Profile of glutamate uptake and cellular viability in hippocampal slices exposed to oxygen and glucose deprivation: developmental aspects and protection by guanosine.
Stroke syndromes are a major cause of disability in middle and later life resulting in severe neuronal degeneration and loss of brain functions. In situations with energy failure, glutamate transport is impaired and high levels of this amino acid accumulate on the synaptic cleft. Our group has showed that guanosine exerts neuroprotection against neurotoxicity situations. The aim of this work is draw a post-ischemic profile of glutamate uptake and cell damage using an oxygen and glucose deprivation model (OGD) in hippocampal slices from young (P10) and adult (P60) rats, analyzing guanosine effect. OGD decreases glutamate uptake in both ages and recovery times, although decrease in cell viability was only observed 1 and 3 h after OGD in young and adult animals, respectively. Guanosine partially protected cell damage from 1 h in P10 and at 3 h in P60 rats and avoided glutamate uptake decrease from P10 rats at 3 h. The impairment of glutamate transporters since immediately after the insult observed here is probably due to an energetic failure; loss of cell viability was only observed from 1 h after OGD. The mechanism by which guanosine acts in the 'ischemic' model used here is still unknown, but evidence leads to its antiapoptotic effect.
Departamento de Bioquímica, Instituto de Ciências Básicas da Saúde, Universidade Federal do Rio Grande do Sul, UFRGS, Ramiro Barcelos, Porto Alegre, RS, Brazil. athomazi2000@hotmail.com
Ana Paula
AP
Thomazi
Bruna
B
Boff
Tales D
TD
Pires
Graça
G
Godinho
Cintia E
CE
Battú
Carmem
C
Gottfried
Diogo O
DO
Souza
Christianne
C
Salbego
Susana T
ST
Wofchuk
D000375:Aging / Q000378:metabolism*; D027322:Amino Acid Transport System X-AG / Q000187:drug effects / Q000378:metabolism; D000818:Animals; D000831:Animals, Newborn; D001693:Biological Transport, Active / Q000187:drug effects / Q000502:physiology; D020520:Brain Infarction / Q000188:drug therapy / Q000378:metabolism / Q000503:physiopathology; D002470:Cell Survival / Q000187:drug effects / Q000502:physiology; D004734:Energy Metabolism / Q000187:drug effects / Q000502:physiology; D018698:Glutamic Acid / Q000378:metabolism*; D006151:Guanosine / Q000378:metabolism* / Q000494:pharmacology; D006624:Hippocampus / Q000254:growth & development* / Q000378:metabolism* / Q000503:physiopathology; D020925:Hypoxia-Ischemia, Brain / Q000188:drug therapy / Q000378:metabolism* / Q000503:physiopathology; D008297:Male; D009474:Neurons / Q000187:drug effects / Q000378:metabolism; D018696:Neuroprotective Agents / Q000378:metabolism / Q000494:pharmacology; D009924:Organ Culture Techniques; D051381:Rats; D017208:Rats, Wistar
D027322:Amino Acid Transport System X-AG; D018696:Neuroprotective Agents; D006151:Guanosine; D018698:Glutamic Acid