The microinjection of AMPA receptor antagonist into the accumbens shell, but not into the accumbens core, induces anxiolysis in an animal model of anxiety

This study investigated the effect of the AMPA receptor antagonist 6,7-dinitroquinoxaline-2,3-dione (DNQX) microinjected into the core and shell sub-regions of the accumbens nucleus (Acb), on the level of fear/anxiety and emotional learning, in female rats submitted to the elevated plus-maze (EPM), an animal model of anxiety. Bilateral microinjections of DNQX (330 and 660 ng) into the Acb shell (AP, +1.08 to +2.16) induced an anxiolytic-like effect in relation to rats microinjected with vehicle, since there was an increased percentage of entries in the open arms of the maze. The 660 ng DNQX microinjection into the Acb shell also increased the percentage of entries into the open arms in relation to 660 ng DNQX microinjection into the Acb core. Prior DNQX microinjections in both core and shell sub-regions of the Acb failed to impair the emotional learning, since the animals exhibited an increase of the open arm avoidance on EPM Trial 2 in relation to EPM trial 1. DNQX microinjections into both sub-regions of the Acb did not change the number of entries into the enclosed arms, either in the EPM Trial 1 or in the EPM Trial 2, which indicates an absence of drug-induced locomotor impairment. Similarly, DNQX microinjections into both sub-regions of the Acb failed to alter the total arm entries, rearing, grooming and head-dipping frequency. The anxiolytic-like effect induced by DNQX suggests that the AMPA receptor in the Acb shell, but not in the Acb core, may underlie anxiety regulation in the EPM.     

Relationship between pharyngeal response time and lateralized brain lesion in stroke

Objectives: To analyze the relationship between pharyngeal response time (PRT) and lateralization of brain lesions.

Methods: A Cross-sectional study. 73 videofluoroscopic swallow studies (VFSS)were conducted on patients after stroke The study subjects were divided into : group 1 (G1) consisting of 39 individuals with left cortical lesion and group 2 (G2) consisting of 34 individuals with right cortical lesions. The VFSS of G1 and G2 subjects were analyzed using puree (A) and liquid (B) consistencies, and were also subdivided into young adults and older persons. . The mean PRT was divided into times shorter and longer than 250 ms.

Results: No statistically significant difference was observed between G1 and G2 for the A and B consistencies, being obtained : G1 (A mean: 56.6 ms; B mean: 99.5 ms; A mean: 3627 ms; B mean: 1712 ms) and G2 (A mean: 79.6 ms; B mean: 110.7 ms; A mean: 2040 ms, B mean: 1529 ms), for PRT shorter (A:p = .673; B: p = 1.000) and longer (A: p = .435; B: p = .847) than 250 ms, respectively. No statistically significant difference was found regarding the variable age in the comparison between young and old adults for mean PRT according to the A and B consistencies in G1 (A: p = .260; B: p = .732) and G2 (A: p = .586; B: p = .104).

Conclusion: No relationship between PRT and lateralization of brain lesion was observed with respect to subject age and to the swallowing of different food consistencies.     

What do all personality disorders have in common? Ineffectiveness and uncooperativeness

We still lack operative and theoretically founded definitions of what a personality disorder (PD) is, as well as empirically validated and feasible instruments to measure the disorder construct. The Temperament and Character Inventory (TCI) is the only personality instrument that explicitly distinguishes personality style and disordered functioning. Here, we seek to (1) confirm in a clinical sample that the character dimensions of the TCI capture a general construct of PD across all specific PD subtypes, (2) determine whether such core features can be used to detect the presence of PD, and (3) analyze whether such detection is affected by the presence and severity of Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition (DSM-IV) Axis I symptoms. Two hundred five anxious/depressed outpatients were evaluated with the Structural Clinical Interview for DSM-IV Axis I and II Disorders. Assessment also included the TCI, the Hamilton rating scales for depression and anxiety, and the Panic and Agoraphobia Scale. Sixty-one patients (29.8%) were diagnosed as having a DSM-IV PD. Self-directedness and Cooperativeness, but no other TCI dimensions, predicted the presence of PD (Nagelkerke R(2) = 0.35-0.45) and had a moderate diagnostic utility (kappa = 0.47-0.58) when Axis I symptoms were absent or mild. However, accuracy decreased in anxious or depressed patients. Our study supports the hypothesis of a disorder construct that is not related to the intensity of any specific PD subtype but which is common to all PDs. This construct relies largely on internal representations of the self revealing ineffectiveness and uncooperativeness.     

