Using whole cell patch-clamp recording in a rat brain stem slice preparation, we found that gamma-aminobutyric acid (GABA) and glycine act as cotransmitters to hypoglossal motoneurons (HMs). Focal application of GABA and glycine onto a single HM revealed that GABAA and glycine receptors are present on the same neuron. To demonstrate that HMs receive both GABAergic and glycinergic synaptic inputs, we simultaneously recorded GABAA- and glycine-receptor-mediated spontaneous miniature inhibitory postsynaptic currents (mIPSCs) in single HMs. GABAergic and glycinergic mIPSCs were differentiated based on their kinetics and modulation by pentobarbital. Specifically, GABAA-receptor-mediated events decayed more slowly than glycine-receptor-mediated events. GABAergic response decay kinetics were prolonged by pentobarbital, whereas glycinergic response decay kinetics remained unchanged. The distinct kinetics of the glycine- and GABAA-receptor-mediated synaptic events allowed us to record dual component mIPSCs, mIPSCs that are mediated by both receptor types. These data suggest that GABA and glycine are colocalized in the same presynaptic vesicle and are coreleased from presynaptic terminals opposed to motoneurons.
Background: Previous cross-sectional fMRI studies in subjects with prodromal Alzheimer disease
Disclosure of abuse, such as what happens with abuse assessment, was associated with the same reduction in violence and increase in safety behaviors as a nurse case management intervention. Simple assessment for abuse and offering of referrals has the potential to interrupt and prevent recurrence of IPV and associated trauma.
ABSTRACT. Objective. To compare the behaviors of black, white, and Hispanic children who were 18 months to 18 years of age and exposed to intimate partner violence with an age-and ethnically similar sample of children who were not exposed to violence and to compare both exposed and nonexposed children to normative samples.Methods. As part of a study on treatments for abused women in primary care public health clinics and Women, Infants and Children clinics in a large urban area, 258 abused mothers completed the Child Behavior Checklist (CBCL) on 1 of their randomly selected children between the ages of 18 months and 18 years. An ethnically similar sample of 72 nonabused mothers also completed the CBCL. The CBCL is a standardized instrument that provides a parental report of the extent of a child's behavioral problems and social competencies. The CBCL consists of a form for children 18 months to 5 years and a version for ages 6 to 18 years. The CBCL is orally administered to a parent, who rates the presence and frequency of certain behaviors on a 3-point scale (0 ؍ not true, 1 ؍ somewhat or sometimes true, and 2 ؍ very true or often true). The time period is the last 6 months for the child 6 to 18 years of age and 2 months for the child 18 months to 5 years of age. Examples of behaviors for the child age 6 to 18 years include "gets in many fights," "truancy, skips school." Examples of behaviors for the child 18 months to 5 years of age include "cruel to animals," "physically attacks people," and "doesn't want to sleep alone." Both forms of the CBCL consist of 2 broadband factors of behavioral problems: internalizing and externalizing with mean scale scores for national normative samples as well as clinically referred and nonreferred samples of children. Internalizing behaviors include anxiety/depression, withdrawal, and somatic complaints. Externalizing behaviors include attention problems, aggressive behavior, and rule-breaking actions. Behavior scales yield a score of total behavioral problems. Scores are summed and then converted to normalized T scores. T scores >60 are within the borderline/clinical referral range-higher scores represent more deviant behavior. Multivariate analyses of variance (MANOVAs) were used to determine whether children from abused mothers differed significantly in their internalizing behaviors, externalizing behaviors, and total behavior problems from children of nonabused mothers. One sample t tests were used to compare children from abused and nonabused mothers to the matched clinically referred and nonreferred normative sample. Four pair-wise comparisons were considered: 1) children from abused women to referred norm, 2) children from abused women to nonreferred norm, 3) children from nonabused women to referred norm, and 4) children from nonabused to nonreferred norm. The internal, external, and total behavior problem T scores were dichotomized into a referral status: nonreferred ؍ T score < 60, referred ؍ T score > 60. Frequencies and percentages were used to describe th...
The hypothesis that the neural network supporting successful episodic memory retrieval overlaps with the regions involved in episodic encoding has garnered much interest; however, the role of the posteromedial regions remains to be fully elucidated. Functional magnetic resonance imaging (fMRI) studies during successful encoding typically demonstrate deactivation of posteromedial cortices, whereas successful retrieval of previously encoded information has been associated with activation of these regions. Here, we performed an event-related fMRI experiment during an associative face-name encoding and retrieval task to investigate the topography and functional relationship of the brain regions involved in successful memory processes. A conjunction analysis of novel encoding and subsequent successful retrieval of names revealed an anatomical overlap in bilateral posteromedial cortices. In this region, a significant negative correlation was found: Greater deactivation during encoding was related to greater activation during successful retrieval. In contrast, the hippocampus and prefrontal cortex demonstrated positive activation during both encoding and retrieval. Our results provide further evidence that posteromedial regions constitute critical nodes in the large-scale cortical network subserving episodic memory. These results are discussed in relation to the default mode hypothesis, the involvement of posteromedial cortices in successful memory formation and retention, as well as potential implications for aging and neurodegenerative disease.
Aspirin (ASA) triggers a switch in the biosynthesis of lipid mediators, inhibiting prostanoid production and initiating 15-epi-lipoxin generation through the acetylation of cyclooxygenase II. These aspirin-triggered lipoxins (ATL) may mediate some of ASA's beneficial actions and therefore are of interest in the search for novel antiinf lammatories that could manifest fewer unwanted side effects. Here, we report that design modifications to native ATL structure prolong its biostability in vivo. In mouse whole blood, ATL analogs protected at carbon 15 [15(R͞S)-methyllipoxin A 4 (ATLa 1 )] and the omega end [15-epi-16-(paraf luoro)-phenoxy-LXA 4 (ATLa 2 )] were recoverable to Ϸ90 and 100% at 3 hr, respectively, compared with a Ϸ40% loss of native lipoxin A 4 . ATLa 2 retains bioactivity and, at levels as low as Ϸ24 nmol͞mouse, potently inhibited tumor necrosis factor-␣-induced leukocyte recruitment into the dorsal air pouch. Inhibition was evident by either local intra-air pouch delivery (Ϸ77% inhibition) or systemic delivery by intravenous injection (Ϸ85% inhibition) and proved more potent than local delivery of ASA. Rank order for inhibiting polymorphonuclear leukocyte infiltration was: ATLa 2 (10 g, i.v.) ϷATLa 2 (10 g, local) Ϸdexamethasone (10 g, local) >ASA (1.0 mg, local). Applied topically to mouse ear skin, ATLa 2 also inhibited polymorphonuclear leukocyte infiltration induced by leukotriene B 4 (Ϸ78% inhibition) or phorbol ester (Ϸ49% inhibition), which initiates endogenous chemokine production. These results indicate that this f luorinated analog of natural aspirin-triggered lipoxin A 4 is bioavailable by either local or systemic delivery routes and is a more potent and precise inhibitor of neutrophil accumulation than is ASA.
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