Browsing by Subject "spine"

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  • Gonda, Yuko; Namba, Takashi; Hanashima, Carina (2020)
    The formation of the neocortex relies on intracellular and extracellular signaling molecules that are involved in the sequential steps of corticogenesis, ranging from the proliferation and differentiation of neural progenitor cells to the migration and dendrite formation of neocortical neurons. Abnormalities in these steps lead to disruption of the cortical structure and circuit, and underly various neurodevelopmental diseases, including dyslexia and autism spectrum disorder (ASD). In this review, we focus on the axon guidance signaling Slit-Robo, and address the multifaceted roles of Slit-Robo signaling in neocortical development. Recent studies have clarified the roles of Slit-Robo signaling not only in axon guidance but also in progenitor cell proliferation and migration, and the maturation of neocortical neurons. We further discuss the etiology of neurodevelopmental diseases, which are caused by defects in Slit-Robo signaling during neocortical formation.
  • Moliner, Rafael (Helsingin yliopisto, 2019)
    Classical and rapid-acting antidepressant drugs have been shown to reinstate juvenile-like plasticity in the adult brain, allowing mature neuronal networks to rewire in an environmentally-driven/activity-dependent process. Indeed, antidepressant drugs gradually increase expression of brain-derived neurotrophic factor (BDNF) and can rapidly activate signaling of its high-affinity receptor TRKB. However, the exact mechanism of action underlying drug-induced restoration of juvenile-like plasticity remains poorly understood. In this study we first characterized acute effects of classical and rapid-acting antidepressant drugs on the interaction between TRKB and postsynaptic density (PSD) proteins PSD-93 and PSD-95 in vitro. PSD proteins constitute the core of synaptic complexes by anchoring receptors, ion channels, adhesion proteins and various signaling molecules, and are also involved in protein transport and cell surface localization. PSD proteins have in common their role as key regulators of synaptic structure and function, although PSD-93 and PSD-95 are associated with different functions during development and have opposing effects on the state of plasticity in individual synapses and neurons. Secondly, we investigated changes in mobility of TRKB in dendritic structures in response to treatment with antidepressant drugs in vitro. We found that antidepressant drugs decrease anchoring of TRKB with PSD-93 and PSD-95, and can rapidly increase TRKB turnover in dendritic spines. Our results contribute to the mechanistic model explaining drug-induced restoration of juvenile-like neuronal plasticity, and may provide a common basis for the effects of antidepressant drugs.
  • Repo, Jussi P.; Häkkinen, Arja H.; Porkka, Tuukka; Häkkinen, Keijo; Kautiainen, Hannu; Kyrölä, Kati; Neva, Marko H. (2019)
    Purpose: Interleukin 6 (IL-6) and the acute phase C-reactive protein (CRP) blood concentrations after lumbar spine fusion may be affected by age. The purpose of this prospective observational study was to assess postoperative serum levels of pro-inflammatory IL-6 and CRP after instrumented lumbar spine fusion surgery. We hypothesized that older patients would have increased levels of IL-6 and CRP after surgery. Methods: IL-6 and high-sensitive CRP biochemical marker levels were measured before instrumented spinal fusion, and postoperatively at 1 and 3 days, 6 weeks, and 3 months. The 49 patients in this sample were divided into two groups: age 60 years (n = 26). Results: Acute changes in IL-6 high-sensitivity and CRP from preoperative levels to postoperative day (POD) 1 increased with age. Mean (95% CI) difference between the age-groups in changes of IL-6 at PODs 1 and 3 was 45 pg/ml (10-83, p = 0.014) and 20 pg/ml (5-36, p = 0.021), respectively. Mean (95% CI) difference between groups in changes of CRP at PODs 1 and 3 was 9.6 mg/l (-3.5 to 22.7, p = 0.47) and 24.8 mg/l (-17 to 67, p = 0.33), respectively. Both groups had decreased IL-6 and CRP levels at 6 weeks after surgery compared to the preoperative level. Conclusions: Elevation of IL-6 and CRP is stronger in patients over 60 years old after instrumented lumbar spinal fusion. The CRP and IL-6 are sensitive markers for acute postoperative inflammation. Even high acute CRP values do not necessarily indicate postoperative infection.