Alterations in the cortical dopamine system and microglial activation have been implicated in the pathophysiology of attention-deficit/hyperactivity disorder (ADHD), one of neurodevelopmental ...disorders that can be conventionally treated with a dopamine enhancer (methylphenidate) albeit unsatisfactorily. Here, we investigated the contributions of the dopamine D1 receptor (D1R) and activated microglia and their interactions to the clinical severities in ADHD individuals using positron emission tomography (PET). Twenty-four psychotropic-naïve ADHD individuals and 24 age- and sex-matched typically developing (TD) subjects underwent PET measurements with
CSCH23390 for the D1R and
C(R)PK11195 for activated microglia as well as assessments of clinical symptoms and cognitive functions. The ADHD individuals showed decreased D1R in the anterior cingulate cortex (ACC) and increased activated microglia in the dorsolateral prefrontal cortex (DLPFC) and orbitofrontal cortex (OFC) compared with the TD subjects. The decreased D1R in the ACC was associated with severe hyperactivity in the participants with ADHD. Microglial activation in the DLPFC were associated with deficits in processing speed and attentional ability, and that in the OFC was correlated with lower processing speed in the ADHD individuals. Furthermore, positive correlations between the D1R and activated microglia in both the DLPFC and the OFC were found to be significantly specific to the ADHD group and not to the TD group. The current findings suggest that microglial activation and the D1R reduction as well as their aberrant interactions underpin the neurophysiological mechanism of ADHD and indicate these biomolecular changes as a novel therapeutic target.
It has been recently suggested that contact with nature improves mood via reducing the activity of the prefrontal cortex. However, the specific regions within the prefrontal cortex that underlie this ...effect remain unclear. In this study, we aimed to identify the specific regions involved in the mood-improving effect of viewing images of nature using a 52-channel functional near-infrared spectroscopy (fNIRS). Specifically, we focused on the orbitofrontal cortex (OFC) and dorsolateral prefrontal cortex (dlPFC), two regions associated with affective processing and control. In a randomized controlled crossover experiment, we assigned thirty young adults to view images of nature and built environments for three minutes each in a counterbalanced order. During image viewing, participants wore a fNIRS probe cap and had their oxyhemoglobin (oxy-Hb) measured. Immediately following each image viewing, participants indicated their mood in terms of comfortableness, relaxation, and vigor. Results showed that viewing images of nature significantly increased comfortableness and relaxation but not vigor compared to viewing images of built environments, with a large effect size. Meanwhile, the concentration of oxy-Hb in only the right OFC and none of the other regions significantly decreased while viewing the images of nature compared to built environments, with a medium effect size. We speculate that viewing images of nature improves mood by reducing the activity of or calming the OFC. Since the OFC is hyperactive in patients with depression and anxiety at rest, contact with nature might have therapeutic effects for them.
Recent studies show that even a brief bout of aerobic exercise may enhance creative thinking. However, few studies have investigated the effect of exercise conducted in natural settings. Here, in a ...crossover randomized controlled trial, we investigated the effect of a common daily activity, stair-climbing, on creative thinking. As experimental intervention, subjects were asked to walk downstairs from the fourth to the first floor and back at their usual pace. As control intervention, they walked the same path but using the elevator instead. Compared to using the elevator, stair-climbing enhanced subsequent divergent but not convergent thinking in that it increased originality on the Alternate Use Test (
= 0.486). Subjects on average generated 61% more original uses after stair-climbing. This is the first study to investigate the effect of stair-climbing on creative thinking. Our findings suggest that stair-climbing may be a useful strategy for enhancing divergent thinking in everyday life.
