In Vivo Development of Brain Phosphocreatine in Normal and Creatine‐Treated Rabbit Pups

Abstract

Abstract:To study the effects of creatine (Cr) on brain energy metabolism and on hypoxia-induced seizures, 5-to 30-day-old rabbit pups were given subcutaneous Cr (3 g/kg) for 3 days before exposure to 4% O 2 for 8 min. In saline-treated controls, hypoxic seizures were most frequent at 15 days (80% of pups) and 20 days (60%) of age. Seizures were prevented at 15 days and reduced 60% at 20 days in Cr-treated pups. In surface coil-localized brain 31 P nuclear magnetic resonance spectra, with signal from both cerebral gray (GM) and white (WM) matter, the phosphocreatine (PCr)/nucleoside triphosphate (NTP) ratio doubled between 5 and 30 days of age in controls. In all Cr-injected pups, brain PCr/NTP increased to values seen in 30-day-old controls. When spectra were acquired in predominantly GM and WM slices in vivo, the PCr/NTP ratio was very low in GM at 5 days but reached adult levels by 15 days in controls. In WM, the ratio increased steadily from 5 to 30 days of age. In Cr-injected pups, PCr/NTP increased to mature levels in WM and in GM at all ages. In conclusion, hypoxic seizures occur midway in the time course of brain PCr/NTP increase in rabbit pups as previously described in rat pups. In both altricial pups, systemic Cr increases brain PCr/NTP ratio and prevents hypoxic seizures. These results suggest that mature levels of PCr and/or Cr in brain limit EEG activation either directly or indirectly by preventing hypoxic metabolic changes. Key Words: Creatine-Development-Seizures-Brain phosphocreatine-HypoxiaNuclear magnetic resonance spectroscopy.

Efeitos da suplementação oral com creatina sobre o metabolismo e a morfologia hepática em ratos

“…Esses trabalhos também apresentam que essa necessidade diária de creatina é suprida por síntese endógena, tendo como pressuposto a ingestão de alimentos que contenham os aminoácidos necessários para a síntese de creatina (1,2) . Entretanto, a necessidade de creatina em atletas e em casos patológicos pode estar aumentada (1,(8)(9)(10)(11)(12) . Por exemplo, doenças na qual a função mitocondrial está alterada, resultando numa diminuição da síntese de adenosina trifosfato, como no caso da doença de Parkinson, Huntington e miopatias, a suplementação com creatina tem apresentado importantes efeitos benéficos (12) .…”

“…O conteúdo celular de creatina pode variar de acordo com a dieta e principalmente decorrente do uso de suplementos alimentares a base de creatina (6,7) . A diminuição dos níveis teciduais de creatina tem sido associada a uma série de doenças, razão pela qual os efeitos da suplementação vem sendo estudados, tanto em modelos experimentais quanto em estudos clínicos (8)(9)(10)(11) . Se por um lado a suplementação com creatina apresenta efeitos benéficos, por outro, alguns trabalhos experimentais e clínicos têm associado à sua suplementação à alguns efeitos colaterais, particularmente sobre o fígado e rins (13)(14)(15)(16)(17) .…”

Brain Creatine Kinase and Creatine Transporter Proteins in Normal and Creatine-Treated Rabbit Pups

“…Hypoxia causes seizures in rat and rabbit pups at ages when brain PCr/NTP ratio has increased about 50% [15,17]. These hypoxia-induced seizures are blocked by Cr with an associated increase in PCr/NTP ratio in both species.…”

“…Piglet and rabbit brains show higher PCr concentration, and lower Mi-CK activity and Cr content in white matter compared to gray matter [4,5,10,11]. Developmentally, brain PCr/nucleoside triphosphate (NTP) ratio increases between 5 and 25 postnatal days in rat and between 5 and 30 days in rabbit, probably due to increased PCr in both species [12][13][14][15]. This increase is coincident with the increase in aerobic glycolysis in rat brain [16].…”

“…In the rabbit, the in vivo 31 P nuclear magnetic resonance (NMR) PCr signal first appears in white matter, but reaches mature levels at an earlier age in gray matter. Injecting Cr to rabbit pups at ages between 5 and 30 days increases PCr to adult levels in white matter and above adult levels in gray matter [15]. While the mechanism by which Cr blocks seizures is unknown, recent evidence suggests that the brain CK system plays an important role in regulating ATP metabolism and in metabolic adaptation during hypoxia and seizures [18,19].…”