Hippocampal synaptic plasticity is impaired in the Mecp2-null mouse model of Rett syndrome

Asaka, Yukiko; Jugloff, Denis G.M.; Zhang, Liang; Eubanks, James H.; Fitzsimonds, Reiko Maki

doi:10.1016/j.nbd.2005.07.005

Cited by 291 publications

(300 citation statements)

References 34 publications

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“…114 Similarly, impaired synaptic plasticity has been reported for hippocampus, and motor and sensory cortex, in Mecp2 308/y mice. 81 MECP2 has been linked to both DNA methylation and histone deacetylation, 115 two processes which regulate transcription in brain.…”

Section: Mouse Models Of Genetic Clinical Disorders With Autism Symptmentioning

confidence: 73%

Advances in behavioral genetics: mouse models of autism

2007

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Autism is a neurodevelopmental syndrome with markedly high heritability. The diagnostic indicators of autism are core behavioral symptoms, rather than definitive neuropathological markers. Etiology is thought to involve complex, multigenic interactions and possible environmental contributions. In this review, we focus on genetic pathways with multiple members represented in autism candidate gene lists. Many of these pathways can also be impinged upon by environmental risk factors associated with the disorder. The mouse model system provides a method to experimentally manipulate candidate genes for autism susceptibility, and to use environmental challenges to drive aberrant gene expression and cell pathology early in development. Mouse models for fragile X syndrome, Rett syndrome and other disorders associated with autistic-like behavior have elucidated neuropathology that might underlie the autism phenotype, including abnormalities in synaptic plasticity. Mouse models have also been used to investigate the effects of alterations in signaling pathways on neuronal migration, neurotransmission and brain anatomy, relevant to findings in autistic populations. Advances have included the evaluation of mouse models with behavioral assays designed to reflect disease symptoms, including impaired social interaction, communication deficits and repetitive behaviors, and the symptom onset during the neonatal period. Research focusing on the effect of gene-by-gene interactions or genetic susceptibility to detrimental environmental challenges may further understanding of the complex etiology for autism.

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Section: Mouse Models Of Genetic Clinical Disorders With Autism Symptmentioning

confidence: 73%

Advances in behavioral genetics: mouse models of autism

2007

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“…For example, chronic ethanol treatment, which induces amnesia (Brioni et al 1989), up-regulates the expression of the NMDA receptor in vitro and in vivo (Henniger et al 2003;Kalluri et al 1998). Memory behavior is impaired in the Rett syndrome mice model even though hippocampal NR2B expression is increased (Asaka et al 2006).…”

Section: Discussionmentioning

confidence: 99%

Accumulated hippocampal formaldehyde induces age-dependent memory decline

Tong

Han

Luo

et al. 2012

AGE

170

151

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Aging is an important factor in memory decline in aged animals and humans and in Alzheimer's disease and is associated with the impairment of hippocampal long-term potentiation (LTP) and downregulation of NR1/NR2B expression. Gaseous formaldehyde exposure is known to induce animal memory loss and human cognitive decline; however, it is unclear whether the concentrations of endogenous formaldehyde are elevated in the hippocampus and how excess formaldehyde affects LTP and memory formation during the aging process. In the present study, we report that hippocampal formaldehyde accumulated in memorydeteriorating diseases such as age-related dementia. Spatial memory performance was gradually impaired in normal Sprague-Dawley rats by persistent intraperitoneal injection with formaldehyde. Furthermore, excess formaldehyde treatment suppressed the hippocampal LTP formation by blocking N-methyl-D-aspartate (NMDA) receptor. Chronic excess formaldehyde treatment over a period of 30 days markedly decreased the viability of the hippocampus and down-regulated the expression of the NR1 and NR2B subunits of the NMDA receptor. Our results indicate that excess endogenous formaldehyde is a critical factor in memory loss in age-related memory-deteriorating diseases.

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“…Conversely, a facilitation in the second response would suggest a decreased probability of neurotransmitter release therefore residual calcium from the first stimulation presumably would contribute to the magnitude of the second response (Citri and Malenka, 2008). Loss-of-Mecp2 function has been associated with reduced paired pulse ratios and faster excitatory postsynaptic response depression, measures of short-term synaptic plasticity (Asaka et al, 2006;Moretti et al, 2006;Nelson et al, 2006). Alternatively, gain-of-Mecp2 function has been shown to augment paired pulse responses (Collins et al, 2004;Na et al, 2012) suggesting a bidirectional relationship between short-term plasticity and MeCP2 levels in which MeCP2 levels directly affect either calcium concentration in the presynaptic terminal or perhaps may alter proteins involved in neurotransmitter release.…”

Section: Loss-or Gain-of-mecp2 Function Influences Synaptic Plasticitymentioning

confidence: 99%

The Impact of MeCP2 Loss- or Gain-of-Function on Synaptic Plasticity

Nelson

Kavalali³

et al. 2012

Neuropsychopharmacol

151

116

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Methyl-CpG-binding protein 2 (MeCP2) is a transcriptional regulator of gene expression that is an important epigenetic factor in the maintenance and development of the central nervous system. The neurodevelopmental disorders Rett syndrome and MECP2 duplication syndrome arise from loss-of-function and gain-of-function alterations in MeCP2 expression, respectively. Several animal models have been developed to recapitulate the symptoms of Rett syndrome and MECP2 duplication syndrome. Cell morphology, neurotransmission, and cellular processes that support learning and memory are compromised as a result of MeCP2 loss-or gain-of-function. Interestingly, loss-of-MeCP2 function and MeCP2 overexpression trigger diametrically opposite changes in synaptic transmission. These findings indicate that the precise regulation of MeCP2 expression is a key requirement for the maintenance of synaptic and neuronal homeostasis and underscore its importance in central nervous system function. This review highlights the functional role of MeCP2 in the brain as a regulator of synaptic and neuronal plasticity as well as its etiological role in the development of Rett syndrome and MECP2 duplication syndrome.

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Hippocampal synaptic plasticity is impaired in the Mecp2-null mouse model of Rett syndrome

Cited by 291 publications

References 34 publications

Advances in behavioral genetics: mouse models of autism

Advances in behavioral genetics: mouse models of autism

Accumulated hippocampal formaldehyde induces age-dependent memory decline

The Impact of MeCP2 Loss- or Gain-of-Function on Synaptic Plasticity

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