Abundant evidence shows that various forms of physical exercise, even conducted briefly, may improve cognitive functions. However, the effect of physical exercise on creative thinking remains ...under-investigated, and the role of mood in this effect remains unclear. In the present study, we set out to investigate the effect of an acute bout of aerobic exercise on divergent and convergent thinking and whether this effect depends on the post-exercise mood. Forty healthy young adults were randomly assigned to receive a 15-min exercise or control intervention, before and after which they conducted an alternate use test measuring divergent thinking and an insight problem-solving task measuring convergent thinking. It was found that exercise enhanced divergent thinking in that it increased flexibility and fluency. Importantly, these effects were not mediated by the post-exercise mood in terms of pleasure and vigor. In contrast, the effect on convergent thinking depended on subjects' mood after exercise: subjects reporting high vigor tended to solve more insight problems that were unsolved previously, while those reporting low vigor became less capable of solving previously unsolved problems. These findings suggest that aerobic exercise may affect both divergent and convergent thinking, with the former being mood-independent and the latter mood-dependent. If these findings can be replicated with more rigorous studies, engaging in a bout of mood, particularly vigor-enhancing aerobic exercise, may be considered a useful strategy for gaining insights into previously unsolved problems.
Cells respond to DNA damage by activating alternate signaling pathways that induce proliferation arrest or apoptosis. The correct balance between these two pathways is important for maintaining ...genomic integrity and preventing unnecessary cell death. The mechanism by which DNA-damaged cells escape from apoptosis during DNA repair is poorly understood. We show that the DNA replication-initiating kinase Cdc7 actively prevents unnecessary death in DNA-damaged cells. In response to mild DNA damage, Tob levels increase through both a transcriptional mechanism and protein stabilization, resulting in inhibition of pro-apoptotic signaling. Cells lacking Cdc7 expression undergo apoptosis after mild DNA damage, where Cul4-DDB1Cdt2 induces Tob ubiquitination and subsequent degradation. Cdc7 phosphorylates and interacts with Tob to inhibit the Cul4-DDB1Cdt2-dependent Tob degradation. Thus, Cdc7 defines an essential pro-survival signaling pathway by contributing to stabilization of Tob, thereby the viability of DNA-damaged cells being maintained.
Background: Preventing unnecessary cell death is essential for DNA-damaged cells to carry out the DNA repair process.
Results: Cdc7 inhibits the Cul4-DDB1Cdt2-dependent Tob degradation.
Conclusion: Cdc7 enables mild DNA-damaged cells to keep their viability by competing with the Tob degradation system.
Significance: Cells deal with moderate DNA damage not only by cessation of the cell cycle but also through direct mediated pro-survival signaling.
The neocortex and the hippocampus comprise several specific layers containing distinct neurons that originate from progenitors at specific development times, under the control of an adequate ...cell-division patterning mechanism. Although many molecules are known to regulate this cell-division patterning process, its details are not well understood. Here, we show that, in the developing cerebral cortex, the RP58 transcription repressor protein was expressed both in postmitotic glutamatergic projection neurons and in their progenitor cells, but not in GABAergic interneurons. Targeted deletion of the RP58 gene led to dysplasia of the neocortex and of the hippocampus, reduction of the number of mature cortical neurons, and defects of laminar organization, which reflect abnormal neuronal migration within the cortical plate. We demonstrate an impairment of the cell-division patterning during the late embryonic stage and an enhancement of apoptosis of the postmitotic neurons in the RP58-deficient cortex. These results suggest that RP58 controls cell division of progenitor cells and regulates the survival of postmitotic cortical neurons.
We report the absorption of a diffusive spin current in a bulk-carrier compensated topological insulator: Sn0.02−Bi1.08Sb0.9Te2S (Sn-BSTS). By injecting spins into a Sn-BSTS crystal from a ...ferromagnetic metal using spin pumping, we found that the magnetic damping of the ferromagnetic layer is enhanced due to the absorption of the spin current in the surface and bulk states of the topological insulator. We found that the damping enhancement depends critically on temperature, which allows us to disentangle the spin absorption in the surface and bulk states, owing to the nearly perfect carrier compensation in the bulk part at low temperature. Our results show that the absorption of the spin current is dominated by the surface state of the Sn-BSTS crystal at low temperature, whereas the spin absorption in the surface state is comparable to that in the bulk state near room temperature. The coexistence of the spin absorption in the surface and bulk states has been demonstrated in two different systems, where the surface state is coupled with the dynamical magnetization through the diffusive spin current or exchange coupling. These results will be essential for quantitative understanding of the spin absorption and spin-charge conversion due to the spin-momentum locked surface state of topological insulators.
