On the mechanisms of neuroprotection by creatine and phosphocreatine

• DOI: 10.1046/j.1471-4159.2001.00052.x
• Publication Date: 2003-03-12T06:50:39Z
• Authors: Nickolay Brustove...; Tatiana Brustovetsky; Janet M. Dubinsky
• Keywords: Creatine

Creatine and phosphocreatine were evaluated for their ability to prevent death of cultured striatal hippocampal neurons exposed either glutamate or 3‐nitropropionic acid (3NP) inhibit the mitochondrial permeability transition in CNS mitochondria. Phosphocreatine (PCr), a lesser extent creatine (Cr), but not (5R,10S)‐(+)‐5‐methyl‐10,11‐dihydro‐5H‐dibenzo[a,d]cyclohepten‐5,10‐imine hydrogen maleate (MK801), dose‐dependently ameliorated 3NP toxicity when applied simultaneously with Mg 2+ ‐free media. Pre‐treatment PCr 2 5 days Cr protected against excitotoxicity equivalent that achieved by MK801 post‐treatment. The combination pre‐treatment post‐treatment did provide additional protection, indicating both prevented attributable secondary release. To determine if directly inhibited transition, swelling depolarization assayed isolated, purified brain reduced amount induced calcium 20%. decreased inhibitors kinase octamer–dimer present. However, mitochondria prepared from rats fed diet supplemented 2% weeks, calcium‐induced was altered. Thus, neuroprotective properties may reflect enhancement cytoplasmic high‐energy phosphates inhibition.