The aim of this study was to examine the association of factor V Leiden, prothrombin and methylen... more The aim of this study was to examine the association of factor V Leiden, prothrombin and methylenetetrahydrofolate reductase (MTHFR) polymorphisms and preeclampsia (PE) in Southeast of Iran. This case-control study was performed on 192 preeclamptic and 196 normotensive pregnant women. Single nucleotide polymorphisms were genotyped using polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) and Tetra ARMS methods. No significant differences were observed in distribution of MTHFR C677T and FVL polymorphisms between two groups. There was a significant difference in frequency of 1298AC genotype in PE pregnant women compared to controls (P = 0.03). No 20210A allele of prothrombin gene was observed in this population. The analysis of MTHFR and factor V Leiden polymorphisms between early-onset PE (EOPE) and late-onset PE (LOPE) showed significant differences in MTHFR A1298C polymorphism (AC and CC vs AA, P = 0.012 and P = 0.006, respectively) and G1691A polymorphism of FVL(GA vs GG, P = 0.03). Moreover, the analysis of three SNPs between EOPE and controls showed significant differences in MTHFR C677T (CT + TT vs CC, P = 0.035) and MTHFR A1298C (AC and CC vs AA, P = 0.001 and P = 0.006, respectively) polymorphisms. The synergic effect of MTHFR A1298C and C677T polymorphisms showed increased risk of EOPE. MTHFR A1298C polymorphism was associated with PE. Although MTHFR C677T and FVL polymorphisms did not differ between PE patients and controls, significant differences in MTHFR A1298C, C677T and FVL polymorphisms between EOPE and LOPE/controls were observed. The synergic effect of MTHFR variants could increase PE and EOPE risk.
Stimulus-driven responses in the cortex reduce due to prior exposure to sensory stimuli, a phenom... more Stimulus-driven responses in the cortex reduce due to prior exposure to sensory stimuli, a phenomenon called sensory adaptation. Depression of synaptic supplies and afterhyperpolarization (AHP) following each action potential are the main proposed mechanisms for adaptation. In vitro studies have shown that the neuronal adaptation in the barrel cortex depends on slow AHPs. Such AHPs can be affected by neuromodulators, such as noradrenaline. This evidence suggests that Locus Coeruleus (LC) noradrenergic system may reduce sensory adaptation through this cellular mechanism. We proposed that LC stimulation before whisker deflection can affect the degree of adaptation in the barrel cortex, depending on the nature of noradrenergic interactions in the barrel cortex. We coupled adapted or non-adapted whisker deflections with LC phasic stimulation with a 400 ms interval. A 50ms sinusoidal vibration was applied to the whisker immediately before the test deflection. Neuronal activity was record...
Locus Coeruleus (LC) noradrenergic system has widespread projections throughout the brain and aff... more Locus Coeruleus (LC) noradrenergic system has widespread projections throughout the brain and affects sensory processing in various modalities. Inhibition of both spontaneous and sensory-evoked cortical activity is well-documented in early experiments by either LC electrical micro-stimulation or local application of norepinephrine (NE). However, the temporal profile of LC modulation of sensory response is not well-established. Here, we recorded neuronal activity from the rat barrel cortex under urethane anesthesia and coupled LC micro-stimulation with brief mechanical deflection of whiskers at 10 different time lags (50-500 ms). LC micro-stimulation exhibited a biphasic effect on BC spontaneous activity: a period of suppression (∼100 ms) followed by a period of excitation (∼200 ms). This profile was highly consistent across BC units: 82% of BC units showed early suppression and 91% of BC units showed late excitation. We observed a similar effect on the sensory-evoked response: at 50...
The aim of this study was to examine the association of factor V Leiden, prothrombin and methylen... more The aim of this study was to examine the association of factor V Leiden, prothrombin and methylenetetrahydrofolate reductase (MTHFR) polymorphisms and preeclampsia (PE) in Southeast of Iran. This case-control study was performed on 192 preeclamptic and 196 normotensive pregnant women. Single nucleotide polymorphisms were genotyped using polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) and Tetra ARMS methods. No significant differences were observed in distribution of MTHFR C677T and FVL polymorphisms between two groups. There was a significant difference in frequency of 1298AC genotype in PE pregnant women compared to controls (P = 0.03). No 20210A allele of prothrombin gene was observed in this population. The analysis of MTHFR and factor V Leiden polymorphisms between early-onset PE (EOPE) and late-onset PE (LOPE) showed significant differences in MTHFR A1298C polymorphism (AC and CC vs AA, P = 0.012 and P = 0.006, respectively) and G1691A polymorphism...
