S.04.04 Transient expression of phospho-acetylated form of histone H3 in medial prefrontal cortex of rats treated with MK-801

2009 ◽  
Vol 19 ◽  
pp. S181
Author(s):  
R. Guzik ◽  
M. Mackowiak ◽  
D. Dudys ◽  
K. Wedzony
2013 ◽  
Vol 65 (5) ◽  
pp. 1112-1123 ◽  
Author(s):  
Marzena Maćkowiak ◽  
Rafał Guzik ◽  
Dorota Dudys ◽  
Ewelina Bator ◽  
Krzysztof Wędzony

2019 ◽  
Vol 237 (1) ◽  
pp. 231-248 ◽  
Author(s):  
Joachim Latusz ◽  
Marzena Maćkowiak

Abstract Rationale Several findings indicate that early-life dysfunction of N-methyl-d-aspartate (NMDA) receptors might cause schizophrenia-like abnormalities in adulthood that might be induced by impairments in epigenetic regulation. Objectives In the present study, we investigated whether postnatal blockade of NMDA receptors (within the first 3 weeks of life) by the competitive antagonist CGP 37849 (CGP) might affect some epigenetic markers in the adult medial prefrontal cortex (mPFC). Methods Histone H3 phosphorylation at serine 10 (H3S10ph), histone H3 acetylation at lysine 9 or 14 (H3K9ac or H3K14ac, respectively), or expression of histone deacetylase (HDAC) 2, HDAC5, myocyte enhancer factor (MEF) 2D and activity-regulated cytoskeleton-associated protein (Arc) were analysed. Moreover, we also evaluated whether the deacetylase inhibitor sodium butyrate (SB; 1.2 mg/kg, ip) could prevent behavioural and neurochemical changes in the mPFC induced by CGP during memory retrieval in the trace fear conditioning paradigm. Results The results showed that CGP administration increased the number of H3S10ph nuclei but did not affect H3K9ac and H3K14ac or HDAC2 protein levels. However, CGP administration altered the HDAC5 mRNA and protein levels and increased the mRNA and protein levels of MEF2D. CGP also increased Arc mRNA, which was correlated with an increase in the amount of Arc DNA bound to MEF2D. SB given 2 h after training prevented impairment of the freezing response and disruption of epigenetic markers (H3S10ph, HDAC5, MEF2D) and Arc expression during memory retrieval induced by CGP administration. Conclusions The early-life blockade of NMDA receptors impairs some epigenetic regulatory processes in the mPFC that are involved in fear memory formation.


Synapse ◽  
2014 ◽  
Vol 68 (5) ◽  
pp. 202-208 ◽  
Author(s):  
Takashi Uehara ◽  
Tomiki Sumiyoshi ◽  
Dan Rujescu ◽  
Just Genius ◽  
Tadasu Matsuoka ◽  
...  

Author(s):  
Alessandro Piva ◽  
Lucia Caffino ◽  
Francesca Mottarlini ◽  
Nicholas Pintori ◽  
Fernando Castillo Díaz ◽  
...  

AbstractKetamine and MK-801 by blocking NMDA receptors may induce reinforcing effects as well as schizophrenia-like symptoms. Recent results showed that ketamine can also effectively reverse depressive signs in patients’ refractory to standard therapies. This evidence clearly points to the need of characterization of effects of these NMDARs antagonists on relevant brain areas for mood disorders. The aim of the present study was to investigate the molecular changes occurring at glutamatergic synapses 24 h after ketamine or MK-801 treatment in the rat medial prefrontal cortex (mPFC) and hippocampus (Hipp). In particular, we analyzed the levels of the glutamate transporter-1 (GLT-1), NMDA receptors, AMPA receptors subunits, and related scaffolding proteins. In the homogenate, we found a general decrease of protein levels, whereas their changes in the post-synaptic density were more complex. In fact, ketamine in the mPFC decreased the level of GLT-1 and increased the level of GluN2B, GluA1, GluA2, and scaffolding proteins, likely indicating a pattern of enhanced excitability. On the other hand, MK-801 only induced sparse changes with apparently no correlation to functional modification. Differently from mPFC, in Hipp, both substances reduced or caused no changes of glutamate receptors and scaffolding proteins expression. Ketamine decreased NMDA receptors while increased AMPA receptors subunit ratios, an effect indicative of permissive metaplastic modulation; conversely, MK-801 only decreased the latter, possibly representing a blockade of further synaptic plasticity. Taken together, these findings indicate a fine tuning of glutamatergic synapses by ketamine compared to MK-801 both in the mPFC and Hipp.


2014 ◽  
Vol 24 (2) ◽  
pp. 271-289 ◽  
Author(s):  
Marzena Maćkowiak ◽  
Ewelina Bator ◽  
Joachim Latusz ◽  
Patrycja Mordalska ◽  
Krzysztof Wędzony

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