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Effects of chronic REM sleep restriction on D1 receptor and related signal pathways in rat prefrontal cortex.

Han Y, Wen X, Rong F, Chen X, Ouyang R, Wu S, Nian H, Ma W - Biomed Res Int (2015)

Bottom Line: The aim of the present study was to investigate the effect of chronic REM sleep restriction (REM-CSR) on the D1 receptor (D1R) and key molecules in D1R' signal pathways in PFC.The expressions of genes and proteins of related molecules were assayed by real-time PCR and Western blot, respectively.The general state and morphology of PFC in rats were changed by CSR, and DA level and the expression of D1R in PFC were markedly decreased (P < 0.01, P < 0.05); the expression of phosphor-PKAcα was significantly lowered in CSR rats (P < 0.05).

View Article: PubMed Central - PubMed

Affiliation: Department of Neurology, Changhai Hospital, Second Military Medical University, Shanghai 200433, China.

ABSTRACT
The prefrontal cortex (PFC) mediates cognitive function that is sensitive to disruption by sleep loss, and molecular mechanisms regulating neural dysfunction induced by chronic sleep restriction (CSR), particularly in the PFC, have yet to be completely understood. The aim of the present study was to investigate the effect of chronic REM sleep restriction (REM-CSR) on the D1 receptor (D1R) and key molecules in D1R' signal pathways in PFC. We employed the modified multiple platform method to create the REM-CSR rat model. The ultrastructure of PFC was observed by electron microscopy. HPLC was performed to measure the DA level in PFC. The expressions of genes and proteins of related molecules were assayed by real-time PCR and Western blot, respectively. The general state and morphology of PFC in rats were changed by CSR, and DA level and the expression of D1R in PFC were markedly decreased (P < 0.01, P < 0.05); the expression of phosphor-PKAcα was significantly lowered in CSR rats (P < 0.05). The present results suggested that the alteration of neuropathology and D1R expression in PFC may be associated with CSR induced cognitive dysfunction, and the PKA pathway of D1R may play an important role in the impairment of advanced neural function.

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Related in: MedlinePlus

The scheme of signal pathways of D1R. This simplified view of the signal pathways shows major downstream mediators between the two major pathways of D1R. D1R regulates CREB through PKA pathway (expressed by purple molecules) and MAPK pathway (yellow members), and the key molecules are marked by red. CREB was significantly decreased by CSR, while PKA showed a notable reduction (expressed by downward arrow).
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fig4: The scheme of signal pathways of D1R. This simplified view of the signal pathways shows major downstream mediators between the two major pathways of D1R. D1R regulates CREB through PKA pathway (expressed by purple molecules) and MAPK pathway (yellow members), and the key molecules are marked by red. CREB was significantly decreased by CSR, while PKA showed a notable reduction (expressed by downward arrow).

Mentions: D1R regulates the nuclear transcription factor via two major pathways: PKA and MAPK pathways, and PKA and extracellular signal-regulated kinase (ERK1/2) are the key regulatory molecules in PKA and MAPK pathways, respectively (Figure 4). Studies have shown that the ability of D1R to increase both the persistence and early magnitude of long-term potentiation (LTP) was associated with activation of PKA pathway [29], and other researchers found that the decreased phosphorylation of DARPP-32 and CREB, which were also the key signal molecules in PKA pathway, was linked to the notable impairment of delayed spatial memory retrieval caused by selective D1R antagonist in the prefrontal cortex [28]. In many cases, ERK1/2 was involved in memory consolidation. Guan et al. [30] indicated that decreased ERK1/2 activation in the hippocampus was associated with sleep deprivation-induced spatial memory impairment, but the alterations of ERK1/2 were not observed in the cortex. In this study, we demonstrated that REM-CSR decreased the phosphorylation of PKA and CREB but did not alter the level of phosphor-ERK1/2 (Figure 4), suggesting that the reduction of DA concentration and D1R expression induced by REM-CSR might impair the function of PFC by repressing PKA pathway activity but not the MAPK pathway. These results provide new insights in the molecular mechanisms involved in D1R-dependent function modulation of PFC, where PKA pathway plays a pivotal role in the synthesis of CREB during REM-CSR.


Effects of chronic REM sleep restriction on D1 receptor and related signal pathways in rat prefrontal cortex.

