Severe Hyperhomocysteinemia Decreases Creatine Kinase Activity and Causes Memory Impairment: Neuroprotective Role of Creatine.

Abstract

In the present study, we investigate the effect of severe hyperhomocysteinemia on biochemical (creatine kinase activity), behavioral (memory tests), and histological assessments (hippocampal volume). A possible neuroprotective role of creatine on hyperhomocysteinemia effects was also evaluated. Severe hyperhomocysteinemia was induced in neonate rats (starting at 6 days of age) by treatment with homocysteine (0.3-0.6 μmol/g body weight) for 23 days. Creatine (50 mg/kg body weight) was administered concomitantly with homocysteine. Controls received saline in the same volumes. Twelve hours after the last injection, the rats were submitted to behavioral tests [(recognition task (NOR)] and inhibitory avoidance (IA)]. Following behavioral assessment, the animals were perfused and decapitated, the brain removed for subsequent morphological analysis of the hippocampus. Another group of animals was used to test creatine kinase activity in hippocampus. The results showed that rats treated with homocysteine decreased (44%) the exploration of the novel object in NOR. In the IA task, homocysteine-treated animals presented decreased latencies to step down the platform in short- (32%) and long-term (18%) testings (3 h and 7 days, respectively), evidencing aversive memory impairment. Hippocampal volume was not altered by homocysteine administration. Hyperhomocysteinemia decreased (45%) creatine kinase activity, and creatine was able to prevent such effect probably by creatine kinase/phosphocreatine/creatine homeostasis, which serves as energy circuit within of the cell. This finding may be associated, at least in part, with memory improvement, suggesting that creatine might represent an effective adjuvant to protect against the effects of high homocysteine plasma levels.

• Authors: Janaína Kolling, Aline Longoni, Cassiana Siebert, Tiago Marcon Dos Santos, Eduardo Peil Marques, Jaqueline Carletti, Lenir Orlandi Pereira, Angela T S Wyse
• Journal: Neurotoxicity research (Neurotox Res) Vol. 32 Issue 4 Pg. 585-593 (Nov 2017) ISSN: 1476-3524 [Electronic] United States
• PMID: 28656547 (Publication Type: Journal Article)

Chemical References

• Creatine Kinase
• Creatine

Topics

• Animals
• Creatine (pharmacology)
• Creatine Kinase (drug effects)
• Female
• Hippocampus (drug effects)
• Homeostasis (drug effects)
• Hyperhomocysteinemia (chemically induced, drug therapy)
• Male
• Memory (drug effects)
• Memory Disorders (prevention & control)
• Neuroprotection (drug effects)
• Phosphorylation
• Rats, Wistar