MicroRNA-132 (miR-132) has been demonstrated to affect multiple neuronal functions, including den... more MicroRNA-132 (miR-132) has been demonstrated to affect multiple neuronal functions, including dendritic growth and spinogenesis in cultured neurons and brain slices, as well as learning behavior of animals. However, its role in acquisition of temporal-associated memory remains unclear. In this study, we demonstrated that the mature miR-132 level in mouse hippocampus was significantly increased at 30 min after trace fear conditioning, a type of temporal-associated learning, and returned to baseline values in 2 h. We then knocked down miR-132 expression in vivo by infusing a lentivector expressing anti-miR-132 hairpin RNA into the third ventricle near the anterior hippocampi such RNA diffused laterally to both hippocampal formations, later confirmed by histological analysis. This approach successfully reduced hippocampal miR-132 expression in both naïve and trace fear conditioned groups, and impaired acquisition of trace fear memory in mice. To our knowledge, this result is the first demonstration of change in temporal learning behavior by reducing microRNA (miRNA) level specifically in the hippocampal region.
BackgroundThe relationship between neuronal inflammation and impairment of memory retrieval is no... more BackgroundThe relationship between neuronal inflammation and impairment of memory retrieval is not well established, partially because of the lack of appropriate compound to test this hypothesis. Here we investigated effects of a novel coral‐derived compound on hippocampal inflammation markers and contextual fear memory retrieval using a triple‐transgenic AD (3xTg‐AD) mouse modelMethodThe coral‐derived compound was administered to mice with intraperitoneal injection before subjected to trace fear conditioning. Expression of inflammation markers were measured by western blot analysis or flourescent immunihistochemijcal staining.ResultResults indicate that coral‐derived compound is effective on reducing expression levels of inflammatory markers including TNF‐α, COX‐2, and iNOS in the hippocamapal region, and increased expression of postsynaptic density protein‐95 (PSD‐95) in the hippocampus of 3xTg‐AD mice. It also increased dendritic spine density in hippocampus. Phenotypically, this...
ECa 233 is a standardized extract of Centella asiatica (CA), an herb widely used in traditional C... more ECa 233 is a standardized extract of Centella asiatica (CA), an herb widely used in traditional Chinese and Ayurvedic medicine. Previous studies reported that ECa 233 enhanced memory retention and synaptic plasticity in the hippocampus of healthy rats. Because of this, we became curious whether ECa 233 has a therapeutic effect on the fear memory deficit in the triple transgenic Alzheimer’s disease (3xTg-AD) model mice. Fear memory is a crucial emotional memory for survival that is found to be impaired in patients with early-onset Alzheimer’s disease (AD). In this study, we orally administered ECa 233 (doses: 10, 30, and 100[Formula: see text]mg/kg) to 3xTg-AD mice, who were five months old, for 30 consecutive days. We found that ECa 233 prevented a cued fear memory deficit and enhanced hippocampal long-term potentiation (LTP) in 3xTg-AD mice. Subsequent proteomic and western blot analyses revealed increased expression levels of the molecules related to LTP induction and maintenance,...
Age-related macular degeneration (AMD) is a progressive eye disease that causes irreversible impa... more Age-related macular degeneration (AMD) is a progressive eye disease that causes irreversible impairment of central vision, and effective treatment is not yet available. Extracellular accumulation of amyloid-beta (Aβ) in drusen that lie under the retinal pigment epithelium (RPE) has been reported as one of the early signs of AMD and was found in more than 60% of Alzheimer’s disease (AD) patients. Extracellular deposition of Aβ can induce the expression of inflammatory cytokines such as IL-1β, TNF-α, COX-2, and iNOS in RPE cells. Thus, finding a compound that can effectively reduce the inflammatory response may help the treatment of AMD. In this research, we investigated the anti-inflammatory effect of the coral-derived compound 4-(phenylsulfanyl) butan-2-one (4-PSB-2) on Aβ1-42 oligomer (oAβ1-42) added to the human adult retinal pigment epithelial cell line (ARPE-19). Our results demonstrated that 4-PSB-2 can decrease the elevated expressions of TNF-α, COX-2, and iNOS via NF-κB signa...
