Quantitative Threshold Determination of Auditory Brainstem Responses in Mouse Models

The auditory brainstem response (ABR) is a scalp recording of potentials produced by sound stimulation, and is commonly used as an indicator of auditory function. However, the ABR threshold, which is the lowest audible sound pressure, cannot be objectively determined since it is determined visually using a measurer, and this has been a problem for several decades. Although various algorithms have been developed to objectively determine ABR thresholds, they remain lacking in terms of accuracy, efficiency, and convenience. Accordingly, we proposed an improved algorithm based on the mutual covariance at adjacent sound pressure levels. An ideal ABR waveform with clearly defined waves I–V was created; moreover, using this waveform as a standard template, the experimentally obtained ABR waveform was inspected for disturbances based on mutual covariance. The ABR testing was repeated if the value was below the established cross-covariance reference value. Our proposed method allowed more efficient objective determination of ABR thresholds and a smaller burden on experimental animals.Tanaka K., Ohara S., Matsuzaka T., et al. Quantitative Threshold Determination of Auditory Brainstem Responses in Mouse Models. International Journal of Molecular Sciences 24, 11393 (2023); https://doi.org/10.3390/ijms241411393

Association of cognitive performance with interleukin-6 receptor Asp358Ala polymorphism in healthy adults

Wechsler adult intelligence scale-revised was performed in 576 healthy adults to examine whether a functional polymorphism (Asp358Ala) of the IL-6 receptor (IL-6R) gene is associated with cognitive performance. Verbal intelligence quotient in Asp homozygotes was significantly higher compared to Ala carriers (P = 0.005). Compared to Ala carriers, Asp homozygotes performed better in the verbal subtests requiring long-term memory stores. Elevated IL-6 and soluble IL-6R levels in Ala carriers may have negative impact on acquiring verbal cognitive ability requiring long-term memory.ArticleJOURNAL OF NEURAL TRANSMISSION. 119(3):313-318 (2012)journal articl

Association of interleukin-1 beta genetic polymorphisms with cognitive performance in elderly females without dementia

Interleukin-1 beta (IL-1 beta) is considered to have a role in age-related cognitive decline. A recent study has shown that a promoter polymorphism of the IL-1 beta gene (rs16944) is associated with cognitive performance in elderly males without dementia. In this study, we examined whether polymorphisms of the IL-1 beta gene also influence cognitive functions in elderly females. Cognitive functions were assessed by the Wechsler adult intelligence scale-revised (WAIS-R) in 99 elderly (>= 60 years) females without dementia. We selected five tagging polymorphisms from the IL-1 beta gene and examined the associations with the WAIS-R scores. Significant associations were found between verbal intelligence quotient (IQ) and the genotypes of rs1143634 and rs1143633 (P = 0.0037 and P = 0.010, respectively). No significant associations of rs16944 genotype were found with verbal or performance IQ. However, individuals homozygous for the G allele of rs16944 achieved higher scores in digit span compared with their counterpart, which is consistent with the previous findings in males. These results suggest that IL-1 beta gene variation may have a role in cognitive functions in aging females as well as males. Journal of Human Genetics (2011) 56, 613-616; doi:10.1038/jhg.2011.56; published online 26 May 2011ArticleJOURNAL OF HUMAN GENETICS. 56(8):613-616 (2011)journal articl

More severe impairment of manual dexterity in bipolar disorder compared to unipolar major depression

Background: Mood disorders are associated with various neurocognitive deficits. However, few studies have reported the impairment of motor dexterity in unipolar depression and bipolar disorder. In the present study, manual dexterity was compared between unipolar major depression, bipolar disorder, and healthy controls. Methods: Manual dexterity was assessed by the Purdue pegboard test in 98 patients with unipolar major depression, 48 euthymic or depressed patients with bipolar disorder, and 158 healthy controls, matched for age and gender. Results: Compared to healthy controls, sum of the scores of right, left, and both hands subtests (R + L+ B) was significantly lower in both patients with unipolar depression and bipolar disorder (P= 0.0034 and P<0.0001, respectively). Furthermore, R + L + B was significantly lower in bipolar disorder compared to unipolar depression (P=0.0016). Lithium dose and chlorpromazine equivalent dose of antipsychotics were significantly negatively correlated with some of the subtest scores. On the other hand, depression severity did not significantly correlate with any of the subtest scores. Difference in R + L+ B between unipolar depression and bipolar disorder remained statistically significant even after controlling for gender, age, lithium dose, and chlorpromazine equivalent dose (P = 0.0028). Limitations Bipolar patients during manic episode were not included in the study. Conclusions: Gross movement dexterity was impaired in both patients with unipolar depression and bipolar disorder. The severity of impairment was significantly greater in patients with bipolar disorder. The functional difference between unipolar and bipolar patients may suggest different pathological conditions between the two depressive disorders.ArticleJOURNAL OF AFFECTIVE DISORDERS. 136(3):1047-1052 (2012)journal articl

