Combined thirty-day exposure to thioacetamide and choline-deprivation alters serum antioxidant status and crucial brain enzyme activities in adult rats

Choline (Ch) is an essential nutrient that seems to be involved in a wide variety of metabolic reactions and functions that affect the nervous system, while thioacetamide (TAA) is a well-known hepatotoxic agent. The induction of prolonged Ch-deprivation (CD) in rats receiving TAA (through the drinking water) provides an experimental model of mild progressive hepatotoxicity that could simulate commonly-presented cases in clinical practice. In this respect, the aim of this study was to investigate the effects of a 30-day dietary CD and/or TAA administration (300 mg/L of drinking water) on the serum total antioxidant status (TAS) and the activities of brain acetylcholinesterase (AChE), Na⁺,K⁺-ATPase and Mg²⁺-ATPase of adult rats. Twenty male Wistar rats were divided into four groups: A (control), B (CD), C (TAA), D (CD+TAA). Dietary CD was provoked through the administration of Ch-deficient diet. Rats were sacrificed by decapitation at the end of the 30-day experimental period and whole brain enzymes were determined spectrophotometrically. Serum TAS was found significantly lowered by CD (−11% vs Control, p < 0.01) and CD+TAA administration (−19% vs Control, p < 0.001), but was not significantly altered due to TAA administration. The rat brain AChE activity was found significantly increased by TAA administration (+11% vs Control, p < 0.01), as well as by CD+TAA administration (+14% vs Control, p < 0.01). However, AChE was not found to be significantly altered by the 30-day dietary CD. On the other hand, CD caused a significant increase in brain Na⁺,K⁺-ATPase activity (+16% vs Control, p < 0.05) and had no significant effect on Mg²⁺-ATPase. Exposure to TAA had no significant effect on Na⁺,K⁺-ATPase, but inhibited Mg²⁺-ATPase (−20% vs Control, p < 0.05). When administered to CD rats, TAA caused a significant decrease in Na⁺,K⁺-ATPase activity (−41% vs Control, p < 0.001), but Mg²⁺-ATPase activity was maintained into control levels. Our data revealed that an adult-onset 30-day dietary-induced CD had no effect on AChE activity. Treatment with TAA not only reversed the stimulatory effect of CD on adult rat brain Na⁺,K⁺-ATPase, but caused a dramatic decrease in its activity (−41%). Previous studies have linked this inhibition with metabolic phenomena related to TAA-induced fulminant hepatic failure and encephalopathy. Our data suggest that CD (at least under the examined 30-day period) is an unfavorable background for the effect of TAA-induced hepatic damage on Na⁺,K⁺-ATPase activity (an enzyme involved in neuronal excitability, metabolic energy production and neurotransmission).     

A qualitative study on the experiences of mothers caring for their children with thalassemia in Athens, Greece

This qualitative study investigated the caregiving experiences of mothers of children with thalassemia. Using a semistructured questionnaire, the researchers interviewed a convenient sample of 19 mothers who have children with thalassemia. A considerable failure to provide information regarding carrier testing prior to marriage or genetic screening for thalassemia during early pregnancy at the time of the participants' pregnancies was noted. Emotional distress, fear of death, and difficulties in dealing with feelings were some of the mothers' concerns. Although they reported that support was provided, approximately half of the subjects wished that support be offered on a more regular basis. Furthermore, most of the mothers stressed that, owing to the tremendous shortage of nursing staff, support services provided by nurses are difficult to obtain.     

N-arachidonoyl glycine suppresses Na+/Ca2+ exchanger-mediated Ca2+ entry into endothelial cells and activates BKCa channels independently of GPCRs

Background and Purpose

N-arachidonoyl glycine (NAGly) is a lipoamino acid with vasorelaxant properties. We aimed to explore the mechanisms of NAGly''s action on unstimulated and agonist-stimulated endothelial cells.

Experimental Approach

The effects of NAGly on endothelial electrical signalling were studied in combination with vascular reactivity.

Key Results

In EA.hy926 cells, the sustained hyperpolarization to histamine was inhibited by the non-selective Na⁺/Ca²⁺ exchanger (NCX) inhibitor bepridil and by an inhibitor of reversed mode NCX, KB-R7943. In cells dialysed with Cs⁺-based Na⁺-containing solution, the outwardly rectifying current with typical characteristics of NCX was augmented following histamine exposure, further increased upon external Na⁺ withdrawal and inhibited by bepridil. NAGly (0.3–30 μM) suppressed NCX currents in a URB597- and guanosine 5′-O-(2-thiodiphosphate) (GDPβS)-insensitive manner, [Ca²⁺]_i elevation evoked by Na⁺ removal and the hyperpolarization to histamine. In rat aorta, NAGly opposed the endothelial hyperpolarization and relaxation response to ACh. In unstimulated EA.hy926 cells, NAGly potentiated the whole-cell current attributable to large-conductance Ca²⁺-activated K⁺ (BK_Ca) channels in a GDPβS-insensitive, paxilline-sensitive manner and produced a sustained hyperpolarization. In cell-free inside-out patches, NAGly stimulated single BK_Ca channel activity.

