Decreased metabolic response to visual stimulation in the superior colliculus of mice lacking the glial glutamate transporter GLT‐1

Abstract

During a specific task, an increase in glucose utilization anatomically restricted to the functionally activated region(s) is a landmark of brain physiology. While this response represents the biological bases for functional brain imaging, the underlying signalling pathway(s) are still not fully characterized. Recent evidence suggests that glial glutamate (re)uptake plays a key role. We provide evidence that the metabolic response to synaptic activation (i.e. enhancement of glucose uptake) is decreased in the superior colliculus during visual stimulation in young adult mice deficient in the glial glutamate transporter GLT-1. A similar reduction was not observed in the glial glutamate transporter GLAST-knockout mice. Consistent with our previous observation obtained in the somatosensory cortex, our data suggest that a metabolic crosstalk takes place between neurons and astrocytes in the adult brain which would be regulated by synaptic activity and mediated by GLT-1.

Activation of Astrocytes by CNTF Induces Metabolic Plasticity and Increases Resistance to Metabolic Insults

“…The striatum of lenti-CNTF, lenti-LacZ, or Veh rats (n ϭ 4 -5 per group) was rapidly dissected out on ice. Tissue samples and cell cultures were homogenized, and Western blots were made as described previously (Herard et al, 2005) using the ECL detection technique (GE Healthcare, Little Chalfont, UK). Films were scanned, and optical density was measured and normalized to actin.…”

Ciliary Neurotrophic Factor Activates Astrocytes, Redistributes Their Glutamate Transporters GLAST and GLT-1 to Raft Microdomains, and Improves Glutamate HandlingIn Vivo

“…Western blots were performed using ECL detection as described previously (Herard et al, 2005). The antibodies used were raised against actin (1:10,000), ␤-III-tubulin (1:1000), calbindin D (1:1000), connexin 43 (1:250; BD Biosciences, San Jose, CA), dopamine and cAMPregulated phosphoprotein (DARPP-32; 1:1000; Chemicon, Temecula, CA), excitatory amino acid carrier 1 (EAAC1; 1:1000; Alpha Diagnostics International, San Antonio, TX), flotilin-1 (1:500; BD Biosciences), GFAP (1:2000; Dako, High Wycombe, UK), glutamic acid decarboxylase (GAD; 1:3000; Chemicon), glutamate receptor subunit 2 (GluR2; 1:500; Chemicon), nestin (1:1000; BD Biosciences), NMDA receptor subunit 2A (NR2A; 1:500; Santa Cruz Biotechnology, Santa Cruz, CA), NR2B (1:500; Santa Cruz Biotechnology), proliferating cell nuclear antigen (PCNA) (1:1000), STAT3 (1:1000; Cell Signaling Technology, Beverly, MA), phospho-STAT3 (Tyr705; 1:1000; Cell Signaling Technology), synaptophysin (1:250), vesicular glutamate transporter 1 (VGLUT1; 1:1000; a kind gift from Prof. S. El Mestikawy, Institut Mondor de Médecine Moléculaire, Créteil, France) and vimentin (1:200; Dako).…”

Differential Effects of NMDA and AMPA Glutamate Receptors on Functional Magnetic Resonance Imaging Signals and Evoked Neuronal Activity during Forepaw Stimulation of the Rat

“…This hypothesis has received in vivo experimental support from both magnetic resonance spectroscopy studies (for review, see Rothman et al, 2003) and recent findings that increases in cerebral glucose utilization after somatosensory or visual stimulation are markedly reduced in knock-out mice deficient for each of the two glial glutamate transporters GLAST and GLT-1 (Voutsinos-Porche et al, 2003a,b;Herard et al, 2005).…”