Phosphorylation of the Third Intracellular Loop of the Mouse α1b-Adrenergic Receptor by cAMP-dependent Protein Kinase

The third intracellular loop of adrenergic receptors has been implicated in their interaction with guanine nucleotide-binding proteins (G proteins). One of the mechanisms involved in the modulation of receptor function is the phosphorylation of specific residues by intracellular kinases.

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-Adrenergic receptor is phosphorylated in vitro by cAMP-dependent protein kinase (PKA), although its physiological effect remains to be determined. We have produced fusion proteins formed by glutathione S-transferase and sequences of the third intracellular loop of mouse

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-,

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-, and

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-adrenergic receptor subtypes, and used them as substrates for PKA. Only the fusion protein containing the

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sequence was phosphorylated in vitro by this kinase. Site-directed mutagenesis of a serine (homologue to serine 278 of the rat sequence, RSS) to an alanine residue precluded phosphorylation by PKA.     

Increased Levels of mRNA for β- but not α-Subunit of Calmoduline Kinase II Following Kindled Seizures

We studied levels of mRNA for the

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- and

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-subunits of calmodulin (CaM) kinase II using the amygdaloid kindling model of epilepsy. There were significant increases in mRNA for the

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-subunit of CaM kinase II in the hippocampus 4—24 h after stage 5-kindled seizures. Moreover, this mRNA was significantly increased by 20.0–26.5% in the bilateral dentate gyrus 8 to 24 h after kindled seizures. The

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-subunit mRNA was also significantly increased by 13.5–19.0% in the CA3 on the side ipsilateral to the stimulation, 4 to 8 h after kindled seizures. mRNA for the

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-subunit of CaM kinase II was not significantly changed in the regions examined for up to 24 h after the kindled seizures. These results suggest that CaM kinase II mediates the molecular processes that follow kindled seizures. It is possible that increases in CaM kinase II-dependent protein phosphorylation are associated with the plastic changes in kindling.     

Characterization of α,β-Methylene ATP Binding Sites in Mouse Crude Synaptic Membranes

Since ATP has been reported to be a potent excitatory transmitter in the mammalian central nervous system (CNS), we studied the neurochemical characters of the binding sites of

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,

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-methylene ATP, an agonist of P_2X receptors, in mouse crude synaptic membranes. ATP and its related compounds inhibited [³H]

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,

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-methylene ATP binding in a concentration-dependent manner. The potency order in the inhibition of the binding was as follows;

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,

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-methylene

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>

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> ATP ≥ ADP >

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,

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-methylene ATP UTP > 2-methylthio ATP. And adenosine did not affect the binding. The order was different from those reported in peripheral tissues. And Sr²⁺, Ca²⁺, Mg²⁺, and Cd²⁺ enhanced the binding. These results suggest that

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,

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-methylene ATP binding sites in CNS have different characters from those in peripheral tissues.     

The Effect of Stimulus Parameters on TMS–EEG Muscle Artifacts

BackgroundWhen transcranial magnetic stimulation (TMS) is delivered close to the lateral aspects of the head, large-amplitude (～10–1000 μV) biphasic electroencephalographic (EEG) deflections, peaking at around 4–10 and 8–20 ms, appear.ObjectiveTo characterize the spatiotemporal features of these artifacts, to quantify the effect of stimulus parameters on them, and thus, to study the feasibility of different measurement procedures to decrease the artifacts online. Furthermore, to show that these deflections, when measured with a sample-and-hold system, mainly result from excitation of cranial muscles.MethodsThree subjects received TMS to 16 sites over the left hemisphere. TMS-compatible EEG was recorded simultaneously. Four other subjects received TMS to M1 with different coil rotation and tilt angles and stimulation intensities. We also stimulated a conductive phantom and recorded simultaneous EEG to exclude the possibility of residual electromagnetic artifacts.ResultsThe artifacts were largest when the stimulator was placed above cranial muscles, whereas stimulation of relatively central sites far from the muscles produced muscle artifact-free data. The laterally situated EEG channels were most severely contaminated. The artifacts were significantly reduced when reducing the intensity or when tilting or rotating the coil so that coil wings moved further away from the temporal muscle, while brain responses remained visible. Stimulation of the phantom did not produce such large-amplitude biphasic artifacts.ConclusionAltering the stimulation parameters can reduce the described artifact, while brain responses can still be recorded. The early, laterally appearing, large biphasic TMS-evoked EEG deflections recorded with a sample-and-hold system are caused by cranial muscle activation.     