Additional file 2: The list of specific primers for genotyping (Table S1). The starting point for... more Additional file 2: The list of specific primers for genotyping (Table S1). The starting point for each trial during visible platform test (Table S2). The start positions for each day during hidden platform training trials (Table S3). The details of antibodies and vector used in this study (Table S4). And the sample sizes of the animals for each experiment (Table S5).
Additional file 1: Prdx6−/− mice showed hyperlocomotion in an open field test (Figure S1). Unchan... more Additional file 1: Prdx6−/− mice showed hyperlocomotion in an open field test (Figure S1). Unchanged pro- and mature-BDNF expression in the hippocampus of Prdx6−/− mice (Figure S2). MEK inhibitor, U0126 significantly decreased pERK1/2 in the hippocampus of Prdx6−/− mice (Figure S3). And the expression of PRDX6 in hippocampal astrocytes after contextual testing (Figure S4).
Peroxiredoxin 6 (PRDX6) is a multifunctional enzyme implicated in redox regulation and expressed ... more Peroxiredoxin 6 (PRDX6) is a multifunctional enzyme implicated in redox regulation and expressed in many organs including the brain. It is known to participate in many psychiatric functions, but its role in fear memory is unknown. The present study demonstrates that PRDX6 plays a critical role in the regulation of fear response. Using Prdx6 knockout (Prdx6−/−) mice, we identified that PRDX6 acts as a suppressor in fear memory formation. Lack of Prdx6 leads to the faster fear acquisition and enhanced contextual fear response. This phenomenon was confirmed by the fact that injection of lentivirus-carried human PRDX6-V5 into the hippocampus of Prdx6−/− mice restored the enhanced fear response to the wild-type level. In the hippocampus of Prdx6−/− mice, calcium-dependent PLA2 level was increased, which may compensate for the lack of aiPLA2 function to maintain normal synaptic membranes. On the other hand, reactive oxygen species (ROS) levels did not change, indicating loss of peroxidase...
Alzheimer's disease (AD) is a progressive neurodegenerative disease characterized by cognitiv... more Alzheimer's disease (AD) is a progressive neurodegenerative disease characterized by cognitive deficits. Two hallmarks of AD that cause chronic inflammation and lead to neuronal dysfunction and damage are tau tangles and amyloid plaques. Microglial cells, the primary immune cells of the central nervous system, maintain a homeostatic active/inactive state via a bidirectional, dynamic communication with neurons. Several studies have revealed that dysregulated microglial activation leads to AD pathology. Therefore, we reviewed the relationship between AD and two important signaling complexes, CX3 chemokine ligand 1 (CX3CL1)/CX3CR1 and ATP/P2X7R, that play critical roles in the regulation of microglial activation. CX3CL1/CX3CR1 is one important signaling which controls the microglia function. Altering this pathway can have opposite effects on amyloid and tau pathology in AD. Another important molecule is P2X7R which involves in the activation of microglia. Over activation of P2X7R is evident in AD pathogenesis. In this review, we discuss influence of the two signaling pathways at different stages of AD pathology as well as the drug candidates that can modulate CX3CL1/CX3CR1 and ATP/P2X7R.
Alzheimer's disease (AD) is a neurodegenerative disease characterized by an excessive inflamm... more Alzheimer's disease (AD) is a neurodegenerative disease characterized by an excessive inflammatory response and impaired memory retrieval, including spatial memory, recognition memory, and emotional memory. Acquisition and retrieval of fear memory help one avoid dangers and natural threats. Thus, it is crucial for survival. AD patients with impaired retrieval of fear memory are vulnerable to dangerous conditions. Excessive expression of inflammatory markers is known to impede synaptic transmission and reduce the efficiency of memory retrieval. In wild-type mice, reducing inflammation response can improve fear memory retrieval; however, this effect of this approach is not yet investigated in 3xTg-AD model mice. To date, no satisfactory drug or treatment can attenuate the symptoms of AD despite numerous efforts. In the past few years, the direction of therapeutic drug development for AD has been shifted to natural compounds with anti-inflammatory effect. In the present study, we d...
