scholarly journals Chronic Phencyclidine Increases Synapsin-1 and Synaptic Adaptation Proteins in the Medial Prefrontal Cortex

2013 ◽  
Vol 2013 ◽  
pp. 1-8 ◽  
Author(s):  
Chris Pickering ◽  
Mia Ericson ◽  
Bo Söderpalm
Keyword(s):  
Prefrontal Cortex ◽  
Medial Prefrontal Cortex ◽  
Protein Identification ◽  
Underlying Mechanism ◽  
Proteomics Analysis ◽  
2D Dige ◽  
Y Maze ◽  
Male Wistar Rats ◽  
Schizophrenic Patients ◽  
Synapsin 1

Phencyclidine (PCP) mimics many aspects of schizophrenia, yet the underlying mechanism of neurochemical adaptation for PCP is unknown. We therefore used proteomics to study changes in the medial prefrontal cortex in animals with PCP-induced behavioural deficits. Male Wistar rats were injected with saline or 5 mg/kg phencyclidine for 5 days followed by two days of washout. Spontaneous alternation behaviour was tested in a Y-maze and then proteins were extracted from the medial prefrontal cortex. 2D-DIGE analysis followed by spot picking and protein identification with mass spectrometry then provided a list of differentially expressed proteins. Treatment with 5 mg/kg phencyclidine decreased the percentage of correct alternations in the Y-maze compared to saline-treated controls. Proteomics analysis of the medial prefrontal cortex found upregulation of 6 proteins (synapsin-1, Dpysl3, Aco2, Fscn1, Tuba1c, and Mapk1) and downregulation of 11 (Bin1, Dpysl2, Sugt1, ApoE, Psme1, ERp29, Pgam1, Uchl1, Ndufv2, Pcmt1, and Vdac1). A trend to upregulation was observed for Gnb4 and Capza2, while downregulation trends were noted for alpha-enolase and Fh. Many of the hits in this study concur with recent postmortem data from schizophrenic patients and this further validates the use of phencyclidine in preclinical translational research.

scholarly journals Change in the plasma proteome associated with canine cognitive dysfunction syndrome (CCDS) in Thailand

2021 ◽  
Vol 17 (1) ◽  
Author(s):  
Sataporn Phochantachinda ◽  
Boonrat Chantong ◽  
Onrapak Reamtong ◽  
Duangthip Chatchaisak
Keyword(s):  
Cognitive Dysfunction ◽  
Plasma Proteins ◽  
Protein Identification ◽  
Rating Scale ◽  
Neurodegenerative Disorder ◽  
Underlying Mechanism ◽  
Population Based ◽  
Diagnostic Biomarker ◽  
Adult Group ◽  
Proteomics Analysis

Abstract Background Canine cognitive dysfunction syndrome (CCDS) is a progressive neurodegenerative disorder found in senior dogs. Due to the lack of biological markers, CCDS is commonly underdiagnosed. The aim of this study was to identify potential plasma biomarkers using proteomics techniques and to increase our understanding of the pathogenic mechanism of the disease. Plasma amyloid beta 42 (Aβ42) has been seen to be a controversial biomarker for CCDS. Proteomics analysis was performed for protein identification and quantification. Results Within CCDS, ageing, and adult dogs, 87 proteins were identified specific to Canis spp. in the plasma samples. Of 87 proteins, 48 and 41 proteins were changed in the ageing and adult groups, respectively. Several distinctly expressed plasma proteins identified in CCDS were involved in complement and coagulation cascades and the apolipoprotein metabolism pathway. Plasma Aβ42 levels considerably overlapped within the CCDS and ageing groups. In the adult group, the Aβ42 level was low compared with that in the other groups. Nevertheless, plasma Aβ42 did not show a correlation with the Canine Cognitive Dysfunction Rating scale (CCDR) score in the CCDS group (p = 0.131, R2 = 0.261). Conclusions Our present findings suggest that plasma Aβ42 does not show potential for use as a diagnostic biomarker in CCDS. The nano-LC-MS/MS data revealed that the predictive underlying mechanism of CCDS was the co-occurrence of inflammation-mediated acute phase response proteins and complement and coagulation cascades that partly functioned by apolipoproteins and lipid metabolism. Some of the differentially expressed proteins may serve as potential predictor biomarkers along with Aβ42 in plasma for improved CCDS diagnosis. Further study in larger population-based cohort study is required in validation to define the correlation between protein expression and the pathogenesis of CCDS.

scholarly journals Layer- and subregion-specific differences in the neurophysiological properties of rat medial prefrontal cortex pyramidal neurons