Region-specific control of microglia by adenosine A2A receptors: uncoupling anxiety and associated cognitive deficits in female rats

Epidemiologic studies have provided compelling evidence that prenatal stress, through excessive maternal glucocorticoids exposure, is associated with psychiatric disorders later in life. We have recently reported that anxiety associated with prenatal exposure to dexamethasone (DEX, a synthetic glucocorticoid) correlates with a gender-specific remodeling of microglia in the medial prefrontal cortex (mPFC), a core brain region in anxiety-related disorders. Gender differences in microglia morphology, the higher prevalence of anxiety in women and the negative impact of anxiety in cognition, led us to specifically evaluate cognitive behavior and associated circuits (namely mPFC-dorsal hippocampus, dHIP), as well as microglia morphology in female rats prenatally exposed to dexamethasone (in utero DEX, iuDEX). We report that iuDEX impaired recognition memory and deteriorated neuronal synchronization between mPFC and dHIP. These functional deficits are paralleled by microglia hyper-ramification in the dHIP and decreased ramification in the mPFC, showing a heterogeneous remodeling of microglia morphology, both postnatally and at adulthood in different brain regions, that differently affect mood and cognition. The chronic blockade of adenosine A_2A receptors (A_2AR), which are core regulators of microglia morphology and physiology, ameliorated the cognitive deficits, but not the anxiety-like behavior. Notably, A_2AR blockade rectified both microglia morphology in the dHIP and the lack of mPFC-dHIP synchronization, further heralding their role in cognitive function.     

Oligodendrocytes in mouse corpus callosum are coupled via gap junction channels formed by connexin47 and connexin32

According to previously published ultrastructural studies, oligodendrocytes in white matter exhibit gap junctions with astrocytes, but not among each other, while in vitro oligodendrocytes form functional gap junctions. We have studied functional coupling among oligodendrocytes in acute slices of postnatal mouse corpus callosum. By whole‐cell patch clamp we dialyzed oligodendrocytes with biocytin, a gap junction‐permeable tracer. On average 61 cells were positive for biocytin detected by labeling with streptavidin‐Cy3. About 77% of the coupled cells stained positively for the oligodendrocyte marker protein CNPase, 9% for the astrocyte marker GFAP and 14% were negative for both CNPase and GFAP. In the latter population, the majority expressed Olig2 and some NG2, markers for oligodendrocyte precursors. Oligodendrocytes are known to express Cx47, Cx32 and Cx29, astrocytes Cx43 and Cx30. In Cx47‐deficient mice, the number of coupled cells was reduced by 80%. Deletion of Cx32 or Cx29 alone did not significantly reduce the number of coupled cells, but coupling was absent in Cx32/Cx47‐double‐deficient mice. Cx47‐ablation completely abolished coupling of oligodendrocytes to astrocytes. In Cx43‐deficient animals, oligodendrocyte‐astrocyte coupling was still present, but coupling to oligodendrocyte precursors was not observed. In Cx43/Cx30‐double deficient mice, oligodendrocyte‐to‐astrocyte coupling was almost absent. Uncoupled oligodendrocytes showed a higher input resistance. We conclude that oligodendrocytes in white matter form a functional syncytium predominantly among each other dependent on Cx47 and Cx32 expression, while astrocytic connexins expression can promote the size of this network. © 2010 Wiley‐Liss, Inc.     

Evidence for a relatively high proportion of DM2 mutations in a large group of Polish patients

Introduction

Myotonic dystrophies (DMs) type 1 (DM1) and type 2 (DM2) are autosomal dominant, multisystem disorders, considered the most common dystrophies in adults. DM1 and DM2 are caused by dynamic mutations in the DMPK and CNBP genes, respectively.

Caregivers of patients with amyotrophic lateral sclerosis: investigating quality of life,caregiver burden,service engagement,and patient survival

Few studies in amyotrophic lateral sclerosis (ALS) have profiled disease-specific features of the condition in conjunction with assessment of caregivers’ burden, distress, quality of life, and investigated patient survival. Eighty-four ALS patients and their primary caregivers were enrolled. Patients completed ALS-specific measures of physical and cognitive function, while caregivers completed measures of anxiety, depression, caregiver burden, and quality of life. Patient-caregiver dyads were interviewed about their health-service utilisation. Survival data were obtained through the Irish register for ALS. Participants were dichotomised into low/high groups according to the severity of self-reported caregiver burden, based on statistically derived cut-off scores. High-burdened caregivers (n = 43) did not significantly differ from low-burdened caregivers (n = 41) with respect to disease-specific characteristics, i.e., ALSFRS-R, bulbar- or spinal-onset ALS, disease duration, or survival data. However, significant differences were reported on subjective measures of anxiety (p < 0.000), depression (p < 0.001), distress (p < 0.000), and quality of life (p < 0.000). These data demonstrate the limited impact of ALS patient-related variables, i.e., ALSFRS-R and onset, on caregiver burden in ALS, and identify the importance of the psychological composition of caregivers. This study suggests that the subjective experience of individual caregivers is an important factor influencing the severity of experienced caregiver burden.