Dopamine D3 receptor and GSK3ß signaling mediate deficits in novel object recognition memory within dopamine transporter knockdown mice.

BACKGROUND: Over-stimulation of dopamine signaling is thought to underlie the pathophysiology of a list of mental disorders, such as psychosis, mania and attention-deficit/hyperactivity disorder. These disorders are frequently associated with cognitive deficits in attention or learning and memory, suggesting that persistent activation of dopamine signaling may change neural plasticity to induce cognitive or emotional malfunction. METHODS: Dopamine transporter knockdown (DAT-KD) mice were used to mimic a hyper-dopamine state. Novel object recognition (NOR) task was performed to assess the recognition memory. To test the role of dopamine D3 receptor (D3R) on NOR, DAT-KD mice were treated with either a D3R antagonist, FAUC365 or by deletion of D3R. Total or phospho-GSK3 and -ERK1/2 signals in various brain regions were measured by Western blot analyses. To examine the impact of GSK3 signal on NOR, wild-type mice were systemically treated with GSK3 inhibitor SB216763 or, micro-injected with lentiviral shRNA of GSK3ß or GSK3α in the medial prefrontal cortex (mPFC). RESULTS: We confirmed our previous findings that DAT-KD mice displayed a deficit in NOR memory, which could be prevented by deletion of D3R or exposure to FAUC365. In WT mice, p-GSK3α and p-GSK3ß were significantly decreased in the mPFC after exposure to novel objects; however, the DAT-KD mice exhibited no such change in mPFC p-GSK3α/ß levels. DAT-KD mice treated with FAUC365 or with D3R deletion exhibited restored novelty-induced GSK3 dephosphorylation in the mPFC. Moreover, inhibition of GSK3 in WT mice diminished NOR performance and impaired recognition memory. Lentiviral shRNA knockdown of GSK3ß, but not GSK3α, in the mPFC of WT mice also impaired NOR. CONCLUSION: These findings suggest that D3R acts via GSK3ß signaling in the mPFC to play a functional role in NOR memory. In addition, treatment with D3R antagonists may be a reasonable approach for ameliorating cognitive impairments or episodic memory deficits in bipolar disorder patients.

Quantitative transmastoid ultrasound for detecting middle ear effusion in pediatric patients.

BACKGROUND AND OBJECTIVE: Ultrasound has emerged as a promising modality for detecting middle ear effusion (MEE) in pediatric patients. Among different ultrasound techniques, ultrasound mastoid measurement was proposed to allow noninvasive detection of MEE by estimating the Nakagami parameters of backscattered signals to describe the echo amplitude distribution. This study further developed the multiregional-weighted Nakagami parameter (MNP) of the mastoid as a new ultrasound signature for assessing effusion severity and fluid properties in pediatric patients with MEE. METHODS: A total of 197 pediatric patients (n = 133 for the training group; n = 64 for the testing group) underwent multiregional backscattering measurements of the mastoid for estimating MNP values. MEE, the severity of effusion (mild to moderate vs. severe), and the fluid properties (serous and mucous) were confirmed through otoscopy, tympanometry, and grommet surgery and were compared with the ultrasound findings. The diagnostic performance was evaluated using the area under the receiver operating characteristic curve (AUROC). RESULTS: The training dataset revealed significant differences in MNPs between the control and MEE groups, between mild to moderate and severe MEE, and between serous and mucous effusion were observed (p < 0.05). As with the conventional Nakagami parameter, the MNP could be used to detect MEE (AUROC: 0.87; sensitivity: 90.16%; specificity: 75.35%). The MNP could further identify effusion severity (AUROC: 0.88; sensitivity: 73.33%; specificity: 86.87%) and revealed the possibility of characterizing fluid properties (AUROC: 0.68; sensitivity: 62.50%; specificity: 70.00%). The testing results demonstrated that the MNP method enabled MEE detection (AUROC = 0.88, accuracy = 88.28%, sensitivity = 92.59%, specificity = 84.21%), was effective in assessing MEE severity (AUROC = 0.83, accuracy = 77.78%, sensitivity = 66.67%, specificity = 83.33%), and showed potential for characterizing fluid properties of effusion (AUROC = 0.70, accuracy = 72.22%, sensitivity = 62.50%, specificity = 80.00%). CONCLUSIONS: Transmastoid ultrasound combined with the MNP not only leverages the strengths of the conventional Nakagami parameter for MEE diagnosis but also provides a means to assess MEE severity and effusion properties in pediatric patients, thereby offering a comprehensive approach to noninvasive MEE evaluation.

Ultrasound tissue scatterer distribution imaging: An adjunctive diagnostic tool for shear wave elastography in characterizing focal liver lesions.

OBJECTIVES: Focal liver lesion (FLL) is a prevalent finding in cross-sectional imaging, and distinguishing between benign and malignant FLLs is crucial for liver health management. While shear wave elastography (SWE) serves as a conventional quantitative ultrasound tool for evaluating FLLs, ultrasound tissue scatterer distribution imaging (TSI) emerges as a novel technique, employing the Nakagami statistical distribution parameter to estimate backscattered statistics for tissue characterization. In this prospective study, we explored the potential of TSI in characterizing FLLs and evaluated its diagnostic efficacy with that of SWE. METHODS: A total of 235 participants (265 FLLs; the study group) were enrolled to undergo abdominal examinations, which included data acquisition from B-mode, SWE, and raw radiofrequency data for TSI construction. The area under the receiver operating characteristic curve (AUROC) was used to evaluate performance. A dataset of 20 patients (20 FLLs; the validation group) was additionally acquired to further evaluate the efficacy of the TSI cutoff value in FLL characterization. RESULTS: In the study group, our findings revealed that while SWE achieved a success rate of 49.43 % in FLL measurements, TSI boasted a success rate of 100 %. In cases where SWE was effectively implemented, the AUROCs for characterizing FLLs using SWE and TSI stood at 0.84 and 0.83, respectively. For instances where SWE imaging failed, TSI achieved an AUROC of 0.78. Considering all cases, TSI presented an overall AUROC of 0.81. There was no statistically significant difference in AUROC values between TSI and SWE (p > 0.05). In the validation group, using a TSI cutoff value of 0.67, the AUROC for characterizing FLLs was 0.80. CONCLUSIONS: In conclusion, ultrasound TSI holds promise as a supplementary diagnostic tool to SWE for characterizing FLLs.