochemistry 130(5): 668-677, 2014

Dual regulation of Ca2+-dependent glutamate release from astrocytes: vesicular glutamate transporters and cytosolic glutamate levels. Glia 57(12): 1296-1305, 2009

Riluzole and gabapentinoids activate glutamate transporters to facilitate glutamate-induced glutamate release from cultured astrocytes. European Journal of Pharmacology 677(1-3): 87-92, 2012

The GLT-1 and GLAST glutamate transporters are expressed on morphologically distinct astrocytes and regulated by neuronal activity in primary hippocampal cocultures. Journal of Neurochemistry 75(3): 1076-1084, 2000

Glucose replaces glutamate as energy substrate to fuel glutamate uptake in glutamate dehydrogenase-deficient astrocytes. Journal of Neuroscience Research 93(7): 1093-1100, 2015

GFA Content, Glutamate Uptake and Activity of Glutamate Metabolizing Enzymes in Differentiating Mouse Astrocytes in Primary Cultures. Developmental Neuroscience 1(5): 226-238, 1978

Characterization of glutamate transporters and determination of their uptake activity in primary cultures of neuronal cells. Fundamental & Clinical Pharmacology 14(3): 282, May-June, 2000

Glutamate uptake into astrocytes stimulates aerobic glycolysis: a mechanism coupling neuronal activity to glucose utilization. Proceedings of the National Academy of Sciences of the United States of America 91(22): 10625-9, 1994

Developmental expression of glutamate transporters and glutamate dehydrogenase in astrocytes of the postnatal rat hippocampus. Hippocampus 14(8): 975-985, 2004

Involvement of glutamate transporters in glutamate-induced suppression of stellation in cultured rat cortical astrocytes. Journal of Pharmacological Sciences 94(Suppl. 1): 180P, 2004

High extracellular glutamate modulates expression of glutamate transporters and glutamine synthetase in cultured astrocytes. Brain Research 1297: 1-8, 2009

Decrease in glutamate uptake following treatment of astrocytes with MPTP. Society for Neuroscience Abstracts 22(1-3): 2130, 1996

Compromised glutamate transport in human glioma cells: reduction-mislocalization of sodium-dependent glutamate transporters and enhanced activity of cystine-glutamate exchange. Journal of Neuroscience 19(24): 10767-10777, 1999

Cysteine uptake by the neuronal subtype of glutamate transporters in cortical neuronal cultures. Society for Neuroscience Abstracts 27(2): 1873, 2001

Toward a new role for plasma membrane sodium-dependent glutamate transporters of astrocytes: maintenance of antioxidant defenses beyond extracellular glutamate clearance. Amino Acids 42(1): 181-197, 2012