Neonatal stress disrupts the glymphatic system development and increases the susceptibility to Parkinson's disease in later life.

INTRODUCTION: Neonatal stress disrupts brain development and increases the risk of neurological disorders later in life. However, the impact of neonatal stress on the development of the glymphatic system and susceptibility to Parkinson's disease (PD) remains largely unknown. METHODS: Neonatal maternal deprivation (NMD) was performed on mice for 14 consecutive days to model chronic neonatal stress. Adeno-associated virus expressing A53T-α-synuclein (α-syn) was injected into the substantia nigra to establish PD model mice. Glymphatic activity was determined using in vivo magnetic resonance imaging, ex vivo fluorescence imaging and microplate assay. The transcription and expression of aquaporin-4 (AQP4) and other molecules were evaluated by qPCR, western blotting, and immunofluorescence. Animal's responses to NMD and α-syn overexpression were observed using behavioral tests. RESULTS: Glymphatic activity was impaired in adult NMD mice. AQP4 polarization and platelet-derived growth factor B (PDGF-B) signaling were reduced in the frontal cortex and hippocampus of both young and adult NMD mice. Furthermore, exogenous α-syn accumulation was increased and PD-like symptoms were aggravated in adult NMD mice. CONCLUSION: The results demonstrated that NMD could disrupt the development of the glymphatic system through PDGF-B signaling and increase the risk of PD later in life, indicating that alleviating neonatal stress could be beneficial in protecting the glymphatic system and reducing susceptibility to neurodegeneration.

Development of a paper-based microfluidic analytical device by a more facile hydrophobic substrate generation strategy.

Microfluidic paper-based analytical devices (µPADs) have a significant potential in developing portable and disposable point-of-care testing (POCT). Herein, a facile, rapid, cost-effective and environment friendly strategy for µPADs fabrication is proposed. Specifically, the substrate paper was hydrophobized by coating with trimethoxysilane (TOS), and then the selected area was hydrophilized by treating with surfactant. The whole fabrication process was implemented within 7 min, with no need for complex pre-treatment, high-temperature and special equipment. As a proof-of-concept application, the as-prepared µPAD was applied to determination of the glucose content in human serum samples. The results agreed well with those obtained by a glucometer. We believe that the µPADs fabrication method proposed here could provide a facile, rapid and low-cost reference for other related studies.