Premium
The VPAC 2 agonist peptide histidine isoleucine (PHI) up‐regulates glutamate transport in the corpus callosum of a rat model of amyotrophic lateral sclerosis (hSOD1 G93A ) by inhibiting caspase‐3 mediated inactivation of GLT‐1a
Author(s) -
Goursaud Stéphanie,
Focant Marylène C.,
Berger Julie V.,
Nizet Yannick,
Maloteaux JeanMarie,
Hermans Emmanuel
Publication year - 2011
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fj.11-182337
Subject(s) - glutamate receptor , agonist , medicine , biology , vasoactive intestinal peptide , endocrinology , chemistry , receptor , neuropeptide
Degeneration of corpus callosum appears in patients with amyotrophic lateral sclerosis (ALS) before clinical signs of upper motor neuron death. Considering the ALS‐associated impairment of astrocytic glutamate uptake, we have characterized the expression and activity of the glutamate transporter isoforms GLT‐1a and GLT‐1b in the corpus callosum of transgenic rats expressing a mutated form of the human superoxide dismutase 1 (hSOD1 G93A ). We have also studied the effect of peptide histidine isoleucine (PHI), a vasoactive intestinal peptide (VIP)/pituitary adenylate cyclase‐activating polypeptide (PACAP) receptor 2 (VPAC 2 ) agonist on glutamate transporters both in vivo and in callosal astrocytes. Before the onset of motor symptoms, the expression of both transporter isoforms was correlated with a constitutive activity of caspase‐3. This enzyme participates in the down‐regulation of GLT‐1 in ALS, and here we demonstrated its involvement in the selective degradation of GLT‐1a in the white matter. A single stereotactic injection of PHI into the corpus callosum of symptomatic rats decreased caspase‐3 activity and promoted GLT‐1a expression and uptake activity. Together, with evidence for a reduced expression of prepro‐VIP/PHI mRNA in the corpus callosum of transgenic animals, these data shed light on the modulatory role of the VIP/PHI system on the glutamatergic transmission in ALS.—Goursaud, S., Focant, M. C., Berger, J. V., Nizet, Y., Maloteaux, J.‐M., Hermans, E. The VPAC 2 agonist peptide histidine isoleucine (PHI) up‐regulates glutamate transport in the corpus callosum of a rat model of amyotrophic lateral sclerosis (hSOD1 G93A ) by inhibiting caspase‐3 mediated inactivation of GLT‐1a. FASEB J. 25, 3674–3686 (2011). www.fasebj.org