The Effect of Methylphenidate and Placebo on Eye–Hand Coordination Functioning and Handwriting of Children with Attention Deficit Hyperactivity Disorder

Israeli children who were diagnosed as having attention deficit hyperactivity disorder participated in the study. The children were assessed three times in a specially constructed battery of tests. The battery of tests included variables assessing eye–hand coordination skills, writing, and behavioral assessment of the teacher. The design was in the format of a double blind, randomized, crossover, placebo-control procedure. The results showed that methylphenidate (MPH) improved some cognitive functions of eye–hand coordination slightly better than placebo. In addition, behavior variables assessed by the teachers improved only under the influence of MPH.     

Effect of type-2 astrocytes on the viability of dorsal root ganglion neurons and length of neuronal processes简

The role of type-2 astrocytes in the repair of central nervous system injury remains poorly un- derstood. In this study, using a relatively simple culture condition in vitro, type-2 astrocytes, differentiated from oligodendrocyte precursor cells by induction with bone morphogenetic pro- tein-4, were co-cultured with dorsal root ganglion neurons. We examined the effects of type-2 astrocytes differentiated from oligodendrocyte precursor cells on the survival and growth of dorsal root ganglion neurons. Results demonstrated that the number of dorsal root ganglion neurons was higher following co-culture of oligodendrocyte precursor cells and type-2 astrocytes than when cultured alone, but lower than that of neurons co-cultured with type-1 astrocytes. The length of the longest process and the length of all processes of a single neuron were shortest in neurons cultured alone, followed by neurons co-cultured with type-2 astroc~es, then neurons co-cultured with oligodendrocyte precursor cells, and longest in neurons co-cultured with type-1 astrocytes. These results indicate that co-culture with type-2 astrocytes can increase neuronal survival rate and process length. However, compared with type-1 astrocytes and oligodendrocyte precursor cells, the promotion effects of type-2 astrocytes on the growth of dorsal root ganglion neurons were weaker.     

The Defendant with the Prison Tattoo: The Effect of Tattoos on Mock Jurors’ Perceptions

Little is known about the potential for tattoos to bias how defendants are perceived. In Study 1, the participants (n = 30) viewed photographs of five men with a tattoo (prison or modern style) on the face and neck or arm. Individuals with prison-style tattoos were perceived more negatively, especially when the tattoos were located on the face and neck compared to the arm. In Study 2, participants (n = 120) were shown a photograph of a defendant who either had a prison-style tattoo or no tattoo, and read a scenario describing a physical assault (with either strong or weak evidence). Perceptions of defendant dangerousness mediated the relationship between the presence of a tattoo and mock jurors’ perceptions of guilt.     

Effect of 200 μG/day of vitamin k1 on the variability of anticoagulation control in patients on warfarin: A randomized controlled trial

Background

Controversy exists whether low-dose vitamin K supplementation can improve anticoagulation control in patients with unstable anticoagulation under warfarin. In a single- centre randomized, double-blind, placebo-controlled study, we evaluated the effectiveness of 200 μg/day of vitamin K1 in patients with unstable control under warfarin.

Methods

Effectiveness of Vitamin K1 supplementation was primarily assessed by the percentage (%) of Time-in-Therapeutic-Range (TTR) and secondarily by the standard deviation (SD) of the patient’s INR values; the proportion of out-of-range INRs; and the number of dose changes on warfarin. Their change scores were obtained by subtracting the mean value in the 6 months pre-randomization from the mean value in the 6 months post-randomization. Multivariable linear-regressions identified factors associated with anticoagulation instability.

Results

Fifty out of 54 patients were analyzed (intervention: n = 26; placebo: n = 24). Most indications (87%) for anticoagulation were venous thromboembolism (VTE). The intervention was associated with a greater reduction in the change scores for the SD of INRs between the pre and post-randomization periods compared with placebo. The mean change score was -0.259 ± 0.307 with the intervention and -0.046 ± 0.345 with placebo (p = 0.026). There was no effect on the change scores of the (%) TTR (p = 0.98), the number of INRs out-of-range (p = 0.58) and the number of dose changes (p = 0.604). Factors independently associated with increased variability in the SD of INRs were increased alcoholic drinks/week (p = 0.017), dosing errors (p = 0.0009) and missed INR appointments (p = 0.035).

Conclusion

Vitamin K1 supplementation reduces the SD of INRs as an indicator of the variability in anticoagulation control in patients treated with warfarin for VTE.     

