METHODS: Slitrk1-KD mice were induced by bilaterally injecting Slitrk1 siRNA into their dorsal striatum. Control mice received scrambled siRNA injection. Their TS-like tic behaviors, prepulse inhibition, sensory-motor function and dopamine-related behaviors were compared. We also compared dopamine and ACh levels in microdialysates, Slitrk protein and dopamine transporter levels, and numbers of Slitrk-positive ChIs and activated ChIs in the striatum between two mouse groups, and electrophysiological properties between Slitrk-positive and Slitrk-negative striatal ChIs.
RESULTS: Slitrk1-KD mice exhibit TS-like haloperidol-sensitive stereotypic tic behaviors, impaired prepulse inhibition, and delayed sensorimotor response compared with the control group. These TS-like characteristics correlate with lower striatal Slitrk1 protein levels, fewer Slitrk1-containing ChIs, and fewer activated ChIs in Slitrk1-KD mice. Based on their electrophysiological properties, Slitrk1-negative ChIs are less excitable than Slitrk1-positive ChIs. Slitrk1-KD mice have lower evoked acetylcholine and dopamine levels, higher tonic dopamine levels, and downregulated dopamine transporters in the striatum, increased apomorphine-induced climbing behaviors, and impaired methamphetamine-induced hyperlocomotion compared with controls.
INTERPRETATION: Slitrk1 is pivotal in maintaining striatal ChIs activity and subsequent dopaminergic transmission for normal motor functioning. Furthermore, conditional striatal Slitrk1-KD mice may serve as a translational modality with aspects of TS phenomenology. ANN NEUROL 2023.
OBJECTIVES: To evaluate fatigue, identify factors associated with fatigue and assess the effect of fatigue on health-related quality of life (HRQoL) in a multi-ethnic cohort of RA patients.
METHODS: A cross-sectional study was performed in patients who fulfilled European League Against Rheumatism/ American College of Rheumatology 2010 criteria for RA. Functional Assessment of Chronic Illness Therapy - Fatigue (FACIT-F) questionnaire was used to assess fatigue. Potential factors for fatigue were categorized into RA-related (gender, seropositivity [rheumatoid factor and/or anti-citrullinated protein antibody], disease duration, visual analog scale pain score, Disease Activity Score of 28 joints - erythrocyte sedimentation rate [DAS28-ESR], ESR, hemoglobin level, functional disability [Health Assessment Questionnaire - Disability Index, HAQ-DI score], EQ-5D-3L, concomitant prednisolone use and number of conventional synthetic disease-modifying anti-rheumatic drugs [csDMARDs] used) and non-RA-related (age, body mass index, ethnicity and number of co-morbidities).
RESULTS: A total of 214 patients (86.9% female) were included; the median age was 62 (25-91) years and 67.3% were seropositive. Seventy-six (33.5%) patients had moderate disease activity, 12 (5.6%) had high disease activity and 152 (71%) patients had mild difficulties to moderate disability HAQ-DI scores. Median of total FACIT-F score was 113.2 (36.3-160.0). Joint factors of younger age, longer disease duration, higher HAQ score (increased functional disability), and lower EQ-5D (poorer HRQoL) were significantly associated with higher levels of fatigue (all P