Conclusion and Implications

Our data showed that NCX is a Ca²⁺ entry pathway in endothelial cells and that NAGly is a potent G-protein-independent modulator of endothelial electrical signalling and has a dual effect on endothelial electrical responses. In agonist pre-stimulated cells, NAGly opposes hyperpolarization and relaxation via inhibition of NCX-mediated Ca²⁺ entry, while in unstimulated cells, it promotes hyperpolarization via receptor-independent activation of BK_Ca channels.     

In vivo molecular imaging of the GABA/benzodiazepine receptor complex in the aged rat brain

The GABA-ergic system, known to regulate neural tissue genesis during cortical development, has been postulated to play a role in cerebral aging processes. Using in vivo molecular imaging and voxel-wise quantification, we aimed to assess the effects of aging on the benzodiazepine (BDZ) recognition site of the GABA(A) receptor. To visualize BDZ site availability, [(11)C]-flumazenil microPET acquisitions were conducted in young and old rats. The data were analyzed and region of interest analyses were applied to validate the voxel-wise approach. We observed decreased [(11)C]-flumazenil binding in the aged rat brains in comparison with the young control group. More specifically, clusters of reduced radioligand uptake were detected in the bilateral hippocampus, cerebellum, midbrain, and bilateral frontal and parieto-occipital cortex. Our results support the pertinence of voxel-wise quantification in the analysis of microPET data. Moreover, these findings indicate that the aging process involves declines in neural BDZ recognition site availability, proposed to reflect alterations in GABA(A) receptor subunit polypeptide expression.     

Amplitude spectrum EEG signal evidence for the dissociation of motor and perceptual spatial working memory in the human brain

This study investigated the question whether spatial working memory related to movement plans (motor working memory) and spatial working memory related to spatial attention and perceptual processes (perceptual spatial working memory) share the same neurophysiological substrate or there is evidence for separate motor and perceptual working memory streams of processing. Towards this aim, ten healthy human subjects performed delayed responses to visual targets presented at different spatial locations. Two tasks were attained, one in which the spatial location of the target was the goal for a pointing movement and one in which the spatial location of the target was used for a perceptual (yes or no) change detection. Each task involved two conditions: a memory condition in which the target remained visible only for the first 250 ms of the delay period and a delay condition in which the target location remained visible throughout the delay period. The amplitude spectrum analysis of the EEG revealed that the alpha (8–12 Hz) band signal was smaller, while the beta (13–30 Hz) and gamma (30–45 Hz) band signals were larger in the memory compared to the non-memory condition. The alpha band signal difference was confined to the frontal midline area; the beta band signal difference extended over the right hemisphere and midline central area, and the gamma band signal difference was confined to the right occipitoparietal area. Importantly, both in beta and gamma bands, we observed a significant increase in the movement-related compared to the perceptual-related memory-specific amplitude spectrum signal in the central midline area. This result provides clear evidence for the dissociation of motor and perceptual spatial working memory.     

Stigma in youth with Tourette’s syndrome: a systematic review and synthesis

Tourette’s syndrome (TS) is a childhood onset neurodevelopmental disorder, characterised by tics. To our knowledge, no systematic reviews exist which focus on examining the body of literature on stigma in association with children and adolescents with TS. The aim of the article is to provide a review of the existing research on (1) social stigma in relation to children and adolescents with TS, (2) self-stigma and (3) courtesy stigma in family members of youth with TS. Three electronic databases were searched: PsycINFO, PubMed and Web of Science. Seventeen empirical studies met the inclusion criteria. In relation to social stigma in rating their own beliefs and behavioural intentions, youth who did not have TS showed an unfavourable attitude towards individuals with TS in comparison to typically developing peers. Meanwhile, in their own narratives about their lives, young people with TS themselves described some form of devaluation from others as a response to their disorder. Self-degrading comments were denoted in a number of studies in which the children pointed out stereotypical views that they had adopted about themselves. Finally, as regards courtesy stigma, parents expressed guilt in relation to their children’s condition and social alienation as a result of the disorder. Surprisingly, however, there is not one study that focuses primarily on stigma in relation to TS and further studies that examine the subject from the perspective of both the ‘stigmatiser’ and the recipient of stigma are warranted.