[Neuron damage in the rat spinal cord induced by acromelic acid].
A single systemic injection of acromelic acid, a novel kainate analogue, caused long-lasting spastic paraparesis in the rat. Two rats that developed paraparesis were neuropathologically examined one week and three months after the injection, respectively. Numerous degenerated neurons with marked reactive gliosis were scattered in the gray matter of the spinal cord of the rat with paraparesis for one week. Degenerated neurons were most abundant in the core part of lumbar and sacral segments. The cytometry on the 1st sacral segment disclosed that the number of small neurons was significantly decreased. No morphological sign of neuron damage was demonstrated in the rest of the central nervous system. These pathological changes were responsible for the development of characteristic behavioral changes which were quite different from those induced by kainic acid. The regional difference between the neuron damage induced by acromelic acid and that induced by kainic acid suggests the presence of plural kinds of kainate receptor subtypes in the rat central nervous system. This assumption is supported by receptor binding studies on glutamate receptor subtypes, indicating the low affinity of acromelic acid for both kainate and AMPA binding sites. Acromelic acid may exert its potent depolarizing and neurotoxic effects through activating a new class of kainate receptor subtypes.
Shin
K
K
D000818:Animals; D016923:Cell Death / Q000187:drug effects; D007608:Kainic Acid / Q000009:adverse effects / Q000031:analogs & derivatives*; D009474:Neurons / Q000187:drug effects / Q000473:pathology; D015493:Paraparesis, Tropical Spastic / Q000139:chemically induced* / Q000473:pathology; D051381:Rats; D013116:Spinal Cord / Q000187:drug effects* / Q000473:pathology
C051743:acromelic acid A; D007608:Kainic Acid