Glia transmit negative valence information during aversive learning in Drosophila.

During Drosophila aversive olfactory conditioning, aversive shock information needs to be transmitted to the mushroom bodies (MBs) to associate with odor information. We report that aversive information is transmitted by ensheathing glia (EG) that surround the MBs. Shock induces vesicular exocytosis of glutamate from EG. Blocking exocytosis impairs aversive learning, whereas activation of EG can replace aversive stimuli during conditioning. Glutamate released from EG binds to N-methyl-d-aspartate receptors in the MBs, but because of Mg2+ block, Ca2+ influx occurs only when flies are simultaneously exposed to an odor. Vesicular exocytosis from EG also induces shock-associated dopamine release, which plays a role in preventing formation of inappropriate associations. These results demonstrate that vesicular glutamate released from EG transmits negative valence information required for associative learning.

Hepatic phosphatidylcholine catabolism driven by PNPLA7 and PNPLA8 supplies endogenous choline to replenish the methionine cycle with methyl groups.

Choline supplies methyl groups for regeneration of methionine and the methyl donor S-adenosylmethionine in the liver. Here, we report that the catabolism of membrane phosphatidylcholine (PC) into water-soluble glycerophosphocholine (GPC) by the phospholipase/lysophospholipase PNPLA8-PNPLA7 axis enables endogenous choline stored in hepatic PC to be utilized in methyl metabolism. PNPLA7-deficient mice show marked decreases in hepatic GPC, choline, and several metabolites related to the methionine cycle, accompanied by various signs of methionine insufficiency, including growth retardation, hypoglycemia, hypolipidemia, increased energy consumption, reduced adiposity, increased fibroblast growth factor 21 (FGF21), and an altered histone/DNA methylation landscape. Moreover, PNPLA8-deficient mice recapitulate most of these phenotypes. In contrast to wild-type mice fed a methionine/choline-deficient diet, both knockout strains display decreased hepatic triglyceride, likely via reductions of lipogenesis and GPC-derived glycerol flux. Collectively, our findings highlight the biological importance of phospholipid catabolism driven by PNPLA8/PNPLA7 in methyl group flux and triglyceride synthesis in the liver.

Parallel gold enhancement of quantum dots 565/655 for double-labelling correlative light and electron microscopy on human autopsied samples.

Cadmium selenide quantum dots (QDs) are fluorescent and electron-dense nanoparticles. When used as reporter of immunolabeling, this dual visibility is essential for direct comparison of its fluorescent signals on light microscopy (LM) and their ultrastructrual counterparts on electron microscopy (EM) as correlative light and electron microscopy (CLEM). To facilitate EM recognition, QDs on EM grid were gold enhanced, which increased their size and electron density. On histological sections as well, gold-enhanced QDs, used as a reporter of immunolabeling, were easily recognized on EM. Because target structures are visible on bright field microscopy, gold enhancement facilitated trimming the target structures into final EM sections. Furthermore, gold enhancement of rod-shaped QD655 on EM grid was accentuated on their tips while spherical QD565 was gold-enhanced as sphere in contrast. This EM distinction was evident on histological sections where QD565 (green fluorescence) and QD655 (red fluorescence) were used as a reporter pair for double immunolabeling. Double-labeled immuno-fluorescent images, initially captured before EM processing, are now compared with their respective immuno EM counterparts. Specific labeling of each epitope was corroborated by mutual comparison between LM and EM. Although fluoronanogold may be a candidate reporter partner with QDs for gold-enhanced, double-labeling CLEM, its limited penetration into fixed tissue hampers universal use for thick histological sections. Gold-enhancement of QD immunolabeling, now expanded to double-labeling CLEM for human brain samples, will pave the way to translate molecular events into ultrastructural morphopathogenesis in situ.

Effect of subjective vertical perception on lateral flexion posture of patients with Parkinson's disease.

In a retrospective study we tested our hypothesis that the subjective postural vertical ratio (SPV ratio), i.e., the subjective postural vertical measured in relation to the lateral flexion axis, is predictive of lateral trunk flexion in patients with Parkinson's disease (PD). Twenty-five patients were included. The SPV angle, i.e., the subjective perception of a vertical position with reference to the vertical axis, and the SPV ratio, i.e., the SPV angle with reference to the axis of lateral flexion, were calculated. The SPV ratio (r = 0.698, P = 0.001) and LTF angle (r = - 0.601, P = 0.001) correlated with change in the LTF angle at 1 year. The SPV ratio was significantly smaller in patients for whom lateral trunk flexion improved (n = 12) than in those for whom it did not improve (n = 13) (0.99 ± 0.78 vs 1.66 ± 0.71, P = 0.011). The AUC under the ROC curve of the SPV ratio for discrimination of improvement was 0.795 (95% confidence interval: 0.61-0.98). We found that the SPV ratio is associated with change in the LTF and that it can conceivably be used to predict the likelihood of improvement in PD-associated lateral trunk flexion.