2018 ◽  
Vol 119 (1) ◽  
pp. 177-191 ◽  
Author(s):  
Chenghui Song ◽  
James R. Moyer
Keyword(s):  
Prefrontal Cortex ◽  
Medial Prefrontal Cortex ◽  
Pyramidal Neurons ◽  
Conditioned Fear ◽  
Input Resistance ◽  
Underlying Mechanism ◽  
Fear Memory ◽  
Membrane Properties ◽  
Spike Threshold ◽  
Memory Acquisition

Medial prefrontal cortex (mPFC) is critical for the expression of long-term conditioned fear. However, the neural circuits involving fear memory acquisition and retrieval are still unclear. Two subregions within mPFC that have received a lot of attention are the prelimbic (PL) and infralimbic (IL) cortices (e.g., Santini E, Quirk GJ, Porter JT. J Neurosci 28: 4028–4036, 2008; Song C, Ehlers VL, Moyer JR Jr. J Neurosci 35: 13511–13524, 2015). Interestingly, PL and IL may play distinct roles during fear memory acquisition and retrieval but the underlying mechanism is poorly understood. One possibility is that the intrinsic membrane properties differ between these subregions. Thus, the current study was carried out to characterize the basic membrane properties of mPFC neurons in different layers and subregions. We found that pyramidal neurons in L2/3 were more hyperpolarized and less excitable than in L5. This was observed in both IL and PL and was associated with an enhanced h-current in L5 neurons. Within L2/3, IL neurons were more excitable than those in PL, which may be due to a lower spike threshold and higher input resistance in IL neurons. Within L5, the intrinsic excitability was comparable between neurons obtained in IL and PL. Thus, the heterogeneity in physiological properties of mPFC neurons may underlie the observed subregion-specific contribution of mPFC in cognitive function and emotional control, such as fear memory expression. NEW & NOTEWORTHY This is the first study to demonstrate that medial prefrontal cortical (mPFC) neurons are heterogeneous in both a layer- and a subregion-specific manner. Specifically, L5 neurons are more depolarized and more excitable than those neurons in L2/3, which is likely due to variations in h-current. Also, infralimbic neurons are more excitable than those of prelimbic neurons in layer 2/3, which may be due to differences in certain intrinsic properties, including input resistance and spike threshold.

scholarly journals Change in the plasma proteome associated with canine cognitive dysfunction syndrome (CCDS) in Thailand

2021 ◽  
Author(s):  
Sataporn Phochantachinda ◽  
Boonrat Chantong ◽  
Onrapak Reamtong ◽  
Duangthip Chatchaisak
Keyword(s):  
Cognitive Dysfunction ◽  
Plasma Proteins ◽  
Protein Identification ◽  
Rating Scale ◽  
Neurodegenerative Disorder ◽  
Underlying Mechanism ◽  
Population Based ◽  
Diagnostic Biomarker ◽  
Adult Group ◽  
Proteomics Analysis

Abstract Background: Canine cognitive dysfunction syndrome (CCDS) is a progressive neurodegenerative disorder found in senior dogs. Due to the lack of biological markers, CCDS is commonly underdiagnosed. The aim of this study was to identify potential plasma biomarkers using proteomics techniques and to increase our understanding of the pathogenic mechanism of the disease. Plasma amyloid beta 42 (Aβ42) has been seen to be a controversial biomarker for CCDS. Proteomics analysis was performed for protein identification and quantification.Results: Within CCDS, ageing, and adult dogs, 87 proteins were identified specific to Canis spp. in the plasma samples. Of 87 proteins, 48 and 41 proteins were changed in the ageing and adult groups, Several distinctly expressed plasma proteins identified in CCDS were involved in complement and coagulation cascades and the apolipoprotein metabolism pathway. Plasma Aβ42 levels considerably overlapped within the CCDS and ageing groups. In the adult group, the Aβ42 level was low compared with that in the other groups. Nevertheless, plasma Aβ42 did not show a correlation with the Canine Cognitive Dysfunction Rating scale (CCDR) score in the CCDS group (p=0.131, R2=0.261).Conclusions: Our present findings suggest that plasma Aβ42 does not show potential for use as a diagnostic biomarker in CCDS. The nano-LC-MS/MS data revealed that the predictive underlying mechanism of CCDS was the co-occurrence of inflammation-mediated acute phase response proteins and complement and coagulation cascades that partly functioned by apolipoproteins and lipid metabolism. Some of the differentially expressed proteins may serve as potential predictor biomarkers along with Aβ42 in plasma for improved CCDS diagnosis. Further study in larger population-based cohort study is required in validation to define the correlation between protein expression and the pathogenesis of CCDS.