Background: This research demonstrates that a compound E411, derived from soft coral, may treat d... more Background: This research demonstrates that a compound E411, derived from soft coral, may treat deficit of memory retrieval of triple-transgenic Alzheimer’s disease (3xTg-AD) mice. Alzheimer’s disease (AD) is a neurodegenerative disease and inflammatory brain disorder. The main pathology of AD consists of Ab deposition and intracellular hyperphosphorylated neurofibrillary tangles of tau. The 3xTg-AD mouse is an animal model of AD that exhibits both beta-amyloid and tau pathology mimicking early pathology of human AD. Previous studies have reported that the 3xTg-AD mouse shows impaired spatial and contextual fear memory at 6 months of age. The increased levels of inflammatory cytokines such as TNF-a, COX-2 and iNOS cause memory deficit which lead to synaptic dysfunction, synaptic loss, and neurotoxicity in the brain. However, the effective approach for the prevention or treatment of AD is not yet discovered. E411 is a compound derived from the soft coral. It has been shown to have anti-inflammatory and neuroprotective effects which inhibits iNOS and COX-2 expression in the optic nerve crush model in rats and against the 6-hydroxydopamine-induced neurotoxicity in neuroblastoma SH-SY5Y. This research aims to investigate whether compound E411 can rescue fear memory deficit in 3xTg-AD mice. Methods: Wild type mice (n1⁄45/group) trained with trace fear conditioning (TFC) and treated with/without compound E411. Brain tissues were collected to measure dendritic spine density in the hippocampal region. Then, compound E411 were tested in 6-monthold 3xTg-AD mice (n1⁄48 /group) to investigate their effect in TFC. Brain tissues and proteins were collected to measure the expression of inflammatory markers including TNF-a, COX-2, and iNOS. Results: Wild type mice trained with TFC and treated with/without compound E411 demonstrated that compound E411 increased contextual memory retrieval and dendritic spine density in the hippocampal region. Moreover, compound E411 also significantly increased contextual memory retrieval and enhanced cued memory retrieval when compared to 3xTg-AD untreated group (p 0.05) by suppressing inflammatory markers including TNF-a, COX-2, and iNOS in the hippocampal CA3 region and the basolateral amygdala of 3xTg-AD mice. Conclusions: Our results suggest that compound E411 might act as anti-inflammatory drug that can help reverse memory deficit in AD mice.
Memory retrieval dysfunction is a symptom of schizophrenia, autism spectrum disorder (ASD), and a... more Memory retrieval dysfunction is a symptom of schizophrenia, autism spectrum disorder (ASD), and absence epilepsy (AE), as well as an early sign of Alzheimer's disease. To date, few drugs have been reported to enhance memory retrieval. Here, we found that a coral-derived natural product, excavatolide-B (Exc-B), enhances contextual memory retrieval in both wild-type and mice via repressing the delayed rectifier potassium current, thus lowering the threshold for action potential initiation and enhancing induction of long-term potentiation (LTP). The human gene encodes a T-type calcium channel (Ca3.2), and its mutation is associated with schizophrenia, ASD, and AE, which are all characterized by abnormal memory function. Our previous publication demonstrated that mice exhibit impaired contextual-associated memory retrieval, whilst their retrieval of spatial memory and auditory cued memory remain intact. The effect of Exc-B on enhancing the retrieval of context-associated memory prov...
Various biological effects are associated with radiation exposure. Irradiated cells may elevate t... more Various biological effects are associated with radiation exposure. Irradiated cells may elevate the risk for genetic instability, mutation, and cancer under low levels of radiation exposure, in addition to being able to extend the postradiation side effects in normal tissues. Radiation-induced bystander effect (RIBE) is the focus of rigorous research as it may promote the development of cancer even at low radiation doses. Alterations in the DNA sequence could not explain these biological effects of radiation and it is thought that epigenetics factors may be involved. Indeed, some microRNAs (or miRNAs) have been found to correlate radiation-induced damages and may be potential biomarkers for the various biological effects caused by different levels of radiation exposure. However, the regulatory role that miRNA plays in this aspect remains elusive. In this study, we profiled the expression changes in miRNA under fractionated radiation exposure in human peripheral blood mononuclear cel...