Posttraumatic Stress Disorder and Use of Psychiatric and Alcohol Related Services: The Effect of the 2004–2005 Florida Hurricane Seasons on Veterans

The purpose of this study was to document preliminary findings of the association between posttraumatic stress disorder (PTSD), mental health service use, and alcohol related health visits among veterans following 2004–2005 Florida hurricane seasons. A retrospective review of the Veterans Health Administration Medical SAS Outpatient Dataset was conducted to identify veterans residing in Florida during the 2004–2005 hurricane seasons with a history of PTSD and/or PTSD and a substance use disorder. It was found that veterans with PTSD residing in counties affected by hurricanes demonstrated an immediate 28 % increase in use of mental health services following hurricane landfall versus veterans residing in non-hurricane affected counties (+28.0 vs. ?6.5 %, p = 0.001). Additionally, veterans residing in affected counties were found to use more group psychotherapy treatment sessions overall (30.3 vs. 27.2 %, p = 0.001). Of note, veterans with PTSD experienced a ?0.16 per month (p = 0.114) decrease in alcohol related visits following the 2004 hurricane season. These findings provide insight into the mental health needs of veterans with PTSD following a disaster and can inform delivery of services to veterans with PTSD and alcohol related issues in disaster prone areas.     

The Effect of Vitamin A Supplementation on FoxP3 and TGF-β Gene Expression in Avonex-Treated Multiple Sclerosis Patients

Journal of Molecular Neuroscience - Multiple sclerosis (MS) is an autoinflammatory condition of the central nervous system with impaired T helper (Th)17 and regulatory T cell (Treg) balance that is...     

The impact of synapsins on synaptic plasticity and cognitive behaviors

Synapsins are a family of phosphoproteins specifically associated with the cytoplasmic surface of the synaptic vesicle membrane, appearing to regulate neurotransmitter release, the formation and maintenance of synaptic contacts. They could induce the change of the synaptic plasticity to regulate various adaptation reactions, and change the cognitive behaviors. So we presume that if some cognitive behavior are damaged, synapsins would be changed as well. This gives us a new recognition of better diagnosis and therapy of cognitive disorder desease.     

The Effect of Docosahexaenoic Acid on Visual Evoked Potentials in a Mouse Model of Parkinson’s Disease: The Role of Cyclooxygenase-2 and Nuclear Factor Kappa-B

This study aimed to investigate the effect of docosahexaenoic acid (DHA) on visual evoked potentials (VEPs) in a mice model of Parkinson’s disease (PD). Mice model was created by 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) and DHA was given by gavage. Cyclooxygenase-2 (COX-2), caspase-3 activities, nuclear factor kappa-B (NF-κB) and prostaglandin E2 (PGE2) levels were determined in substantia nigra (SN) and retina. Cyclooxygenase-2 intensities were also determined immunohistochemically. The tyrosine hydroxylase (TH) immunolabelling was significantly decreased in MPTP group compared to control. Docosahexaenoic acid decreased dopaminergic neuron death in MPTP + DHA group when compared to MPTP group. Mice treated with MPTP showed motor deficits as compared to control. Significant improvement was observed in MPTP + DHA group when compared to MPTP group. Treatment with MPTP significantly increased the activity of COX-2 and total COX in SN when compared to the control group. Docosahexaenoic acid caused a significant decrease in total COX and COX-2 activity in SN of mice given MPTP. Cyclooxygenase-2 showed strong immunostaining in MPTP group when compared to other groups in SN. Levels of PGE2 increased in MPTP group when compared to control in SN. Docosahexaenoic acid treatment in MPTP group reduced PGE2 in SN. Nuclear factor kappa-B levels were found to be decreased in SN of MPTP group. The mean latencies of P1, N1, P2, N2, P3, N3, P4, N4, and P5 VEP components were significantly prolonged in MPTP group when compared to control. In MPTP + DHA group, the mean latencies of all components except P5 returned to control values. Current data shows that DHA treatment improves prolonged VEPs latencies and locomotor activity.     