erbb4 Deficits in Chandelier Cells of the Medial Prefrontal Cortex Confer Cognitive Dysfunctions: Implications for Schizophrenia

2018 ◽  
Vol 29 (10) ◽  
pp. 4334-4346 ◽  
Author(s):  
Jian-Ming Yang ◽  
Chen-Jie Shen ◽  
Xiao-Juan Chen ◽  
Ying Kong ◽  
Yi-Si Liu ◽  
...  
Keyword(s):  
Prefrontal Cortex ◽  
Medial Prefrontal Cortex ◽  
Pyramidal Neuron ◽  
Initial Segment ◽  
Susceptibility Gene ◽  
Gabaergic Interneuron ◽  
Cognitive Dysfunctions ◽  
Axonal Initial Segment ◽  
Schizophrenic Patients ◽  
Chandelier Cells

Abstract erbb4 is a known susceptibility gene for schizophrenia. Chandelier cells (ChCs, also known as axo-axonic cells) are a distinct GABAergic interneuron subtype that exclusively target the axonal initial segment, which is the site of pyramidal neuron action potential initiation. ChCs are a source of ErbB4 expression and alterations in ChC-pyramidal neuron connectivity occur in the medial prefrontal cortex (mPFC) of schizophrenic patients and animal models of schizophrenia. However, the contribution of ErbB4 in mPFC ChCs to the pathogenesis of schizophrenia remains unknown. By conditional deletion or knockdown of ErbB4 from mPFC ChCs, we demonstrated that ErbB4 deficits led to impaired ChC-pyramidal neuron connections and cognitive dysfunctions. Furthermore, the cognitive dysfunctions were normalized by L-838417, an agonist of GABAAα2 receptors enriched in the axonal initial segment. Given that cognitive dysfunctions are a core symptom of schizophrenia, our results may provide a new perspective for understanding the etiology of schizophrenia and suggest that GABAAα2 receptors may be potential pharmacological targets for its treatment.

scholarly journals The Plasma Amyloid Beta 42 (Aβ42) and Proteomics Profile Related to Canine Cognitive Dysfunction Syndrome (CCDS) in Thailand

2020 ◽  
Author(s):  
Sataporn Phochantachinda ◽  
Boonrat Chantong ◽  
Onrapak Reamtong ◽  
Duangthip Chatchaisak
Keyword(s):  
Cognitive Dysfunction ◽  
Amyloid Beta ◽  
Plasma Proteins ◽  
Protein Identification ◽  
Rating Scale ◽  
Neurodegenerative Disorder ◽  
Underlying Mechanism ◽  
Adult Group ◽  
Proteomics Analysis ◽  
Amyloid Beta 42

Abstract Background: Canine cognitive dysfunction syndrome (CCDS) is a progressive neurodegenerative disorder found in senior dogs. Due to the lack of biological markers, CCDS is commonly underdiagnosed. The aim of this study was to identify potential plasma biomarkers using proteomics techniques and to increase our understanding of the pathogenic mechanism of the disease. Plasma amyloid beta 42 (Aβ42) has been seen to be a controversial biomarker for CCDS. Proteomics analysis was performed for protein identification and quantification.Results: Within CCDS, ageing, and adult dogs, 87 proteins were identified specific to Canis spp. in the plasma samples. Of 87 proteins, 45 and 52 proteins were changed in the ageing and adult groups, respectively. Several distinctly expressed plasma proteins identified in CCDS were involved in complement and coagulation cascades and the apolipoprotein metabolism pathway. Plasma Aβ42 levels considerably overlapped within the CCDS and ageing groups. In the adult group, the Aβ42 level was low compared with that in the other groups. Nevertheless, plasma Aβ42 did not show a correlation with the Canine Cognitive Dysfunction Rating scale (CCDR) score in the CCDS group (p = 0.125, R2 = 0.27).Conclusions: Our present findings suggest that plasma Aβ42 does not show potential for use as a diagnostic biomarker in CCDS. The nano-LC-MS/MS data revealed that the predictive underlying mechanism of CCDS was the co-occurrence of inflammation-mediated acute phase response proteins and complement and coagulation cascades that partly functioned by apolipoproteins and lipid metabolism. Some of the differentially expressed proteins may serve as potential predictor biomarkers along with Aβ42 in plasma for improved CCDS diagnosis.