Though damage caused by radiation has been the focus of rigorous research, the mechanisms through... more Though damage caused by radiation has been the focus of rigorous research, the mechanisms through which radiation exerts harmful effects on cells are complex and not well-understood. In particular, the influence of low dose radiation exposure on the regulation of genes and pathways remains unclear. In an attempt to investigate the molecular alterations induced by varying doses of radiation, a genome-wide expression analysis was conducted. Peripheral blood mononuclear cells were collected from five participants and each sample was subjected to 0.5 Gy, 1 Gy, 2.5 Gy, and 5 Gy of cobalt 60 radiation, followed by array-based expression profiling. Gene set enrichment analysis indicated that the immune system and cancer development pathways appeared to be the major affected targets by radiation exposure. Therefore, 1 Gy radioactive exposure seemed to be a critical threshold dosage. In fact, after 1 Gy radiation exposure, expression levels of several genes including FADD, TNFRSF10B, TNFRSF8...
Fear dysregulation is one of the symptoms found in post-traumatic stress disorder (PTSD) patients... more Fear dysregulation is one of the symptoms found in post-traumatic stress disorder (PTSD) patients. The functional abnormality of the hippocampus is known to be implicated in the development of such pathology. Peroxiredoxin 6 (PRDX6) belongs to the peroxiredoxin family. This antioxidant enzyme is expressed throughout the brain, including the hippocampus. Recent evidence reveals that PRDX6 plays an important role in redox regulation and the modulation of several signaling molecules involved in fear regulation. Thus, we hypothesized that PRDX6 plays a role in the regulation of fear memory. We subjected a systemicPrdx6knockout (Prdx6−/−) mice to trace fear conditioning and observed enhanced fear response after training. Intraventricular injection of lentivirus-carried mousePrdx6into the 3rd ventricle reduced the enhanced fear response in these knockout mice. Proteomic analysis followed by validation of western blot analysis revealed that several proteins in the MAPK pathway, such as NTR...
MicroRNA-132 (miR-132) has been demonstrated to affect multiple neuronal functions, including den... more MicroRNA-132 (miR-132) has been demonstrated to affect multiple neuronal functions, including dendritic growth and spinogenesis in cultured neurons and brain slices, as well as learning behavior of animals. However, its role in acquisition of temporal-associated memory remains unclear. In this study, we demonstrated that the mature miR-132 level in mouse hippocampus was significantly increased at 30 min after trace fear conditioning, a type of temporal-associated learning, and returned to baseline values in 2 h. We then knocked down miR-132 expression in vivo by infusing a lentivector expressing anti-miR-132 hairpin RNA into the third ventricle near the anterior hippocampi such RNA diffused laterally to both hippocampal formations, later confirmed by histological analysis. This approach successfully reduced hippocampal miR-132 expression in both naïve and trace fear conditioned groups, and impaired acquisition of trace fear memory in mice. To our knowledge, this result is the first demonstration of change in temporal learning behavior by reducing microRNA (miRNA) level specifically in the hippocampal region.
BackgroundThe relationship between neuronal inflammation and impairment of memory retrieval is no... more BackgroundThe relationship between neuronal inflammation and impairment of memory retrieval is not well established, partially because of the lack of appropriate compound to test this hypothesis. Here we investigated effects of a novel coral‐derived compound on hippocampal inflammation markers and contextual fear memory retrieval using a triple‐transgenic AD (3xTg‐AD) mouse modelMethodThe coral‐derived compound was administered to mice with intraperitoneal injection before subjected to trace fear conditioning. Expression of inflammation markers were measured by western blot analysis or flourescent immunihistochemijcal staining.ResultResults indicate that coral‐derived compound is effective on reducing expression levels of inflammatory markers including TNF‐α, COX‐2, and iNOS in the hippocamapal region, and increased expression of postsynaptic density protein‐95 (PSD‐95) in the hippocampus of 3xTg‐AD mice. It also increased dendritic spine density in hippocampus. Phenotypically, this...