Effects of long-term cigarette smoke exposure on bone metabolism, structure, and quality in a mouse model of emphysema

Smoking is a common risk factor for both chronic obstructive pulmonary disease (COPD) and osteoporosis. In patients with COPD, severe emphysema is a risk factor for vertebral fracture; however, the effects of smoking or emphysema on bone health remain largely unknown. We report bone deterioration in a mouse model of emphysema induced by nose-only cigarette smoke (CS) exposure. Unexpectedly, short-term exposure for 4-weeks decreased bone turnover and increased bone volume in mice. However, prolonged exposure for 20- and 40-weeks reversed the effects from suppression to promotion of bone resorption. This long-term CS exposure increased osteoclast number and impaired bone growth, while it increased bone volume. Strikingly, long-term CS exposure deteriorated bone quality of the lumbar vertebrae as illustrated by disorientation of collagen fibers and the biological apatite c-axis. This animal model may provide a better understanding of the mechanisms underlying the deterioration of bone quality in pulmonary emphysema caused by smoking.Effects of long-term cigarette smoke exposure on bone metabolism, structure, and quality in a mouse model of emphysema. Mamoru Sasaki et al. PLOS ONE. 2018. 1(30) doi.org/10.1371/journal.pone.019161

Hypermineralization of Hearing-Related Bones by a Specific Osteoblast Subtype

Auditory ossicles in the middle ear and bony labyrinth of the inner ear are highly mineralized in adult mammals. Cellular mechanisms underlying formation of dense bone during development are unknown. Here, we found that osteoblast-like cells synthesizing highly mineralized hearing-related bones produce both type I and type II collagens as the bone matrix, while conventional osteoblasts and chondrocytes primarily produce type I and type II collagens, respectively. Furthermore, these osteoblast-like cells were not labeled in a “conventional osteoblast”-specific green fluorescent protein (GFP) mouse line. Type II collagen-producing osteoblast-like cells were not chondrocytes as they express osteocalcin, localize along alizarin-labeled osteoid, and form osteocyte lacunae and canaliculi, as do conventional osteoblasts. Auditory ossicles and the bony labyrinth exhibit not only higher bone matrix mineralization but also a higher degree of apatite orientation than do long bones. Therefore, we conclude that these type II collagen-producing hypermineralizing osteoblasts (termed here auditory osteoblasts) represent a new osteoblast subtype. © 2021 The Authors. Journal of Bone and Mineral Research published by Wiley Periodicals LLC on behalf of American Society for Bone and Mineral Research (ASBMR).Kuroda Y., Kawaai K., Hatano N., et al. Hypermineralization of Hearing-Related Bones by a Specific Osteoblast Subtype. Journal of Bone and Mineral Research, 36, 8, 1535. https://doi.org/10.1002/jbmr.4320

Diagnostic specificity of the child psychosis-risk screening system with a focus on the differentiation of schizophrenia spectrum disorders and neurodevelopmental disorders

BackgroundResearch on early psychosis has begun to identify psychiatric characteristics of the prodromal period of schizophrenia; however, subclinical characteristics of children in non-psychiatric fields have not been fully investigated. In our previous study, we developed the Child Psychosis-risk Screening System (CPSS).ObjectiveIn the present cross-sectional study, we attempted to identify the risk of developing psychosis in pediatric (n = 216) and psychiatric outpatients (n = 120), aged 6– 18 years, with the CPSS.MethodsAn analysis of variance of CPSS risk was performed in six diagnostic categories to examine specificity for each diagnosis. Receiver operating characteristic (ROC) curve analysis was conducted using the onset of schizophrenia spectrum as the outcome, and the discriminatory power and cut off values of the CPSS were determined. Logistic regression analysis was performed using clinical data to identify factors associated with the risk group (those at high risk of developing psychosis in the future) identified using the CPSS.ResultsThere were significant differences in risk variance among diagnostic categories (p &lt; 0.001), especially between schizophrenia spectrum disorders (SSD) and neurodevelopmental disorders (p = 0.001). CPSS had sufficient discriminatory power for SSD diagnosis [area under the ROC curve = 0.853 (95% confidence interval: 0.774–0.931)]. The cut off value for the risk of SSD was determined to be 98.1%, achieving the best mean of the sum of sensitivity (90.9%) and specificity (84.0%). Cross-sectional logistic regression analysis showed that along with “SSD diagnosis,” “winter birth,” and “maltreatment” were factors associated with the risk group (odds ratio = 38.05 [p = 0.001], 2.30 [p = 0.016], and 0.12 [p = 0.024], respectively).ConclusionCPSS may have potential use in the early detection of psychosis and differentiation from neurodevelopmental disorders, but this study was small and further studies with larger sample sizes and longitudinal study designs are required prior to its use in routine clinical practice