Effect of α2A-adrenoceptor C-1291G genotype and maltreatment on hyperactivity and inattention in adolescents

The C-1291G polymorphism (rs1800544) in the promoter region of the α_2A-adrenoceptor gene (ADRA2A) has been associated with attention deficit and hyperactivity in clinical samples. We have examined the effect of ADRA2A C-1291G on inattentive, hyperactive and aggressive behaviour in a population representative cohort of healthy schoolchildren, and possible interaction of genotype with family relations. Ratings on aggressiveness, motor restlessness and concentration difficulties were obtained from the class teachers by using the Hyperactivity Scale of af Klinteberg, and the teacher-report version of SNAP-IV. The relations in the family were reported by children. Symptom scores, self-reports and genotype data of 429 15-years old children (196 boys, 233 girls) were available for analysis. There was a significant interaction effect of maltreatment and the ADRA2A genotype on behavioural functioning in 15 years old boys. Boys with CC genotype and higher score of maltreatment demonstrated more overactive behaviour and concentration difficulties than boys with CC genotype and low maltreatment score. They also had more inattentive symptoms measured by SNAP-IV. Among boys with low maltreatment score, subjects with CC genotype demonstrated less overactivity than G allele carriers. In girls, the G allele carriers did not differ from the CC genotype, but in maltreated girls with GG genotype aggression and inattention symptoms were reduced, and the score of aggressive behaviour was also lower compared to maltreated girls with CC genotype. Our data suggest that family environmental factors may act together with the α_2A-adrenoceptor genotype to increase the expression of hyperactive and inattentive symptoms in adolescents.     

Effect of calcitonin gene-related peptide and nerve growth factor on spatial learning and memory abilities of rats following focal cerebral ischemia/reperfusion

BACKGROUND: Calcitonin gene-related peptide (CGRP) and nerve growth actor (NGF) cam improve spatial learning and memory abilities of rats with cerebral ischemia/reperfusion; however, the effect of combination of them on relieving learning and memory injury following cerebral ischemia/reperfusion should be further studied. OBJECTIVE: To study the effects of exogenous CGRP and NGF on learning and memory abilities of rats with focal cerebral ischemia/reperfusion. DESIGN: Randomized controlled animal study. SETTING: Department of Neurosurgery, the Second Hospital of Xiamen; Department of Neurosurgery, the Second Affiliated Hospital of China Medical University; Department of Neurobiology, Basic Medical College of China Medical University. MATERIALS: A total of 30 healthy male SD rats, aged 8 weeks, of clean grade, weighing 250-300 g, were provided by Experimental Animal Department of China Medical University. All rats were randomly divided into sham-operation group, ischemia/reperfusion group and treatment group with 10 in each group. The main reagents were detailed as the follows: 100 g/L chloral hydrate, 0.5 mL CGRP (2 mg/L, Sigma Company, USA), and NGF (1× 106 U/L, 0.5 mL, Siweite Company, Dalian). METHODS: The experiment was carried out in the Department of Neurobiology, Basic Medical College of China Medical University from February to July 2005. Rat models of middle cerebral artery occlusion were established by method of occlusion, 2 hours after that rats were anesthetized and the thread was slightly drawn out for 10 mm under direct staring to perform reperfusion. Rats in the ischemia/reperfusion group received intraperitoneal injection of 1 mL saline via the abdomen at two hours later, while rats in the treatment group at 2 hours later received intraperitoneal injection of 2 mg/L CGRP (0.5 mL) and 1×106 U/L NGF (0.5 mL) once a day for 10 successive days. First administration was accomplished within 15 minutes after ischemia/reperfusion. Rats in the sham-operation group were separated of the vessels without occlusion or administration. The neural function was evaluated with Zea Longa 5-grade scale. Animals with the score of one, two and three points received Morris water-maze test to measure searching time on platform (omitting platform-escaping latency). Meanwhile, leaning and memory abilities of animals were reflected through testing times of passing through platform per minute. MAIN OUTCOME MEASURES: Experimental results of omitting platform-escaping latency and spatial probe. RESULTS: Three and two rats in the ischemia/reperfusion group and treatment group respectively were not in accordance with the criteria in the process, and the rest were involved in the final analysis. ① Comparisons of platform-escaping latency during Morris water-maze test in all the three groups: Ten days after modeling, the platform-escaping latency in the ischemia/reperfusion group was obviously longer than that in sham-operation group (P < 0.01), and was significantly shorter than that in the treatment group (P < 0.01). ② Comparisons of times of passing through platform in all the three groups: Times of passing through platform were remarkably less in the ischemia/reperfusion group than those in the sham-operation group [(1.79±0.39), (4.30±0.73) times/minute, P < 0.01], and those were markedly more in the treatment group than the ischemia/reperfusion group [(3.16±1.03), (1.79±0.39) times/minute, P < 0.01]. CONCLUSION: CGRP and NGF are capable of ameliorating the abilities of spatial learning and memory in MCAO rats, which indicates that CGRP and NGF can protect ischemic neurons.