ECa 233 is a standardized extract of Centella asiatica (CA), an herb widely used in traditional C... more ECa 233 is a standardized extract of Centella asiatica (CA), an herb widely used in traditional Chinese and Ayurvedic medicine. Previous studies reported that ECa 233 enhanced memory retention and synaptic plasticity in the hippocampus of healthy rats. Because of this, we became curious whether ECa 233 has a therapeutic effect on the fear memory deficit in the triple transgenic Alzheimer’s disease (3xTg-AD) model mice. Fear memory is a crucial emotional memory for survival that is found to be impaired in patients with early-onset Alzheimer’s disease (AD). In this study, we orally administered ECa 233 (doses: 10, 30, and 100[Formula: see text]mg/kg) to 3xTg-AD mice, who were five months old, for 30 consecutive days. We found that ECa 233 prevented a cued fear memory deficit and enhanced hippocampal long-term potentiation (LTP) in 3xTg-AD mice. Subsequent proteomic and western blot analyses revealed increased expression levels of the molecules related to LTP induction and maintenance,...
Age-related macular degeneration (AMD) is a progressive eye disease that causes irreversible impa... more Age-related macular degeneration (AMD) is a progressive eye disease that causes irreversible impairment of central vision, and effective treatment is not yet available. Extracellular accumulation of amyloid-beta (Aβ) in drusen that lie under the retinal pigment epithelium (RPE) has been reported as one of the early signs of AMD and was found in more than 60% of Alzheimer’s disease (AD) patients. Extracellular deposition of Aβ can induce the expression of inflammatory cytokines such as IL-1β, TNF-α, COX-2, and iNOS in RPE cells. Thus, finding a compound that can effectively reduce the inflammatory response may help the treatment of AMD. In this research, we investigated the anti-inflammatory effect of the coral-derived compound 4-(phenylsulfanyl) butan-2-one (4-PSB-2) on Aβ1-42 oligomer (oAβ1-42) added to the human adult retinal pigment epithelial cell line (ARPE-19). Our results demonstrated that 4-PSB-2 can decrease the elevated expressions of TNF-α, COX-2, and iNOS via NF-κB signa...
Additional file 2: The list of specific primers for genotyping (Table S1). The starting point for... more Additional file 2: The list of specific primers for genotyping (Table S1). The starting point for each trial during visible platform test (Table S2). The start positions for each day during hidden platform training trials (Table S3). The details of antibodies and vector used in this study (Table S4). And the sample sizes of the animals for each experiment (Table S5).
Additional file 1: Prdx6−/− mice showed hyperlocomotion in an open field test (Figure S1). Unchan... more Additional file 1: Prdx6−/− mice showed hyperlocomotion in an open field test (Figure S1). Unchanged pro- and mature-BDNF expression in the hippocampus of Prdx6−/− mice (Figure S2). MEK inhibitor, U0126 significantly decreased pERK1/2 in the hippocampus of Prdx6−/− mice (Figure S3). And the expression of PRDX6 in hippocampal astrocytes after contextual testing (Figure S4).
Peroxiredoxin 6 (PRDX6) is a multifunctional enzyme implicated in redox regulation and expressed ... more Peroxiredoxin 6 (PRDX6) is a multifunctional enzyme implicated in redox regulation and expressed in many organs including the brain. It is known to participate in many psychiatric functions, but its role in fear memory is unknown. The present study demonstrates that PRDX6 plays a critical role in the regulation of fear response. Using Prdx6 knockout (Prdx6−/−) mice, we identified that PRDX6 acts as a suppressor in fear memory formation. Lack of Prdx6 leads to the faster fear acquisition and enhanced contextual fear response. This phenomenon was confirmed by the fact that injection of lentivirus-carried human PRDX6-V5 into the hippocampus of Prdx6−/− mice restored the enhanced fear response to the wild-type level. In the hippocampus of Prdx6−/− mice, calcium-dependent PLA2 level was increased, which may compensate for the lack of aiPLA2 function to maintain normal synaptic membranes. On the other hand, reactive oxygen species (ROS) levels did not change, indicating loss of peroxidase...
