scholarly journals lncRNA Neat1 drives neuronal histone methylation and age-related memory impairments

2019 ◽  
Author(s):  
Anderson A. Butler ◽  
Daniel R. Johnston ◽  
Simranjit Kaur ◽  
Farah D. Lubin
Keyword(s):  
Histone Methylation ◽  
Transcriptional Repression ◽  
Rna Binding ◽  
Gene Activation ◽  
Memory Formation ◽  
Long Term Memory ◽  
Mrna Levels ◽  
Term Memory ◽  
Age Related

AbstractHistone methylation is critical for the formation and maintenance of long-term memories. Long noncoding RNAs (lncRNAs) are regulators of histone methyltransferases and other chromatin modifying enzymes (CMEs). We investigated how lncRNA Neat1-mediated histone methylation contributes to hippocampus-dependent long-term memory formation, using a combination of transcriptomics, RNA binding protein immunoprecipitation, CRISPR mediated gene activation, and behavioral approaches. Suppression of the lncRNA Neat1 revealed widespread changes in gene transcription as well as perturbations of histone 3 lysine 9 dimethylation (H3K9me2), a repressive histone modification mark that is dysregulated in the aging hippocampus. We identified a Neat1-dependent mechanism of transcriptional repression via H3K9me2 at the c-Fos promoter corresponding with observed changes in c-Fos mRNA levels. Overexpression of hippocampal Neat1 via CRISPRa is sufficient to impair memory formation in young adults, recapitulating observed memory deficits in old adults, while Neat1 suppression in both young and old adult mice improves memory. These results suggest that lncRNA Neat1 is a potent epigenetic regulator of hippocampus-dependent long-term memory formation.

scholarly journals Long noncoding RNA NEAT1 mediates neuronal histone methylation and age-related memory impairment

2019 ◽  
Vol 12 (588) ◽  
pp. eaaw9277 ◽  
Author(s):  
Anderson A. Butler ◽  
Daniel R. Johnston ◽  
Simranjit Kaur ◽  
Farah D. Lubin
Keyword(s):  
Histone Methylation ◽  
Noncoding Rna ◽  
Rna Binding ◽  
Memory Formation ◽  
Long Term Memory ◽  
Term Memory ◽  
Adult Mice ◽  
Old Adult ◽  
Lncrna Neat1

Histone methylation is critical for the formation and maintenance of long-term memories. Long noncoding RNAs (lncRNAs) are regulators of histone methyltransferases and other chromatin-modifying enzymes (CMEs), thereby epigenetically modifying gene expression. Here, we investigated how the lncRNA NEAT1 may epigenetically contribute to hippocampus-dependent, long-term memory formation using a combination of transcriptomics, RNA-binding protein immunoprecipitation, CRISPR-mediated gene activation (CRISPRa), and behavioral approaches. Knockdown of the lncRNA Neat1 revealed widespread changes in gene transcription, as well as perturbations of histone 3 lysine 9 dimethylation (H3K9me2), a repressive histone modification mark that was increased in the hippocampus of aging rodents. We identified a NEAT1-dependent mechanism of transcriptional repression by H3K9me2 at the c-Fos promoter, corresponding with observed changes in c-Fos mRNA expression. Overexpression of hippocampal NEAT1 using CRISPRa was sufficient to impair memory formation in young adult mice, recapitulating observed memory deficits in old adult mice, whereas knocking down NEAT1 in both young and old adult mice improved behavior test–associated memory. These results suggest that the lncRNA NEAT1 is an epigenetic suppressor of hippocampus-dependent, long-term memory formation.

scholarly journals Long term memory of configural learning is enhanced via CREB upregulation by the flavonoid Quercetin in Lymnaea stagnalis

2021 ◽  
Author(s):  
Anuradha Batabyal ◽  
Veronica Rivi ◽  
Cristina Benatti ◽  
Johanna MC Blom ◽  
Ken Lukowiak
Keyword(s):  
Heat Stress ◽  
Lymnaea Stagnalis ◽  
Memory Formation ◽  
Long Term Memory ◽  
Pond Snail ◽  
Mrna Levels ◽  
Term Memory ◽  
Configural Learning ◽  
Flavonoid Quercetin

Animals respond to acute stressors by modifying their behaviour and physiology. The pond snail Lymnaea stagnalis exhibits configural learning (CL), a form of higher order associative learning. In CL snails develop a landscape of fear when they experience a predatory cue along with a taste of food. This experience results in a suppression of the food response; but the memory only persists for 3h. Lymnaea has been also found to upregulate heat shock proteins (HSPs) as a result of acute heat stress that leads to the enhancement of memory formation. A plant flavonoid quercetin blocks the upregulation of HSPs when experienced prior to heat stress. Here we used this blocking mechanism to test the hypothesis that HSP upregulation played a critical role in CL. Snails experienced quercetin prior to CL training and surprisingly instead of blocking memory formation it enhanced the memory such that it now persisted for at least 24h. Quercetin exposure both prior to or post CL enhanced long-term memory (LTM) up to 48h. We quantified CREB1 mRNA levels in the Lymnaea central nervous system following quercetin and found LymCREB1 to be upregulated following quercetin exposure. The enhanced LTM phenotype in L. stagnalis was most pronounced when quercetin was experienced during the consolidation phase. Additionally, quercetin exposure during the memory reconsolidation phase also led to memory enhancement. Thus, we found no support of our original hypothesis but found that quercetin exposure upregulated LymCREB1 leading to LTM formation for CL.

