Nimodipine inhibits TMB-8 potentiation of AMPA-induced hippocampal neurodegeneration.
Human cerebral calcification has been related to deregulation of intracellular calcium homeostasis. In rat basal ganglia, nimodipine and TMB-8, two commonly used calcium antagonists, worsen the chronic AMPA-induced lesion, whereas only nimodipine potentiates calcification. To investigate whether similar effects are present in the hippocampus, AMPA dose-response and calcium movement blockade were performed. A dose-related increase of both hippocampal lesion and calcification was evident in a saturable mode, mostly different from the continuous globus pallidus response previously observed. The value of 2.7 nmol AMPA, selected as yielding 60% of maximum calcification, was coinjected with nimodipine or/and TMB-8 to determine their influence on tissue damage. TMB-8 increased the AMPA lesion in terms of calcified area, and nimodipine reversed this increase, with no effect alone. These results, divergent from those for the globus pallidus, reveal differences in extra- and intracellular calcium movement between the two neurodegenerative processes. Future work focused on other brain areas is required to understand how control of calcium stores may influence neurodegenerative disease evolution.
Bernal
Fabián
F
Unitat de Bioquímica, IDIBAPS, Facultat de Medicina, Universitat de Barcelona, Barcelona, Spain.
Petegnief
Valerie
V
Rodríguez
Manuel José
MJ
Ursu
Gloria
G
Pugliese
Marco
M
Mahy
Nicole
N
D000704:Analysis of Variance; D000818:Animals; D000880:Anthraquinones; D001345:Autoradiography; D002114:Calcinosis / Q000139:chemically induced; D002121:Calcium Channel Blockers / Q000494:pharmacology*; D004305:Dose-Response Relationship, Drug; D005707:Gallic Acid / Q000031:analogs & derivatives* / Q000494:pharmacology; D006624:Hippocampus / Q000187:drug effects* / Q000473:pathology / Q000503:physiopathology; D008297:Male; D008995:Monoamine Oxidase / Q000378:metabolism; D009474:Neurons / Q000187:drug effects* / Q000502:physiology; D009553:Nimodipine / Q000494:pharmacology*; D051381:Rats; D017207:Rats, Sprague-Dawley; D011963:Receptors, GABA-A / Q000378:metabolism; D018350:alpha-Amino-3-hydroxy-5-methyl-4-isoxazolepropionic Acid / Q000378:metabolism*
D000880:Anthraquinones; D002121:Calcium Channel Blockers; D011963:Receptors, GABA-A; C006014:8-(N,N-diethylamino)octyl-3,4,5-trimethoxybenzoate; D009553:Nimodipine; C010078:alizarin; D005707:Gallic Acid; D018350:alpha-Amino-3-hydroxy-5-methyl-4-isoxazolepropionic Acid; D008995:Monoamine Oxidase