Han Y, Wen X, Rong F, Chen X, Ouyang R, Wu S, Nian H, Ma W - Biomed Res Int (2015)

The scheme of signal pathways of D1R. This simplified view of the signal pathways shows major downstream mediators between the two major pathways of D1R. D1R regulates CREB through PKA pathway (expressed by purple molecules) and MAPK pathway (yellow members), and the key molecules are marked by red. CREB was significantly decreased by CSR, while PKA showed a notable reduction (expressed by downward arrow).
© Copyright Policy - open-access
Related In: Results  -  Collection

Show All Figures
getmorefigures.php?uid=PMC4352426&req=5

fig4: The scheme of signal pathways of D1R. This simplified view of the signal pathways shows major downstream mediators between the two major pathways of D1R. D1R regulates CREB through PKA pathway (expressed by purple molecules) and MAPK pathway (yellow members), and the key molecules are marked by red. CREB was significantly decreased by CSR, while PKA showed a notable reduction (expressed by downward arrow).
Mentions: D1R regulates the nuclear transcription factor via two major pathways: PKA and MAPK pathways, and PKA and extracellular signal-regulated kinase (ERK1/2) are the key regulatory molecules in PKA and MAPK pathways, respectively (Figure 4). Studies have shown that the ability of D1R to increase both the persistence and early magnitude of long-term potentiation (LTP) was associated with activation of PKA pathway [29], and other researchers found that the decreased phosphorylation of DARPP-32 and CREB, which were also the key signal molecules in PKA pathway, was linked to the notable impairment of delayed spatial memory retrieval caused by selective D1R antagonist in the prefrontal cortex [28]. In many cases, ERK1/2 was involved in memory consolidation. Guan et al. [30] indicated that decreased ERK1/2 activation in the hippocampus was associated with sleep deprivation-induced spatial memory impairment, but the alterations of ERK1/2 were not observed in the cortex. In this study, we demonstrated that REM-CSR decreased the phosphorylation of PKA and CREB but did not alter the level of phosphor-ERK1/2 (Figure 4), suggesting that the reduction of DA concentration and D1R expression induced by REM-CSR might impair the function of PFC by repressing PKA pathway activity but not the MAPK pathway. These results provide new insights in the molecular mechanisms involved in D1R-dependent function modulation of PFC, where PKA pathway plays a pivotal role in the synthesis of CREB during REM-CSR.

Bottom Line: The aim of the present study was to investigate the effect of chronic REM sleep restriction (REM-CSR) on the D1 receptor (D1R) and key molecules in D1R' signal pathways in PFC.The expressions of genes and proteins of related molecules were assayed by real-time PCR and Western blot, respectively.The general state and morphology of PFC in rats were changed by CSR, and DA level and the expression of D1R in PFC were markedly decreased (P < 0.01, P < 0.05); the expression of phosphor-PKAcα was significantly lowered in CSR rats (P < 0.05).

View Article: PubMed Central - PubMed

Affiliation: Department of Neurology, Changhai Hospital, Second Military Medical University, Shanghai 200433, China.

ABSTRACT
The prefrontal cortex (PFC) mediates cognitive function that is sensitive to disruption by sleep loss, and molecular mechanisms regulating neural dysfunction induced by chronic sleep restriction (CSR), particularly in the PFC, have yet to be completely understood. The aim of the present study was to investigate the effect of chronic REM sleep restriction (REM-CSR) on the D1 receptor (D1R) and key molecules in D1R' signal pathways in PFC. We employed the modified multiple platform method to create the REM-CSR rat model. The ultrastructure of PFC was observed by electron microscopy. HPLC was performed to measure the DA level in PFC. The expressions of genes and proteins of related molecules were assayed by real-time PCR and Western blot, respectively. The general state and morphology of PFC in rats were changed by CSR, and DA level and the expression of D1R in PFC were markedly decreased (P < 0.01, P < 0.05); the expression of phosphor-PKAcα was significantly lowered in CSR rats (P < 0.05). The present results suggested that the alteration of neuropathology and D1R expression in PFC may be associated with CSR induced cognitive dysfunction, and the PKA pathway of D1R may play an important role in the impairment of advanced neural function.

Show MeSH
Related in: MedlinePlus