Subjective postural vertical in Parkinson's disease with lateral trunk flexion.

BACKGROUND: Patients with Parkinson's disease (PD) and associated lateral trunk flexion (LTF) cannot accurately perceive their own verticality. OBJECTIVE: We measured the subjective postural vertical in coronal plane (SPVc) angle on patients' ipsilateral and contralateral sides and combined to clarify the effects of SPVc on LTF. We also investigated effects of the SPVc angle on LTF severity. METHODS: Thirty-nine patients (aged 74.1 ± 7.6 years) were divided between those with mild LTF (LTF angle < 10°, n = 34) and those with moderate to severe LTF (LTF angle ≥ 10°, n = 5) for comparison of the LTF angle, SPVc angle on both sides, inter-measurement variation in the SPVc angle, and the LTF to SPVc angle ratio (SPVc ratio). RESULTS: We found significant positive correlation between LTF and the SPVc angle on the combined (r = .54, P = .001), ipsilateral (r = .51, P = .002), and contralateral (r = .50, P = .002) sides. We found significant negative correlation between the LTF angle and the SPVc ratio on the combined SPVc (r = -.82, P = .001), ipsilateral (r = -.69, P = .001), and contralateral (r = -.75, P = .001) sides and between the LTF and ipsilateral side coefficient of variation (r = -.34, P = .038). SPVc angles on ipsilateral and contralateral sides were significantly greater in cases of moderate to severe LTF than in cases of mild LTF (P < .01). CONCLUSIONS: Subjective postural vertical in coronal plane assessment may be useful for assessing patients with PD and associated LTF.

Correction: Motor planning error in Parkinson's disease and its clinical correlates.

[This corrects the article DOI: 10.1371/journal.pone.0202228.].

Deterioration of postural deformity in Parkinson's disease patients with punding and hobbyism.

This study aimed to examine whether worsening of postural deformities is seen in Parkinson's disease (PD) patients who exhibit the behavioral disorders punding or hobbyism (P-H), which involve maintaining the same poor posture. The subjects were 80 patients with PD (aged 73.1 ±â€¯8.8 years; duration of disease, 6.4 ±â€¯5.5 years). Using the Japanese-language version of the Questionnaire for Impulsive-Compulsive Disorders in Parkinson's Disease (J-QUIP), a group with P-H alone (P-H only group) and a group without impulsive-compulsive behaviors (non-ICB group) were compared with respect to the angles of forward and lateral trunk flexion while standing at rest. The group with ICBs (ICB group) identified by the J-QUIP consisted of 36 patients (45.0%). Of these, 25 (31.3%) were in the P-H only group. The non-ICB group, who were negative on all items of the J-QUIP, consisted of 44 patients (55.0%). Significantly higher values were seen in the P-H only group compared with non-ICB group for the angle of forward flexion of the trunk (FFT angle, p = 0.04), Unified Parkinson's Disease Rating Scale (UPDRS) part II score (p = 0.002), and UPDRS total score (p = 0.007). The FFT angle was increased and activities of daily living decreased in PD patients with P-H.

Subjective Vertical Position Allows Prediction of Postural Deterioration in Patients with Parkinson's Disease.

BACKGROUND: We believe that, in patients with Parkinson's disease (PD), a forward-directed increase in the subjective vertical position (SV) leads to prolonged worsening of forward flexion of the trunk (FFT) mainly because the body adjusts to the SV. We conducted a study to clarify the relation between the SV angle, FFT angle, and various other clinical measures by comparing baseline values against values obtained 1 year later. METHODS: A total of 39 PD patients (mean age, 71.9 ± 10.1 years; disease duration, 7.2 ± 5.4 years; modified Hoehn & Yahr (mH&Y) score, 2.6 ± 0.7) were enrolled. The Unified Parkinson's Disease Rating Scale score, Mini-Mental State Examination (MMSE) score, mH&Y score, FFT angle, SV angle, and levodopa-equivalent dose (LED) were assessed at the time of enrollment (baseline evaluation) and 1 year later. RESULTS: Eighteen patients (46%) complied with the protocol and completed the study. Significant increases were observed in the 1-year SV angle (p=0.02), MMSE score (p=0.008), and LED (p=0.001) compared to baseline values. Correlation was observed between the baseline SV angle and baseline and 1-year FFT angles (r=0.64, p=0.008 and r=0.58, p=0.012, respectively) and between the 1-year SV angle and 1-year FFT angle (r=0.63, p=0.005). CONCLUSION: Our data suggest that the SV contributes to increased FFT.

