microglia-as-surrogate-biosensor-to-determine-nanoparticle

Microglia as a Surrogate Biosensor to Determine Nanoparticle Neurotoxicity

Nanoparticles found in air pollutants can alter neurotransmitter profiles, increase neuroinflammation, and alter brain function. Therefore, the assay ...

Minneapolis Veterans Affairs Health Care System

University of Minnesota

Visits to the emergency department (ED) are stressful for any patient and pose special challenges and potential barriers to care for those with autism spectrum disorder (ASD). In addition, people (both children and adults) with ASD differ in their perception of, or responses to, environmental stimuli. Some people with ASD present with sensory defensiveness that is environmentally moderated, but there is a gap in our knowledge about patterns or thresholds of stimulation that kindle behavioral responses. We systematically recorded visual and auditory stimuli in an ED. Data were collected in four areas, hallway, doorway of waiting room, chair in waiting room, and treatment room, over several weeks and times of day. The mean light intensity ranged from 127 to 184 lux. There were significant differences (F = 16.77, df = 3, p > 0.001) between the five ED locations. Mean sound levels ranged from a high of 63.291 dB in the waiting room chair to a low of 51.289 dB in the treatment room. The highest consistent level of noise was recorded while sitting in the waiting room chair (60.657-63.291 dB). The findings suggest significant differences in light and sound intensity in common ED locations, with the highest mean readings of light and noise in the waiting areas. The differences and descriptions of light and sound patterns support the need for additional studies in both the measurement of the ED environment and its role in stimulating sensory defensiveness in people with ASD.

Sensory stimuli as obstacles to emergency care for children with autism spectrum disorder.

Excess dietary saturated fatty acids such as palmitic acid (PA) induce peripheral and hypothalamic inflammation. Hypothalamic inflammation, mediated in part by microglial activation, contributes to metabolic dysregulation. In rodents, high fat diet-induced microglial activation results in nuclear translocation of nuclear factor-kappa B (NFκB), and increased central pro-inflammatory cytokines tumor necrosis factor alpha (TNF-α) and interleukin-6 (IL-6). The hypothalamic neuropeptide orexin A (OXA, hypocretin 1) is neuroprotective in brain. In cortex, OXA can also reduce inflammation and neurodegeneration through a microglial-mediated pathway. Whether hypothalamic orexin neuroprotection mechanisms depend upon microglia is unknown. To address this issue, we evaluated effects of OXA and PA on inflammatory response in immortalized murine microglial and hypothalamic neuronal cell lines. We demonstrate for the first time in microglial cells that exposure to PA increases gene expression of orexin-1 receptor but not orexin-2 receptor. Pro-inflammatory markers IL-6, TNF-α, and inducible nitric oxide synthase in microglial cells are increased following PA exposure, but are reduced by pretreatment with OXA. The anti-inflammatory marker arginase-1 is increased by OXA. Finally, we show hypothalamic neurons exposed to conditioned media from PA-challenged microglia have increased cell survival only when microglia were pretreated with OXA. These data support the concept that OXA may act as an immunomodulatory regulator of microglia, reducing pro-inflammatory cytokines and increasing anti-inflammatory factors to promote a favorable neuronal microenvironment.

Role of orexin A signaling in dietary palmitic acid-activated microglial cells.

Large time/memory costs have constituted a significant obstacle for accurately analyzing surface acoustic waves (SAWs) in large size two-dimensional (2-D) piezoelectric phononic crystals (PnCs). To overcome this obstacle, this study introduces the unit P matrix and its associated cascading. To obtain an accurate unit P matrix, the Y parameters of the SAW delay lines were derived using a three-dimensional (3-D) finite element model (FEM) with and without 2-D piezoelectric PnCs, respectively, on the transmitting path. A time window function was adopted to extract the desired signals from the P matrix analysis. Then, unit P matrix cascading was used to obtain SAW propagation parameters for the large size piezoelectric PnCs. Using this method, the SAW in aluminum (Al) /128º-YXLiNbO3 PnCs was analyzed over 150 periods. Experiments were also conducted. To choose the appropriate size of the unit P matrix, the variance between experimental results and theoretical results, and time/memory cost were compared for different periods. The results indicate that cascading by unit P matrix of 25 PnCs periods can be appropriately adopted to accurately derive the SAW propagation parameters over 150 periods. This indicates the accuracy of the unit P matrix derived by 3-D FEM and the effectiveness of P matrix analysis.

Ce Yuan

Minneapolis Veterans Affairs Health Care System

Microglia as a Surrogate Biosensor to Determine Nanoparticle Neurotoxicity