Alzheimer's disease (AD) is a progressive neurodegenerative disease characterized by cognitiv... more Alzheimer's disease (AD) is a progressive neurodegenerative disease characterized by cognitive deficits. Two hallmarks of AD that cause chronic inflammation and lead to neuronal dysfunction and damage are tau tangles and amyloid plaques. Microglial cells, the primary immune cells of the central nervous system, maintain a homeostatic active/inactive state via a bidirectional, dynamic communication with neurons. Several studies have revealed that dysregulated microglial activation leads to AD pathology. Therefore, we reviewed the relationship between AD and two important signaling complexes, CX3 chemokine ligand 1 (CX3CL1)/CX3CR1 and ATP/P2X7R, that play critical roles in the regulation of microglial activation. CX3CL1/CX3CR1 is one important signaling which controls the microglia function. Altering this pathway can have opposite effects on amyloid and tau pathology in AD. Another important molecule is P2X7R which involves in the activation of microglia. Over activation of P2X7R is evident in AD pathogenesis. In this review, we discuss influence of the two signaling pathways at different stages of AD pathology as well as the drug candidates that can modulate CX3CL1/CX3CR1 and ATP/P2X7R.
Alzheimer's disease (AD) is a neurodegenerative disease characterized by an excessive inflamm... more Alzheimer's disease (AD) is a neurodegenerative disease characterized by an excessive inflammatory response and impaired memory retrieval, including spatial memory, recognition memory, and emotional memory. Acquisition and retrieval of fear memory help one avoid dangers and natural threats. Thus, it is crucial for survival. AD patients with impaired retrieval of fear memory are vulnerable to dangerous conditions. Excessive expression of inflammatory markers is known to impede synaptic transmission and reduce the efficiency of memory retrieval. In wild-type mice, reducing inflammation response can improve fear memory retrieval; however, this effect of this approach is not yet investigated in 3xTg-AD model mice. To date, no satisfactory drug or treatment can attenuate the symptoms of AD despite numerous efforts. In the past few years, the direction of therapeutic drug development for AD has been shifted to natural compounds with anti-inflammatory effect. In the present study, we d...
Background: This research demonstrates that a compound E411, derived from soft coral, may treat d... more Background: This research demonstrates that a compound E411, derived from soft coral, may treat deficit of memory retrieval of triple-transgenic Alzheimer’s disease (3xTg-AD) mice. Alzheimer’s disease (AD) is a neurodegenerative disease and inflammatory brain disorder. The main pathology of AD consists of Ab deposition and intracellular hyperphosphorylated neurofibrillary tangles of tau. The 3xTg-AD mouse is an animal model of AD that exhibits both beta-amyloid and tau pathology mimicking early pathology of human AD. Previous studies have reported that the 3xTg-AD mouse shows impaired spatial and contextual fear memory at 6 months of age. The increased levels of inflammatory cytokines such as TNF-a, COX-2 and iNOS cause memory deficit which lead to synaptic dysfunction, synaptic loss, and neurotoxicity in the brain. However, the effective approach for the prevention or treatment of AD is not yet discovered. E411 is a compound derived from the soft coral. It has been shown to have anti-inflammatory and neuroprotective effects which inhibits iNOS and COX-2 expression in the optic nerve crush model in rats and against the 6-hydroxydopamine-induced neurotoxicity in neuroblastoma SH-SY5Y. This research aims to investigate whether compound E411 can rescue fear memory deficit in 3xTg-AD mice. Methods: Wild type mice (n1⁄45/group) trained with trace fear conditioning (TFC) and treated with/without compound E411. Brain tissues were collected to measure dendritic spine density in the hippocampal region. Then, compound E411 were tested in 6-monthold 3xTg-AD mice (n1⁄48 /group) to investigate their effect in TFC. Brain tissues and proteins were collected to measure the expression of inflammatory markers including TNF-a, COX-2, and iNOS. Results: Wild type mice trained with TFC and treated with/without compound E411 demonstrated that compound E411 increased contextual memory retrieval and dendritic spine density in the hippocampal region. Moreover, compound E411 also significantly increased contextual memory retrieval and enhanced cued memory retrieval when compared to 3xTg-AD untreated group (p 0.05) by suppressing inflammatory markers including TNF-a, COX-2, and iNOS in the hippocampal CA3 region and the basolateral amygdala of 3xTg-AD mice. Conclusions: Our results suggest that compound E411 might act as anti-inflammatory drug that can help reverse memory deficit in AD mice.