Motor planning error in Parkinson's disease and its clinical correlates.

This study aimed to investigate (a) motor planning difficulty by using a two-step test in Parkinson's disease (PD) compared with age-matched healthy subjects and (b) the relationship between motor planning difficulty and clinical factors. The two-step test was performed by 58 patients with PD with Hoehn & Yahr (H&Y) stage I-IV and 110 age-matched healthy older adult controls. In the two-step test, the participants estimated the two-step distance with maximum effort. Subsequently, they performed the actual two-step trial to measure the actual maximum distance. We calculated the accuracy of the estimation (estimated distance minus actual distance). In both groups, subjects who estimated >5 cm were defined as the overestimation group, and those who estimated <5 cm over- and underestimation were defined as the non-overestimation group. The overestimation group consisted of 17 healthy older adults (15.5%) and 23 patients with PD (39.7%). The number of patients with PD with overestimation was significantly more than that of healthy controls by Chi-squared test. H&Y stage and the Unified Parkinson's Disease Rating Scale (UPDRS) part II and III scores in overestimation group in PD patients were significantly higher than those in overestimation group in PD patients. Moreover, multiple regression using H&Y stage and UPDRS parts II and III as independent variables showed that the UPDRS part II score was the only related factor for the estimation error distance. Estimation error distance was significant correlated with UPDRS parts II and III. Patients with PD easily have higher rates of motor-related overestimation than age-matched healthy controls. In addition, UPDRS parts II and III expressed ability of activities of daily living and motor function as influences on motor-related overestimation. Particularly, multiple regression indicated that UPDRS part II directly showed the ability of daily living as an essential factor for overestimation.

Forward flexion of trunk in Parkinson's disease patients is affected by subjective vertical position.

PURPOSE: No method has been established to evaluate the dissociation between subjective and objective vertical positions with respect to the self-awareness of postural deformity in patients with Parkinson's disease (PD). The purpose of this study was to demonstrate, from the relationship between an assessment of the dissociation of subjective and objective vertical positions of PD patients and an assessment based on established PD clinical evaluation scales, that the dissociation regarding vertical position is a factor in the severity of the forward flexion of trunk (FFT). METHODS: Subjects were 39 PD patients and 15 age-matched healthy individuals (control group). Posture was evaluated with measurement of FFT angle during static standing and the subjective vertical position (SV) of the patient. For evaluation of motor function, the Modified Hoehn & Yahr scale, Unified Parkinson's Disease Rating Scale (UPDRS), 3-m Timed Up and Go Test (TUG), and Functional Reach Test (FRT) were used. RESULTS: In PD patients, FFT angle in the 3rd tertile of patients was 13.8±9.7°, significantly greater than those in the control group and the 1st and 2nd tertiles of PD patients (control group vs 3rd tertile, p = 0.008; 1st tertile vs 3rd tertile, p<0.001; 2nd vs 3rd tertile, p = 0.008). In multiple regression analysis for factors in the FFT angle, significant factors were SV, disease duration, and the standard deviation of each SV angle measurement. CONCLUSION: The dissociation between SV and objective vertical position affects the FFT of PD patients, suggesting an involvement of non-basal ganglia pathologies.

Social interaction influences blood cortisol values and brain aromatase genes in the protandrous false clown anemonefish, Amphiprion ocellaris.

Anemonefish, Amphiprion spp., are socially controlled, protandrous sex changers with a monogamous mating system. Under certain conditions, sexually immature anemonefish with ambisexual gonads differentiate directly into males or females. Formation and maintenance of social rank in a group are considered key requirements for the induction of sex change or differentiation. Generally, each animal living in a social group experiences a different level of social stress in accordance with its social rank, and we hypothesize that the stress situation of individual anemonefish influences its sex determination. Groups of three sexually immature anemonefish were placed into each of five experimental tanks and kept for 10 days to allow for social rank formation and behavioral observation. The fish were then euthanized, and blood and brain samples were collected from each fish. The social rank of each individual was distinguishable from day 1 of the experiment. Aggressive behaviors were most frequent and blood Cortisol values were higher in dominant individuals. The transcription of mRNA for stress-related genes, i.e., those encoding for glucocorticoid and arginine vasotocin receptors, was higher in the brains of dominant individuals than in other social ranks. Furthermore, we detected higher transcription levels of gonad and brain aromatase genes, which encode the enzyme that converts androgens into estrogens, in the brains of dominant individuals. These results suggest that social rank reflects the blood Cortisol value, which in turn leads to sex differentiation by manipulating transcription of genes, including aromatase genes, in the brain.