Guanidinoacetate administration increases acetylcholinesterase activity in striatum of rats and impairs retention of an inhibitory avoidance task.
Guanidinoacetate methyltransferase deficiency (GAMT-deficiency) is an inborn error of metabolism biochemically characterized by accumulation of guanidinoacetate (GAA) and depletion of creatine; the pathogenesis of brain dysfunction in this disorder is not yet established. In the present study we investigated the effect of intrastriatal administration of GAA on acetylcholinesterase (AChE) activity and on memory acquisition, consolidation and retrieval of step-down inhibitory avoidance task in rat. Results showed that GAA significantly increased AChE activity in rat striatum 30 min (50%) and 3 h (25%), but not 6 h after drug administration. GAA impaired test session performance when applied 30 min before training or after training, and before testing sessions, i.e., impaired memory acquisition, consolidation and retrieval. When injected with a 6 hour interval, GAA affected only memory retrieval. Although the mechanisms of action of GAA on AChE activity and on memory are unclear, these findings suggest that the accumulation of GAA found in patients with GAMT-deficiency may be one of the mechanisms involved in neural dysfunction. Further studies are necessary to evaluate these mechanisms.
Zugno
Alexandra I
AI
Departamento de Bioquímica, ICBS, Universidade Federal do Rio Grande do Sul, Rua Ramiro Barcelos, 2600-Anexo, CEP 90035-003, Porto Alegre, RS, Brazil.
Pereira
Lenir O
LO
Mattos
Cristiane
C
Scherer
Emilene B S
EB
Netto
Carlos A
CA
Wyse
Angela T S
AT
D000109:Acetylcholine / Q000378:metabolism; D000110:Acetylcholinesterase / Q000187:drug effects / Q000378:metabolism*; D000818:Animals; D001362:Avoidance Learning / Q000187:drug effects / Q000502:physiology; D020739:Brain Diseases, Metabolic, Inborn / Q000139:chemically induced / Q000201:enzymology* / Q000503:physiopathology; D003342:Corpus Striatum / Q000187:drug effects / Q000201:enzymology* / Q000503:physiopathology; D004195:Disease Models, Animal; D004789:Enzyme Activation / Q000187:drug effects / Q000502:physiology; D005998:Glycine / Q000031:analogs & derivatives / Q000378:metabolism / Q000633:toxicity; D007859:Learning Disabilities / Q000139:chemically induced / Q000201:enzymology* / Q000503:physiopathology; D009474:Neurons / Q000187:drug effects / Q000201:enzymology*; D051381:Rats; D012153:Retention, Psychology / Q000187:drug effects / Q000502:physiology; D013997:Time Factors; D015854:Up-Regulation / Q000187:drug effects / Q000502:physiology
D000110:Acetylcholinesterase; C004946:glycocyamine; D000109:Acetylcholine; D005998:Glycine