Cortical state modulates the background activity of cortical neurons, and their evoked response t... more Cortical state modulates the background activity of cortical neurons, and their evoked response to sensory stimulation. Multiple mechanisms are involved in switching between cortical states including various neuromodulatory systems. Locus Coeruleus (LC) is one of the major neuromodulatory nuclei in the brainstem with widespread projections throughout the brain and modulates the activity of cells and networks. Here, we quantified the link between the LC spontaneous activity, cortical state and sensory processing in the rat vibrissal somatosensory "barrel" cortex (BC). We simultaneously recorded unit activity from LC and BC along with prefrontal electroencephalogram (EEG) while presenting brief whisker deflections under urethane anesthesia. The ratio of low to high frequency components of EEG (referred to as the L/H ratio) was employed to identify cortical state. We found that the spontaneous activity of LC units exhibited a negative correlation with the L/H ratio. Cross-correlation analysis revealed that changes in LC firing preceded changes in the cortical state: the correlation of the LC firing profile with the L/H ratio was maximal at an average lag of -1.2 s. We further quantified BC neuronal responses to whisker stimulation during the synchronized and desynchronized states. In the desynchronized state, BC neurons showed lower stimulus detection threshold, higher response fidelity, and shorter response latency. The most prominent change was observed in the late phase of BC evoked activity (100-400 ms post stimulus onset): almost every BC unit exhibited a greater late response during the desynchronized state. Categorization of the BC evoked responses based on LC activity (into high and low LC discharge rates) resulted in highly similar response profiles compared to categorization based on the cortical state (low and high L/H ratios). These findings provide evidence for the involvement of the LC neuromodulatory system in desynchronization of cortical state and the consequent enhancement of sensory coding efficiency.
The results of mutation screening of 24 exons of LRRK2 in 60 Iranian Parkinson&am... more The results of mutation screening of 24 exons of LRRK2 in 60 Iranian Parkinson's Disease patients are presented. The Iranian cohort represents a novel population and was notably young (average age at onset of disease: 36.0 years). Fifty sequence variations were found, seventeen of which are novel. Variations considered possibly associated with disease were screened in available family members, 145 additional patients and 220 control individuals. It was surmised that four novel sequence variations (IVS49+178A>G, p.R1725Q, p.Q1823K, and p.D2175H) may be associated with PD status, albeit they may be very rare non-disease associated variations. The four variations were all observed in the heterozygous state in early onset cases. If one or more of the variations do indeed contribute to disease status, their penetrance is expected to be low.
The results of mutation screening of 24 exons of LRRK2 in 60 Iranian Parkinson&am... more The results of mutation screening of 24 exons of LRRK2 in 60 Iranian Parkinson's Disease patients are presented. The Iranian cohort represents a novel population and was notably young (average age at onset of disease: 36.0 years). Fifty sequence variations were found, seventeen of which are novel. Variations considered possibly associated with disease were screened in available family members, 145 additional patients and 220 control individuals. It was surmised that four novel sequence variations (IVS49+178A>G, p.R1725Q, p.Q1823K, and p.D2175H) may be associated with PD status, albeit they may be very rare non-disease associated variations. The four variations were all observed in the heterozygous state in early onset cases. If one or more of the variations do indeed contribute to disease status, their penetrance is expected to be low.
The aim of this study was to examine the association of factor V Leiden, prothrombin and methylen... more The aim of this study was to examine the association of factor V Leiden, prothrombin and methylenetetrahydrofolate reductase (MTHFR) polymorphisms and preeclampsia (PE) in Southeast of Iran. This case-control study was performed on 192 preeclamptic and 196 normotensive pregnant women. Single nucleotide polymorphisms were genotyped using polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) and Tetra ARMS methods. No significant differences were observed in distribution of MTHFR C677T and FVL polymorphisms between two groups. There was a significant difference in frequency of 1298AC genotype in PE pregnant women compared to controls (P = 0.03). No 20210A allele of prothrombin gene was observed in this population. The analysis of MTHFR and factor V Leiden polymorphisms between early-onset PE (EOPE) and late-onset PE (LOPE) showed significant differences in MTHFR A1298C polymorphism (AC and CC vs AA, P = 0.012 and P = 0.006, respectively) and G1691A polymorphism of FVL(GA vs GG, P = 0.03). Moreover, the analysis of three SNPs between EOPE and controls showed significant differences in MTHFR C677T (CT + TT vs CC, P = 0.035) and MTHFR A1298C (AC and CC vs AA, P = 0.001 and P = 0.006, respectively) polymorphisms. The synergic effect of MTHFR A1298C and C677T polymorphisms showed increased risk of EOPE. MTHFR A1298C polymorphism was associated with PE. Although MTHFR C677T and FVL polymorphisms did not differ between PE patients and controls, significant differences in MTHFR A1298C, C677T and FVL polymorphisms between EOPE and LOPE/controls were observed. The synergic effect of MTHFR variants could increase PE and EOPE risk.