scholarly journals Epigenetic regulation of the circadian genePer1in the hippocampus mediates age-related changes in memory and synaptic plasticity

2018 ◽  
Author(s):  
Janine L. Kwapis ◽  
Yasaman Alaghband ◽  
Enikö A. Kramár ◽  
Alberto J. López ◽  
Annie Vogel Ciernia ◽  
...  
Keyword(s):  
Synaptic Plasticity ◽  
Circadian Clock ◽  
Clock Gene ◽  
Memory Performance ◽  
Activity Patterns ◽  
Memory Formation ◽  
Long Term Memory ◽  
Term Memory ◽  
Age Related

AbstractAging is accompanied by impairments in both circadian rhythmicity and long-term memory. Although it is clear that memory performance is affected by circadian cycling, it is unknown whether age-related disruption of the circadian clock causes impaired hippocampal memory. Here, we show that the repressive histone deacetylase HDAC3 restricts long-term memory, synaptic plasticity, and learning-induced expression of the circadian genePer1in the aging hippocampus without affecting rhythmic circadian activity patterns. We also demonstrate that hippocampalPer1is critical for long-term memory formation. Together, our data challenge the traditional idea that alterations in the core circadian clock drive circadian-related changes in memory formation and instead argue for a more autonomous role for circadian clock gene function in hippocampal cells to gate the likelihood of long-term memory formation.

scholarly journals Disruption of the astrocyte–neuron interaction is responsible for the impairments in learning and memory in 5XFAD mice: an Alzheimer’s disease animal model

2021 ◽  
Vol 14 (1) ◽  
Author(s):  
Moonseok Choi ◽  
Sang-Min Lee ◽  
Dongsoo Kim ◽  
Heh-In Im ◽  
Hye-Sun Kim ◽  
...  
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Animal Model ◽  
Memory Formation ◽  
Long Term Memory ◽  
Term Memory ◽  
Stat3 Phosphorylation ◽  
Neuron Interactions ◽  
5Xfad Mice

AbstractThe morphological dynamics of astrocytes are altered in the hippocampus during memory induction. Astrocyte–neuron interactions on synapses are called tripartite synapses. These control the synaptic function in the central nervous system. Astrocytes are activated in a reactive state by STAT3 phosphorylation in 5XFAD mice, an Alzheimer’s disease (AD) animal model. However, changes in astrocyte–neuron interactions in reactive or resting-state astrocytes during memory induction remain to be defined. Here, we investigated the time-dependent changes in astrocyte morphology and the number of astrocyte–neuron interactions in the hippocampus over the course of long-term memory formation in 5XFAD mice. Hippocampal-dependent long-term memory was induced using a contextual fear conditioning test in 5XFAD mice. The number of astrocytic processes increased in both wild-type and 5XFAD mice during memory formation. To assess astrocyte–neuron interactions in the hippocampal dentate gyrus, we counted the colocalization of glial fibrillary acidic protein and postsynaptic density protein 95 via immunofluorescence. Both groups revealed an increase in astrocyte–neuron interactions after memory induction. At 24 h after memory formation, the number of tripartite synapses returned to baseline levels in both groups. However, the total number of astrocyte–neuron interactions was significantly decreased in 5XFAD mice. Administration of Stattic, a STAT3 phosphorylation inhibitor, rescued the number of astrocyte–neuron interactions in 5XFAD mice. In conclusion, we suggest that a decreased number of astrocyte–neuron interactions may underlie memory impairment in the early stages of AD.

scholarly journals Wnt Signaling Is Required for Long-Term Memory Formation

Cell Reports ◽  
2013 ◽  
Vol 4 (6) ◽  
pp. 1082-1089 ◽  
Author(s):  
Ying Tan ◽  
Dinghui Yu ◽  
Germain U. Busto ◽  
Curtis Wilson ◽  
Ronald L. Davis
Keyword(s):  
Wnt Signaling ◽  
Memory Formation ◽  
Long Term Memory ◽  
Term Memory

scholarly journals What's hot: the enhancing effects of thermal stress on long-term memory formation in Lymnaea stagnalis

2012 ◽  
Vol 215 (24) ◽  
pp. 4322-4329 ◽  
Author(s):  
M. L. Teskey ◽  
K. S. Lukowiak ◽  
H. Riaz ◽  
S. Dalesman ◽  
K. Lukowiak
Keyword(s):  
Thermal Stress ◽  
Lymnaea Stagnalis ◽  
Memory Formation ◽  
Long Term Memory ◽  
Term Memory
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