Memory retrieval dysfunction is a symptom of schizophrenia, autism spectrum disorder (ASD), and a... more Memory retrieval dysfunction is a symptom of schizophrenia, autism spectrum disorder (ASD), and absence epilepsy (AE), as well as an early sign of Alzheimer's disease. To date, few drugs have been reported to enhance memory retrieval. Here, we found that a coral-derived natural product, excavatolide-B (Exc-B), enhances contextual memory retrieval in both wild-type and mice via repressing the delayed rectifier potassium current, thus lowering the threshold for action potential initiation and enhancing induction of long-term potentiation (LTP). The human gene encodes a T-type calcium channel (Ca3.2), and its mutation is associated with schizophrenia, ASD, and AE, which are all characterized by abnormal memory function. Our previous publication demonstrated that mice exhibit impaired contextual-associated memory retrieval, whilst their retrieval of spatial memory and auditory cued memory remain intact. The effect of Exc-B on enhancing the retrieval of context-associated memory prov...
Various biological effects are associated with radiation exposure. Irradiated cells may elevate t... more Various biological effects are associated with radiation exposure. Irradiated cells may elevate the risk for genetic instability, mutation, and cancer under low levels of radiation exposure, in addition to being able to extend the postradiation side effects in normal tissues. Radiation-induced bystander effect (RIBE) is the focus of rigorous research as it may promote the development of cancer even at low radiation doses. Alterations in the DNA sequence could not explain these biological effects of radiation and it is thought that epigenetics factors may be involved. Indeed, some microRNAs (or miRNAs) have been found to correlate radiation-induced damages and may be potential biomarkers for the various biological effects caused by different levels of radiation exposure. However, the regulatory role that miRNA plays in this aspect remains elusive. In this study, we profiled the expression changes in miRNA under fractionated radiation exposure in human peripheral blood mononuclear cel...
Though damage caused by radiation has been the focus of rigorous research, the mechanisms through... more Though damage caused by radiation has been the focus of rigorous research, the mechanisms through which radiation exerts harmful effects on cells are complex and not well-understood. In particular, the influence of low dose radiation exposure on the regulation of genes and pathways remains unclear. In an attempt to investigate the molecular alterations induced by varying doses of radiation, a genome-wide expression analysis was conducted. Peripheral blood mononuclear cells were collected from five participants and each sample was subjected to 0.5 Gy, 1 Gy, 2.5 Gy, and 5 Gy of cobalt 60 radiation, followed by array-based expression profiling. Gene set enrichment analysis indicated that the immune system and cancer development pathways appeared to be the major affected targets by radiation exposure. Therefore, 1 Gy radioactive exposure seemed to be a critical threshold dosage. In fact, after 1 Gy radiation exposure, expression levels of several genes including FADD, TNFRSF10B, TNFRSF8...
Fear dysregulation is one of the symptoms found in post-traumatic stress disorder (PTSD) patients... more Fear dysregulation is one of the symptoms found in post-traumatic stress disorder (PTSD) patients. The functional abnormality of the hippocampus is known to be implicated in the development of such pathology. Peroxiredoxin 6 (PRDX6) belongs to the peroxiredoxin family. This antioxidant enzyme is expressed throughout the brain, including the hippocampus. Recent evidence reveals that PRDX6 plays an important role in redox regulation and the modulation of several signaling molecules involved in fear regulation. Thus, we hypothesized that PRDX6 plays a role in the regulation of fear memory. We subjected a systemicPrdx6knockout (Prdx6−/−) mice to trace fear conditioning and observed enhanced fear response after training. Intraventricular injection of lentivirus-carried mousePrdx6into the 3rd ventricle reduced the enhanced fear response in these knockout mice. Proteomic analysis followed by validation of western blot analysis revealed that several proteins in the MAPK pathway, such as NTR...
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