The aim of this study was to examine the association of factor V Leiden, prothrombin and methylen... more The aim of this study was to examine the association of factor V Leiden, prothrombin and methylenetetrahydrofolate reductase (MTHFR) polymorphisms and preeclampsia (PE) in Southeast of Iran. This case-control study was performed on 192 preeclamptic and 196 normotensive pregnant women. Single nucleotide polymorphisms were genotyped using polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) and Tetra ARMS methods. No significant differences were observed in distribution of MTHFR C677T and FVL polymorphisms between two groups. There was a significant difference in frequency of 1298AC genotype in PE pregnant women compared to controls (P = 0.03). No 20210A allele of prothrombin gene was observed in this population. The analysis of MTHFR and factor V Leiden polymorphisms between early-onset PE (EOPE) and late-onset PE (LOPE) showed significant differences in MTHFR A1298C polymorphism (AC and CC vs AA, P = 0.012 and P = 0.006, respectively) and G1691A polymorphism of FVL(GA vs GG, P = 0.03). Moreover, the analysis of three SNPs between EOPE and controls showed significant differences in MTHFR C677T (CT + TT vs CC, P = 0.035) and MTHFR A1298C (AC and CC vs AA, P = 0.001 and P = 0.006, respectively) polymorphisms. The synergic effect of MTHFR A1298C and C677T polymorphisms showed increased risk of EOPE. MTHFR A1298C polymorphism was associated with PE. Although MTHFR C677T and FVL polymorphisms did not differ between PE patients and controls, significant differences in MTHFR A1298C, C677T and FVL polymorphisms between EOPE and LOPE/controls were observed. The synergic effect of MTHFR variants could increase PE and EOPE risk.
Stimulus-driven responses in the cortex reduce due to prior exposure to sensory stimuli, a phenom... more Stimulus-driven responses in the cortex reduce due to prior exposure to sensory stimuli, a phenomenon called sensory adaptation. Depression of synaptic supplies and afterhyperpolarization (AHP) following each action potential are the main proposed mechanisms for adaptation. In vitro studies have shown that the neuronal adaptation in the barrel cortex depends on slow AHPs. Such AHPs can be affected by neuromodulators, such as noradrenaline. This evidence suggests that Locus Coeruleus (LC) noradrenergic system may reduce sensory adaptation through this cellular mechanism. We proposed that LC stimulation before whisker deflection can affect the degree of adaptation in the barrel cortex, depending on the nature of noradrenergic interactions in the barrel cortex. We coupled adapted or non-adapted whisker deflections with LC phasic stimulation with a 400 ms interval. A 50ms sinusoidal vibration was applied to the whisker immediately before the test deflection. Neuronal activity was record...
Locus Coeruleus (LC) noradrenergic system has widespread projections throughout the brain and aff... more Locus Coeruleus (LC) noradrenergic system has widespread projections throughout the brain and affects sensory processing in various modalities. Inhibition of both spontaneous and sensory-evoked cortical activity is well-documented in early experiments by either LC electrical micro-stimulation or local application of norepinephrine (NE). However, the temporal profile of LC modulation of sensory response is not well-established. Here, we recorded neuronal activity from the rat barrel cortex under urethane anesthesia and coupled LC micro-stimulation with brief mechanical deflection of whiskers at 10 different time lags (50-500 ms). LC micro-stimulation exhibited a biphasic effect on BC spontaneous activity: a period of suppression (∼100 ms) followed by a period of excitation (∼200 ms). This profile was highly consistent across BC units: 82% of BC units showed early suppression and 91% of BC units showed late excitation. We observed a similar effect on the sensory-evoked response: at 50...
The aim of this study was to examine the association of factor V Leiden, prothrombin and methylen... more The aim of this study was to examine the association of factor V Leiden, prothrombin and methylenetetrahydrofolate reductase (MTHFR) polymorphisms and preeclampsia (PE) in Southeast of Iran. This case-control study was performed on 192 preeclamptic and 196 normotensive pregnant women. Single nucleotide polymorphisms were genotyped using polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) and Tetra ARMS methods. No significant differences were observed in distribution of MTHFR C677T and FVL polymorphisms between two groups. There was a significant difference in frequency of 1298AC genotype in PE pregnant women compared to controls (P = 0.03). No 20210A allele of prothrombin gene was observed in this population. The analysis of MTHFR and factor V Leiden polymorphisms between early-onset PE (EOPE) and late-onset PE (LOPE) showed significant differences in MTHFR A1298C polymorphism (AC and CC vs AA, P = 0.012 and P = 0.006, respectively) and G1691A polymorphism...