scholarly journals Neurocognitive and Neuroarchitectural Changes in the Prefrontal Cortex of Wistar Rats Treated with Highly Active Antiretroviral Therapy

2021 ◽  
Vol 12 (2) ◽  
pp. 67-75
Author(s):  
Olufunke Dosumu ◽  
◽  
Edidiong Akang ◽  
Edem Edem ◽  
Samuel Afolayan ◽  
...  
Keyword(s):  
Prefrontal Cortex ◽  
Antiretroviral Therapy ◽  
Highly Active Antiretroviral Therapy ◽  
Wistar Rats ◽  
Pyramidal Cells ◽  
Control Group ◽  
Highly Active ◽  
Y Maze ◽  
Male Wistar Rats ◽  
The Right

The use of highly active antiretroviral therapy has proven to be highly effective in the treatment of human immunodeficiency virus 1 (HIV-1) infection. However, its impact on cognition has not been fully explored. This study was designed to assess the impacts of antiretroviral therapy on cognitive function and histoarchitecture of the prefrontal cortex of Wistar rats. Forty adult male Wistar rats weighing 180-200 g were randomly assigned to 4 groups: control, tenofovir, lamivudine and efavirenz (n=10), which received 1 ml distilled water and 6 mg/kg, 6 mg/kg and 12 mg/kg, respectively. Spatial memory scores were assessed using the Y-maze test. Following behavioural studies, the animals were euthanized, and their whole brains harvested. The prefrontal cortex was sectioned and processed for oxidative stress, histological and immunohistochemical analyses. There was a significant decrease in percentage alternation evaluated from the right/wrong decisions scored from the tenofovir and lamivudine groups, compared to the control group (p<0.05). malondialdehyde (MDA) and reduced glutathione (GSH) levels were elevated following lamivudine and tenofovir exposure in the rats’ prefrontal cortices, respectively, compared to control (p<0.05). There were also significant alterations of cortical pyramidal cells in the tenofovir and lamivudine groups. Additionally, marked astrogliosis with increased glial fibrillary acidic protein expression was observed, consistent with the structural alterations, especially in the lamivudine group. Our findings suggest that, of the three highly active antiretroviral therapy (HAART) drugs studied, lamivudine may be a major culprit in the progressive neurological damage and cognitive impairment in HIV-infected individuals on HAART.

scholarly journals Change in the plasma proteome associated with canine cognitive dysfunction syndrome (CCDS) in Thailand

2020 ◽  
Author(s):  
Sataporn Phochantachinda ◽  
Boonrat Chantong ◽  
Onrapak Reamtong ◽  
Duangthip Chatchaisak
Keyword(s):  
Cognitive Dysfunction ◽  
Plasma Proteins ◽  
Protein Identification ◽  
Rating Scale ◽  
Neurodegenerative Disorder ◽  
Underlying Mechanism ◽  
Diagnostic Biomarker ◽  
Adult Group ◽  
Proteomics Analysis ◽  
Metabolism Pathway

Abstract Background: Canine cognitive dysfunction syndrome (CCDS) is a progressive neurodegenerative disorder found in senior dogs. Due to the lack of biological markers, CCDS is commonly underdiagnosed. The aim of this study was to identify potential plasma biomarkers using proteomics techniques and to increase our understanding of the pathogenic mechanism of the disease. Plasma amyloid beta 42 (Aβ42) has been seen to be a controversial biomarker for CCDS. Proteomics analysis was performed for protein identification and quantification. Results: Within CCDS, ageing, and adult dogs, 87 proteins were identified specific to Canis spp. in the plasma samples. Of 87 proteins, 48 and 41 proteins were changed in the ageing and adult groups, respectively. Several distinctly expressed plasma proteins identified in CCDS were involved in complement and coagulation cascades and the apolipoprotein metabolism pathway. Plasma Aβ42 levels considerably overlapped within the CCDS and ageing groups. In the adult group, the Aβ42 level was low compared with that in the other groups. Nevertheless, plasma Aβ42 did not show a correlation with the Canine Cognitive Dysfunction Rating scale (CCDR) score in the CCDS group (p=0.131, R2=0.261).Conclusions: Our present findings suggest that plasma Aβ42 does not show potential for use as a diagnostic biomarker in CCDS. The nano-LC-MS/MS data revealed that the predictive underlying mechanism of CCDS was the co-occurrence of inflammation-mediated acute phase response proteins and complement and coagulation cascades that partly functioned by apolipoproteins and lipid metabolism. Some of the differentially expressed proteins may serve as potential predictor biomarkers along with Aβ42 in plasma for improved CCDS diagnosis.

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