Spinal cord mGlu1a receptors: possible target for amyotrophic lateral sclerosis therapy.
Amyotrophic lateral sclerosis (ALS) is a neurodegenerative disorder characterized by the progressive loss of motor neurons, whose pathogenesis, probably multifactorial, is thought to involve AMPA/kainate receptor-mediated Ca2+ influx and excitotoxicity. We evaluated the possible involvement of Group I metabotropic glutamate (mGlu) receptors in the control of motor neuron viability. mGlu1a receptor distribution was analyzed in rat and human spinal cord by immunohistochemistry. In both species, the expression of mGlu1a receptor was developmentally regulated and showed a general trend to increase during foetal and postnatal maturation, reaching the maximum level of expression in the dorsal laminae I-II and in motor neurons in adult life. Exposure of spinal cord slices from adult rats to 300 microM kainate for 30 min induced motor neuron death, which was prevented by the Group I mGlu receptor agonist 3-hydroxyphenylglycine (3-HPG; 100 microM). Since motor neurons do not express mGlu5 receptors, mGlu1a receptor activation might be responsible for the observed neuroprotection. mGlu1a immunohistochemistry was conducted on spinal cord autoptic specimens from ALS and control subjects. Surviving motor neurons from ALS spinal cord still revealed the presence of mGlu1a at levels comparable to that from controls. We suggest that mGlu1a receptors may act as suitable targets for ALS experimental therapies.
Division of Pharmacology, Department of Biomedical Sciences and Biotechnologies, Brescia University School of Medicine,Via Valsabbina 19, Brescia, Italy.
Alessandra
A
Valerio
Marina
M
Ferrario
Marta
M
Paterlini
Paolo
P
Liberini
Giuseppe
G
Moretto
Nigel J
NJ
Cairns
Marina
M
Pizzi
PierFranco
P
Spano
D000690:Amyotrophic Lateral Sclerosis / Q000188:drug therapy* / Q000473:pathology; D000818:Animals; D002470:Cell Survival / Q000187:drug effects; D018690:Excitatory Amino Acid Agonists / Q000494:pharmacology; D018691:Excitatory Amino Acid Antagonists / Q000494:pharmacology; D005260:Female; D005727:Ganglia, Spinal / Q000187:drug effects / Q000378:metabolism; D005998:Glycine / Q000031:analogs & derivatives* / Q000494:pharmacology; D006801:Humans; D007150:Immunohistochemistry; D007608:Kainic Acid / Q000494:pharmacology; D009046:Motor Neurons / Q000187:drug effects / Q000473:pathology; D009410:Nerve Degeneration / Q000139:chemically induced / Q000473:pathology; D011247:Pregnancy; D051381:Rats; D017207:Rats, Sprague-Dawley; D018094:Receptors, Metabotropic Glutamate / Q000819:agonists / Q000037:antagonists & inhibitors / Q000187:drug effects*; D013116:Spinal Cord / Q000187:drug effects / Q000196:embryology / Q000378:metabolism*
D018690:Excitatory Amino Acid Agonists; D018691:Excitatory Amino Acid Antagonists; D018094:Receptors, Metabotropic Glutamate; C104077:metabotropic glutamate receptor type 1; C023010:4-hydroxyphenylglycine; D007608:Kainic Acid; D005998:Glycine