Cortical state modulates the background activity of cortical neurons, and their evoked response t... more Cortical state modulates the background activity of cortical neurons, and their evoked response to sensory stimulation. Multiple mechanisms are involved in switching between cortical states including various neuromodulatory systems. Locus Coeruleus (LC) is one of the major neuromodulatory nuclei in the brainstem with widespread projections throughout the brain and modulates the activity of cells and networks. Here, we quantified the link between the LC spontaneous activity, cortical state and sensory processing in the rat vibrissal somatosensory "barrel" cortex (BC). We simultaneously recorded unit activity from LC and BC along with prefrontal electroencephalogram (EEG) while presenting brief whisker deflections under urethane anesthesia. The ratio of low to high frequency components of EEG (referred to as the L/H ratio) was employed to identify cortical state. We found that the spontaneous activity of LC units exhibited a negative correlation with the L/H ratio. Cross-correlation analysis revealed that changes in LC firing preceded changes in the cortical state: the correlation of the LC firing profile with the L/H ratio was maximal at an average lag of -1.2 s. We further quantified BC neuronal responses to whisker stimulation during the synchronized and desynchronized states. In the desynchronized state, BC neurons showed lower stimulus detection threshold, higher response fidelity, and shorter response latency. The most prominent change was observed in the late phase of BC evoked activity (100-400 ms post stimulus onset): almost every BC unit exhibited a greater late response during the desynchronized state. Categorization of the BC evoked responses based on LC activity (into high and low LC discharge rates) resulted in highly similar response profiles compared to categorization based on the cortical state (low and high L/H ratios). These findings provide evidence for the involvement of the LC neuromodulatory system in desynchronization of cortical state and the consequent enhancement of sensory coding efficiency.
The results of mutation screening of 24 exons of LRRK2 in 60 Iranian Parkinson&am... more The results of mutation screening of 24 exons of LRRK2 in 60 Iranian Parkinson's Disease patients are presented. The Iranian cohort represents a novel population and was notably young (average age at onset of disease: 36.0 years). Fifty sequence variations were found, seventeen of which are novel. Variations considered possibly associated with disease were screened in available family members, 145 additional patients and 220 control individuals. It was surmised that four novel sequence variations (IVS49+178A>G, p.R1725Q, p.Q1823K, and p.D2175H) may be associated with PD status, albeit they may be very rare non-disease associated variations. The four variations were all observed in the heterozygous state in early onset cases. If one or more of the variations do indeed contribute to disease status, their penetrance is expected to be low.
The results of mutation screening of 24 exons of LRRK2 in 60 Iranian Parkinson&am... more The results of mutation screening of 24 exons of LRRK2 in 60 Iranian Parkinson's Disease patients are presented. The Iranian cohort represents a novel population and was notably young (average age at onset of disease: 36.0 years). Fifty sequence variations were found, seventeen of which are novel. Variations considered possibly associated with disease were screened in available family members, 145 additional patients and 220 control individuals. It was surmised that four novel sequence variations (IVS49+178A>G, p.R1725Q, p.Q1823K, and p.D2175H) may be associated with PD status, albeit they may be very rare non-disease associated variations. The four variations were all observed in the heterozygous state in early onset cases. If one or more of the variations do indeed contribute to disease status, their penetrance is expected to be low.
The aim of this study was to examine the association of factor V Leiden, prothrombin and methylen... more The aim of this study was to examine the association of factor V Leiden, prothrombin and methylenetetrahydrofolate reductase (MTHFR) polymorphisms and preeclampsia (PE) in Southeast of Iran. This case-control study was performed on 192 preeclamptic and 196 normotensive pregnant women. Single nucleotide polymorphisms were genotyped using polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) and Tetra ARMS methods. No significant differences were observed in distribution of MTHFR C677T and FVL polymorphisms between two groups. There was a significant difference in frequency of 1298AC genotype in PE pregnant women compared to controls (P = 0.03). No 20210A allele of prothrombin gene was observed in this population. The analysis of MTHFR and factor V Leiden polymorphisms between early-onset PE (EOPE) and late-onset PE (LOPE) showed significant differences in MTHFR A1298C polymorphism (AC and CC vs AA, P = 0.012 and P = 0.006, respectively) and G1691A polymorphism of FVL(GA vs GG, P = 0.03). Moreover, the analysis of three SNPs between EOPE and controls showed significant differences in MTHFR C677T (CT + TT vs CC, P = 0.035) and MTHFR A1298C (AC and CC vs AA, P = 0.001 and P = 0.006, respectively) polymorphisms. The synergic effect of MTHFR A1298C and C677T polymorphisms showed increased risk of EOPE. MTHFR A1298C polymorphism was associated with PE. Although MTHFR C677T and FVL polymorphisms did not differ between PE patients and controls, significant differences in MTHFR A1298C, C677T and FVL polymorphisms between EOPE and LOPE/controls were observed. The synergic effect of MTHFR variants could increase PE and EOPE risk.
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Papers by Zeinab Fazlali