BDNF Boosts Spike Fidelity in Chaotic Neural Oscillations

Oscillatory activity and its nonlinear dynamics are of fundamental importance for information processing in the central nervous system. Here we show that in aperiodic oscillations, brain-derived neurotrophic factor (BDNF), a member of the neurotrophin family, enhances the accuracy of action potentials in terms of spike reliability and temporal precision. Cultured hippocampal neurons displayed irregular oscillations of membrane potential in response to sinusoidal 20-Hz somatic current injection, yielding wobbly orbits in the phase space, i.e., a strange attractor. Brief application of BDNF suppressed this unpredictable dynamics and stabilized membrane potential fluctuations, leading to rhythmical firing. Even in complex oscillations induced by external stimuli of 40 Hz (γ) on a 5-Hz (θ) carrier, BDNF-treated neurons generated more precisely timed spikes, i.e., phase-locked firing, coupled with θ-phase precession. These phenomena were sensitive to K252a, an inhibitor of tyrosine receptor kinases and appeared attributable to BDNF-evoked Na(+) current. The data are the first indication of pharmacological control of endogenous chaos. BDNF diminishes the ambiguity of spike time jitter and thereby might assure neural encoding, such as spike timing-dependent synaptic plasticity

Fifteen‐year survival and conditional survival of women with breast cancer in Osaka, Japan: A population‐based study

Abstract Background In recent years, the survival of patients with breast cancer has improved. However, few published studies have a longer than 10‐year follow‐up. Conditional relative survival (CRS), which is relative survival (RS) of patients who have survived beyond a certain period after diagnosis, is useful for assessing excess mortality among long‐term survivors compared with the general population. Methods This was a retrospective observational cohort study. Population‐based cancer registry data in Osaka, Japan were used to determine 15‐year RS and 5‐year CRS of women with breast cancer diagnosed between 2001 and 2002 and followed up for at least 15 years. Fifteen‐year RS and age‐standardized RS (ASR) were calculated by Ederer II and cohort methods. Five‐year CRS according to age group and extent of disease (localized, regional, and distant) was estimated for every year from diagnosis to 10 years. Results In the cohort of 4006 patients, the ASR declined progressively, the 5‐year ASR being 85.8%, 10‐year ASR 77.3%, and 15‐year ASR 71.6%. The overall 5‐year CRS exceeded 90% at 5 years after diagnosis, reflecting a small excess mortality compared with the general population. The 5‐year CRS of patients with regional and distant disease did not reach 90% within 10 years of follow‐up (89.4% for regional and 72.9% for distant disease 10 years after diagnosis), indicating that these patients had substantial excess mortality. Conclusion Long‐term survival data can help cancer survivors plan their lives and receive better medical care and support

The Wnt/Planar Cell Polarity Pathway Component Vangl2 Induces Synapse Formation through Direct Control of N-Cadherin

Although regulators of the Wnt/planar cell polarity (PCP) pathway are widely expressed in vertebrate nervous systems, their roles at synapses are unknown. Here, we show that Vangl2 is a postsynaptic factor crucial for synaptogenesis and that it coprecipitates with N-cadherin and PSD-95 from synapse-rich brain extracts. Vangl2 directly binds N-cadherin and enhances its internalization in a Rab5-dependent manner. This physical and functional interaction is suppressed by β-catenin, which binds the same intracellular region of N-cadherin as Vangl2. In hippocampal neurons expressing reduced Vangl2 levels, dendritic spine formation as well as synaptic marker clustering is significantly impaired. Furthermore, Prickle2, another postsynaptic PCP component, inhibits the N-cadherin-Vangl2 interaction and is required for normal spine formation. These results demonstrate direct control of classic cadherin by PCP factors; this control may play a central role in the precise formation and maturation of cell-cell adhesions at the synapse

Production of marmoset eggs and embryos from xenotransplanted ovary tissues

Abstract The common marmoset (Callithrix jacchus) has attracted attention as a valuable primate model for the analysis of human diseases. Despite the potential for primate genetic modification, however, its widespread lab usage has been limited due to the requirement for a large number of eggs. To make up for traditional oocyte retrieval methods such as hormone administration and surgical techniques, we carried out an alternative approach by utilizing ovarian tissue from deceased marmosets that had been disposed of. This ovarian tissue contains oocytes and can be used as a valuable source of follicles and oocytes. In this approach, the ovarian tissue sections were transplanted under the renal capsules of immunodeficient mice first. Subsequent steps consist of development of follicles by hormone administrations, induction of oocyte maturation and fertilization, and culture of the embryo. This method was first established with rat ovaries, then applied to marmoset ovaries, ultimately resulting in the successful acquisition of the late-stage marmoset embryos. This approach has the potential to contribute to advancements in genetic modification research and disease modeling through the use of primate models, promoting biotechnology with non-human primates and the 3Rs principle in animal experimentation