Gynecologic diseases such as uterine fibroids, endometriosis, and adenomyosis are common in women of reproductive age. Case reports and small case series have reported ischemic stroke in women with ...such common noncancerous gynecologic diseases, and their cause of stroke is frequently attributed to cryptogenic stroke or unconventional mechanisms related to hypercoagulability. However, stroke etiology and prognosis are not well known. We assessed the prevalence of and stroke mechanisms related to common noncancerous gynecologic diseases using hospital-based clinical data.
We retrospectively identified consecutive female patients with common noncancerous gynecologic diseases (uterine fibroids, endometriosis, and adenomyosis) diagnosed with ischemic stroke/transient ischemic attack (TIA) between the ages of 20 and 59 years admitted to 10 stroke centers in Japan by reviewing prospectively collected data between 2017 and 2019. The clinical, laboratory, and neuroimaging features were evaluated and compared between patients with conventional stroke mechanisms (CSMs) (large artery atherosclerosis, small vessel occlusion, cardioembolism, and other determined etiology) and non-CSMs (cryptogenic stroke and causes related to hypercoagulability such as nonbacterial thrombotic endocarditis and paradoxical embolism) according to the Trial of Org 10172 in Acute Stroke Treatment criteria.
Of the 470 female patients with ischemic stroke/TIA, 39 (8%) (37 ischemic stroke and 2 TIA) had common noncancerous gynecologic diseases. The most common gynecologic diseases were uterine fibroids in 24 (62%) patients, followed by endometriosis in 9 (23%) and adenomyosis in 6 (15%). Twenty patients (51%) were assigned to the non-CSMs group, and 19 patients (49%) were assigned to the CSMs group. Adenomyosis and endometriosis were more frequent in the non-CSMs group than in the CSMs group. CA125 and D-dimer levels were higher in the non-CSMs group than in the CSMs group. Multiple vascular territory infarcts were frequent in patients with adenomyosis (60%) and endometriosis (43%) in the non-CSMs group. No stroke recurrence or death was observed within 3 months after discharge in both the CSMs and non-CSMs groups. Outcomes at 3 months after discharge were similar in both groups.
In patients with common noncancerous gynecologic diseases, hypercoagulopathy may play a role in the pathogenesis of ischemic stroke/TIA without CSMs.
Keishibukuryogan (KBG; Guizhi-Fuling-Wan in Chinese) is one of the Kampo (Japanese traditional) medicines used to treat patients with climacteric syndrome. KBG can be used by patients who cannot ...undergo hormone replacement therapy due to a history of breast cancer. We evaluated whether cytosine-adenine (CA) repeat polymorphism of the estrogen receptor β gene can be a predictor of the beneficial effect of KBG on climacteric syndrome. We also investigated the relationship between CA repeat polymorphism, the patients’ profiles, and the therapeutic effect. We found that CA was an SS, SL, or LL genotype according to the number of repeats. We studied 39 consecutive patients with climacteric disorders who took KBG for 12 weeks. The diagnosis of climacteric disorders was made on the basis of the Kupperman index. KBG significantly improved the patients’ climacteric symptoms (i.e., vasomotor symptoms in the patients with the LL genotype and melancholia in the patients with the SL genotype). No relationship between the patients’ profiles and CA repeat polymorphism was recognized. CA repeat polymorphism could thus be a potential biomarker to predict the efficacy of KBG in climacteric syndrome, and its use will help to reduce the cost of treating this syndrome by focusing the administration of KBG on those most likely to benefit from it.
PDF
