Synaptic Remodeling Depends on Signaling between Serotonin Receptors and the Extracellular Matrix

Rewiring of synaptic circuitry pertinent to memory formation has been associated with morphological changes in dendritic spines and with extracellular matrix (ECM) remodeling. Here, we mechanistically link these processes by uncovering a signaling pathway involving the serotonin 5-HT7 receptor (5-HT7R), matrix metalloproteinase 9 (MMP-9), the hyaluronan receptor CD44, and the small GTPase Cdc42. We highlight a physical interaction between 5-HT7R and CD44 (identified as an MMP-9 substrate in neurons) and find that 5-HT7R stimulation increases local MMP-9 activity, triggering dendritic spine remodeling, synaptic pruning, and impairment of long-term potentiation (LTP). The underlying molecular machinery involves 5-HT7R-mediated activation of MMP-9, which leads to CD44 cleavage followed by Cdc42 activation. One important physiological consequence of this interaction includes an increase in neuronal outgrowth and elongation of dendritic spines, which might have a positive effect on complex neuronal processes (e.g., reversal learning and neuronal regeneration)

Impact of an injury hospital admission on childhood academic performance: a Welsh population-based data linkage study

Background While injuries can impact on children’s educational achievements (with threats to their development and employment prospects), these risks are poorly quantified. This population-based longitudinal study investigated the impact of an injury-related hospital admission on Welsh children’s academic performance. Methods The Secure Anonymised Information Linkage databank, 55 587 children residing in Wales from 2006 to 2016 who had an injury hospital admission (58.2% males; 16.8% born in most deprived Wales area; 80.1% one injury hospital admission) were linked to data from the Wales Electronic Cohort for Children. The primary outcome was the Core Subject Indicator reflecting educational achievement at key stages 2 (school years 3–6), 3 (school years 7–9) and 4 (school years 10–11). Covariates in models included demographic, birth, injury and school characteristics. Results Educational achievement of children was negatively associated with: pedestrian injuries (adjusted risk ratio, (95% CIs)) (0.87, (0.83 to 0.92)), cyclist (0.96, (0.94 to 0.99)), high fall (0.96, (0.94 to 0.97)), fire/flames/smoke (0.85, (0.73 to 0.99)), cutting/piercing object (0.96, (0.93 to 0.99)), intentional self-harm (0.86, (0.82 to 0.91)), minor traumatic brain injury (0.92, (0.86 to 0.99)), contusion/open wound (0.93, (0.91 to 0.95)), fracture of vertebral column (0.78, (0.64 to 0.95)), fracture of femur (0.88, (0.84 to 0.93)), internal abdomen/pelvic haemorrhage (0.82, (0.69 to 0.97)), superficial injury (0.94, (0.92 to 0.97)), young maternal age (<18 years: 0.91, (0.88 to 0.94); 19–24 years: 0.94, (0.93 to 0.96)); area based socioeconomic status (0.98, (0.97 to 0.98)); moving to a more deprived area (0.95, (0.93 to 0.97)); requiring special educational needs (0.46, (0.44 to 0.47)). Positive associations were: being female (1.04, (1.03 to 1.06)); larger pupil school sizes and maternal age 30+ years. Conclusion This study highlights the importance on a child’s education of preventing injuries and implementing intervention programmes that support injured children. Greater attention is needed on equity-focused educational support and social policies addressing needs of children at risk of underachievement, including those from families experiencing poverty

Blood pressure trajectory of inpatient stroke rehabilitation patients from the Determining Optimal Post-Stroke Exercise (DOSE) trial over the first 12 months post-stroke

BackgroundHigh blood pressure (BP) is the primary risk factor for recurrent strokes. Despite established clinical guidelines, some stroke survivors exhibit uncontrolled BP over the first 12 months post-stroke. Furthermore, research on BP trajectories in stroke survivors admitted to inpatient rehabilitation hospitals is limited. Exercise is recommended to reduce BP after stroke. However, the effect of high repetition gait training at aerobic intensities (&gt;40% heart rate reserve; HRR) during inpatient rehabilitation on BP is unclear. We aimed to determine the effect of an aerobic gait training intervention on BP trajectory over the first 12 months post-stroke.MethodsThis is a secondary analysis of the Determining Optimal Post-Stroke Exercise (DOSE) trial. Participants with stroke admitted to inpatient rehabilitation hospitals were recruited and randomized to usual care (n = 24), DOSE1 (n = 25; &gt;2,000 steps, 40–60% HRR for &gt;30 min/session, 20 sessions over 4 weeks), or DOSE2 (n = 25; additional DOSE1 session/day) groups. Resting BP [systolic (SBP) and diastolic (DBP)] was measured at baseline (inpatient rehabilitation admission), post-intervention (near inpatient discharge), 6- and 12-month post-stroke. Linear mixed-effects models were used to examine the effects of group and time (weeks post-stroke) on SBP, DBP and hypertension (≥140/90 mmHg; ≥130/80 mmHg, if diabetic), controlling for age, stroke type, and baseline history of hypertension.ResultsNo effect of intervention group on SBP, DBP, or hypertension was observed. BP increased from baseline to 12-month post-stroke for SBP (from [mean ± standard deviation] 121.8 ± 15.0 to 131.8 ± 17.8 mmHg) and for DBP (74.4 ± 9.8 to 78.5 ± 10.1 mmHg). The proportion of hypertensive participants increased from 20.8% (n = 15/72) to 32.8% (n = 19/58). These increases in BP were statistically significant: an effect [estimation (95%CI), value of p] of time was observed on SBP [0.19 (0.12–0.26) mmHg/week, p &lt; 0.001], DBP [0.09 (0.05–0.14) mmHg/week, p &lt; 0.001], and hypertension [OR (95%CI): 1.03 (1.01–1.05), p = 0.010]. A baseline history of hypertension was associated with higher SBP by 13.45 (8.73–18.17) mmHg, higher DBP by 5.57 (2.02–9.12) mmHg, and 42.22 (6.60–270.08) times the odds of being hypertensive at each timepoint, compared to those without.ConclusionBlood pressure increased after inpatient rehabilitation over the first 12 months post-stroke, especially among those with a history of hypertension. The 4-week aerobic gait training intervention did not influence this trajectory

Lese-Rechtschreib-Störung. Die Bedeutung der phonologischen Informationsverarbeitung für den Schriftspracherwerb

Ptok M, Berendes K, Gottal S, Grabherr B, Schneeberg J, Wittler M. Lese-Rechtschreib-Störung. Die Bedeutung der phonologischen Informationsverarbeitung für den Schriftspracherwerb. HNO. 2007;55(9):737-748