Enhanced hippocampal long-term potentiation in rats after chronic exposure to homocysteine.
Homocysteine (HCY) is a sulphur-containing amino acid, which has been linked to neurodegenerative diseases such as Alzheimer's disease, and is widely reported to enhance vulnerability of neurons to oxidative, excitotoxic and apoptotic injury via perturbed calcium homeostasis, activation of N-methyl-D-aspartate (NMDA) and metabotropic glutamate (mGlu) receptors. The present study was undertaken to investigate the effects of HCY on long-term potentiation (LTP) and synaptic transmission after chronic 4-week systemic exposure to HCY in adult rats, and possible longer-term effects of HCY 4 weeks after exposure had ended. Contrary to expectation, LTP was enhanced, not retarded after chronic HCY exposure relative to controls. Basic synaptic transmission was not affected at this time point. However, after the 4-week wash out period, a decrease in speed of basic synaptic transmission emerged, and LTP was still partially enhanced, particularly for time points >30 min post-tetanus. In summary, we provide first evidence for sustained HCY-induced changes in hippocampal plasticity and a slow-onset disruption in synaptic transmission. These changes may reflect the suggested (excito-)toxicity of HCY and its putative contribution to neurodegenerative disease.
Christie
Louisa A
LA
School of Medical Sciences, College of Life Sciences and Medicine, Institute of Medical Sciences, University of Aberdeen, Foresterhill, Aberdeen AB25 2ZD, Scotland, UK.
Riedel
Gernot
G
Algaidi
Sami A
SA
Whalley
Lawrence J
LJ
Platt
Bettina
B
D000818:Animals; D006624:Hippocampus / Q000187:drug effects* / Q000502:physiology; D006710:Homocysteine / Q000494:pharmacology*; D017774:Long-Term Potentiation / Q000187:drug effects* / Q000502:physiology; D008297:Male; D009473:Neuronal Plasticity / Q000187:drug effects* / Q000502:physiology; D051381:Rats; D009435:Synaptic Transmission / Q000187:drug effects* / Q000502:physiology; D013997:Time Factors
D006710:Homocysteine