Changes in Synaptic Transmission and Long-term Potentiation Induction as a Possible Mechanism for Learning Disability in an Animal Model of Multiple Sclerosis
2
조회
0
다운로드
0
인용
0
참고문헌
키워드
초록
Purpose: Multiple sclerosis (MS) is a chronic inflammatory demyelinating disease of the central nervous system. It has been shown that memory deficits is common in patients with MS. Recent studies using experimental autoimmune encephalomyelitis (EAE) as an animal model of MS have shown that indicated that EAE causes hippocampal-dependent impairment in learning and memory. Thus far, there have been no in vivo electrophysiological reports describing synaptic transmission in EAE animals. The aim of the present work is to evaluate the synaptic changes in the CA1 region of the hippocampus of EAE rats. Methods: To evaluate changes in synaptic transmission in the CA1 region of the hippocampus of EAE rats, field excitatory postsynaptic potentials (fEPSPs) from the stratum radiatum of CA1 neurons, were recorded following Schaffer collateral stimulation. Results: The results showed that EAE causes deficits in synaptic transmission and long-term potentiation (LTP) in the hippocampus. In addition, paired-pulse index with a 120 msec interstimulus interval was decreased in the EAE group. These findings indicate that EAE might induce suppression in synaptic transmission and LTP by increasing the inhibitory effect of GABAB receptors on the glutamate-mediated EPSP. Conclusions: In conclusion, influence of inflammation-triggered mechanisms on synaptic transmission may explain the negative effect of EAE on learning abilities in rats.
Abstract
Purpose: Multiple sclerosis (MS) is a chronic inflammatory demyelinating disease of the central nervous system. It has been shown that memory deficits is common in patients with MS. Recent studies using experimental autoimmune encephalomyelitis (EAE) as an animal model of MS have shown that indicated that EAE causes hippocampal-dependent impairment in learning and memory. Thus far, there have been no in vivo electrophysiological reports describing synaptic transmission in EAE animals. The aim of the present work is to evaluate the synaptic changes in the CA1 region of the hippocampus of EAE rats. Methods: To evaluate changes in synaptic transmission in the CA1 region of the hippocampus of EAE rats, field excitatory postsynaptic potentials (fEPSPs) from the stratum radiatum of CA1 neurons, were recorded following Schaffer collateral stimulation. Results: The results showed that EAE causes deficits in synaptic transmission and long-term potentiation (LTP) in the hippocampus. In addition, paired-pulse index with a 120 msec interstimulus interval was decreased in the EAE group. These findings indicate that EAE might induce suppression in synaptic transmission and LTP by increasing the inhibitory effect of GABAB receptors on the glutamate-mediated EPSP. Conclusions: In conclusion, influence of inflammation-triggered mechanisms on synaptic transmission may explain the negative effect of EAE on learning abilities in rats.
참고문헌 (21)
- Lassmann H, "Heterogeneity of multiple sclerosis pathogenesis: implications for diagnosis and therapy", Trends Mol Med, 7, pp.115~121 (2001)
- Calabrese P, "Neuropsychology of multiple sclerosis: an overview", J Neurol, 253(Suppl 1), pp.I10~I15 (2006)
- Rao SM, "Cognitive dysfunction in multiple sclerosis. I. Frequency, patterns, and prediction", Neurology, 41, pp.685~691 (1991)
- Vereker E, "The inhibitory effect of interleukin-1beta on long-term potentiation is coupled with increased activity of stress-activated protein kinases", J Neurosci, 20, pp.6811~6819 (2000)
- Papadopoulos D, "Substantial archaeocortical atrophy and neuronal loss in multiple sclerosis", Brain Pathol, 19, pp.238~253 (2009)
- Sicotte NL, "Regional hippocampal atrophy in multiple sclerosis", Brain, 131(Pt 4), pp.1134~1141 (2008)
- Ziehn MO, "Hippocampal CA1 atrophy and synaptic loss during experimental autoimmune encephalomyelitis, EAE", Lab Invest, 90, pp.774~ (2010)
- Di Filippo M, "Effects of central and peripheral inflammation on hippocampal synaptic plasticity", Neurobiol Dis, 52, pp.229~236 (2013)
- Yorns WR Jr, "Frequency-dependent changes in the paired-pulse index in the hippocampus of the freely moving adult male rat", Exp Neurol, 186, pp.104~108 (2004)
- Ziehn MO, "Therapeutic testosterone administration preserves excitatory synaptic transmission in the hippocampus during autoimmune demyelinating disease", J Neurosci, 32, pp.12312~12324 (2012)
- Prochnow N, "An electrophysiologic approach to quantify impaired synaptic transmission and plasticity in experimental autoimmune encephalomyelitis", J Neuroimmunol, 264, pp.48~53 (2013)
- Centonze D, "Inflammation triggers synaptic alteration and degeneration in experimental autoimmune encephalomyelitis", J Neurosci, 29, pp.3442~3452 (2009)
- Uzawa A, "Anti-N-methyl D-aspartate-type glutamate receptor antibody-positive limbic encephalitis in a patient with multiple sclerosis", Clin Neurol Neurosurg, 114, pp.402~404 (2012)
- Pruss H, "Retrospective analysis of NMDA receptor antibodies in encephalitis of unknown origin", Neurology, 75, pp.1735~1739 (2010)
- Nistico R, "Synaptic plasticity in multiple sclerosis and in experimental autoimmune encephalomyelitis", Philos Trans R Soc Lond B Biol Sci, 369, pp.20130162~ (2013)
- Chu Z, "GABA(B) receptor-mediated heterosynaptic depression of excitatory synaptic transmission in rat frontal neocortex", Brain Res, 959, pp.39~49 (2003)
- Karnup S, "Temporal overlap of excitatory and inhibitory afferent input in guinea-pig CA1 pyramidal cells", J Physiol, 516(Pt 2), pp.485~504 (1999)
- Davies CH, "Paired-pulse depression of monosynaptic GABA-mediated inhibitory postsynaptic responses in rat hippocampus", J Physiol, 424, pp.513~531 (1990)
- Zeng X, "Depression of early and late monosynaptic inhibitory postsynaptic potentials in hippocampal CA1 neurons following prolonged benzodiazepine administration: role of a reduction in Cl- driving force", Synapse, 25, pp.125~136 (1997)
- Lanthorn TH, "Baclofen selectively inhibits excitatory synaptic transmission in the hippocampus", Brain Res, 225, pp.171~178 (1981)
- Potier B, "Presynaptic inhibitory effect of baclofen on hippocampal inhibitory synaptic transmission involves a pertussis toxin-sensitive G-protein", Eur J Pharmacol, 231, pp.427~433 (1993)