TY - JOUR
T1 - Release of [3H]d-aspartate induced by K+-stimulation is increased in the cervical spinal cord of the wobbler mouse
T2 - a model of motor neuron disease
AU - Bonanno, Giambattista
AU - Fumagalli, Elena
AU - Milanese, Marco
AU - Zappettini, Simona
AU - Mennini, Tiziana
PY - 2009/9
Y1 - 2009/9
N2 - The Ca2+-dependent exocytotic release of [3H]d-aspartate and [3H]GABA evoked by 15 mM KCl depolarization was studied in wobbler mice, an animal model of selective motor neuron degeneration in the cervical tract of the spinal cord. Neurotransmitters release was studied in superfusion using synaptosomes purified from the cervical or lumbar tract of the spinal cord. The early symptomatic stage (4 weeks) and the late symptomatic stage (12 weeks) of the disease were considered. Results showed that the KCl-induced release of [3H]d-aspartate was significantly increased in synaptosomes of the cervical region in wobbler mice with respect to healthy control mice, while the basal outflow was unchanged; this alteration was present both at 4 and 12 weeks. On the contrary, the KCl-induced release of [3H]d-aspartate from the lumbar spinal cord did not differ in wobbler and control mice. The KCl-induced release of [3H]GABA from cervical and lumbar spinal cord synaptosomes was unmodified at 4 weeks of age while it was moderately but significantly reduced in wobbler mice at 12 weeks, selectively in the cervical spinal cord. No changes in Km and Vmax for [3H]l-glutamate uptake were found in spinal cord synaptosomes from wobbler mice, compared to controls, both at 4 and 12 weeks of age. Taken together our data indicate the presence of an increased glutamate release in the affected region of spinal cord in wobbler mice, suggesting a possible involvement of altered glutamate homeostasis already in early stages of the wobbler disease, in the absence of appreciable changes in the uptake process.
AB - The Ca2+-dependent exocytotic release of [3H]d-aspartate and [3H]GABA evoked by 15 mM KCl depolarization was studied in wobbler mice, an animal model of selective motor neuron degeneration in the cervical tract of the spinal cord. Neurotransmitters release was studied in superfusion using synaptosomes purified from the cervical or lumbar tract of the spinal cord. The early symptomatic stage (4 weeks) and the late symptomatic stage (12 weeks) of the disease were considered. Results showed that the KCl-induced release of [3H]d-aspartate was significantly increased in synaptosomes of the cervical region in wobbler mice with respect to healthy control mice, while the basal outflow was unchanged; this alteration was present both at 4 and 12 weeks. On the contrary, the KCl-induced release of [3H]d-aspartate from the lumbar spinal cord did not differ in wobbler and control mice. The KCl-induced release of [3H]GABA from cervical and lumbar spinal cord synaptosomes was unmodified at 4 weeks of age while it was moderately but significantly reduced in wobbler mice at 12 weeks, selectively in the cervical spinal cord. No changes in Km and Vmax for [3H]l-glutamate uptake were found in spinal cord synaptosomes from wobbler mice, compared to controls, both at 4 and 12 weeks of age. Taken together our data indicate the presence of an increased glutamate release in the affected region of spinal cord in wobbler mice, suggesting a possible involvement of altered glutamate homeostasis already in early stages of the wobbler disease, in the absence of appreciable changes in the uptake process.
KW - Amyotrophic lateral sclerosis
KW - Excitotoxicity
KW - GABA release
KW - Glutamate release
KW - Glutamate uptake
KW - Wobbler mouse
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U2 - 10.1016/j.neuint.2009.03.013
DO - 10.1016/j.neuint.2009.03.013
M3 - Article
C2 - 19576518
AN - SCOPUS:67649360000
VL - 55
SP - 302
EP - 306
JO - Neurochemistry International
JF - Neurochemistry International
SN - 0197-0186
IS - 5
ER -