Differential Interferon Signaling Regulation and Oxidative Stress Responses in the Cerebral Cortex and Cerebellum Could Account for the Spatiotemporal Pattern of Neurodegeneration in Niemann-Pick Disease Type C.

Niemann-Pick disease type C (NPC) is a fatal neurodegenerative condition caused by genetic mutations of the NPC1 or NPC2 genes that encode the NPC1 and NPC2 proteins, respectively, which are believed to be responsible for cholesterol efflux from late-endosomes/lysosomes. The pathogenic mechanisms that lead to neurodegeneration in NPC are not well understood. There are, however, well-defined spatiotemporal patterns of neurodegeneration that may provide insight into the pathogenic process. For example, the cerebellum is severely affected from early disease stages, compared with cerebral regions, which remain relatively spared until later stages. Using a genome-wide transcriptome analysis, we have recently identified an aberrant pattern of interferon activation in the cerebella of pre-symptomatic Npc1-/- mice. Here, we carried out a comparative transcriptomic analysis of cerebral cortices and cerebella of pre-symptomatic Npc1-/- mice and age-matched controls to identify differences that may help explain the pathological progression within the NPC brain. We report lower cerebral expression of genes within interferon signaling pathways, and significant differences in the regulation of oxidative stress, compared with the cerebellum. Our findings suggest that a delayed onset of interferon signaling, possibly linked to lower oxidative stress, may account for the slower onset of cerebral cortical pathology in the disease.

3D doppler ultrasound imaging of cerebral blood flow for assessment of neonatal hypoxic-ischemic brain injury in mice.

Cerebral blood flow (CBF) acutely reduces in neonatal hypoxic-ischemic encephalopathy (HIE). Clinic studies have reported that severe CBF impairment can predict HIE outcomes in neonates. Herein, the present study uses a non-invasive 3D ultrasound imaging approach to evaluate the changes of CBF after HI insult, and explores the correlation between CBF alterations and HI-induced brain infarct in mouse pups. The neonatal HI brain injury was induced in postnatal day 7 mouse pups using the Rice-Vannucci model. Non-invasive 3D ultrasound imaging was conducted to image CBF changes with multiple frequencies on mouse pups before common carotid artery (CCA) ligation, immediately after ligation, and 0 or 24 hours after HI. Vascularity ratio of the ipsilateral hemisphere was acutely reduced after unilateral ligation of the CCA alone or in combination with hypoxia, and partially restored at 24 hours after HI. Moreover, regression analysis showed that the vascularity ratio of ipsilateral hemisphere was moderately correlated with brain infarct size 24 hours after HI, indicating that CBF reduction contributes to of HI brain injury. To further verify the association between CBF and HI-induced brain injury, a neuropeptide C-type natriuretic peptide (CNP) or PBS was intranasally administrated to the brain of mouse pups one hour after HI insult. Brain infarction, CBF imaging and long-term neurobehavioral tests were conducted. The result showed that intranasal administration of CNP preserved ipsilateral CBF, reduced the infarct size, and improved neurological function after HI brain injury. Our findings suggest that CBF alteration is an indicator for neonatal HI brain injury, and 3D ultrasound imaging is a useful non-invasive approach for assessment of HI brain injury in mouse model.

The Plecoptera of Panama. IV. Description of the last nymphal instar for two species of Anacroneuria Klapálek (Plecoptera: Perlidae) from the Caldera River, Chiriquí, Panamá.

The last nymphal instars of Anacroneuria planicollis Klapálek, 1923 and A. quetzali Gutiérrez-Fonseca and Springer, 2015 are described from the Caldera River, Chiriquí Province, Panamá. The adult female of A. quetzali is associated for the first time and described also from the Caldera River, Chiriquí Province, Panamá.

Anacroneuria (Plecoptera: Perlidae) del río Caldera, Chiriquí, Panamá: nuevos registros de distribución, y comentarios sobre distribución altitudinal y variación estacional / Anacroneuria (Plecoptera: Perlidae) from Caldera River, Chiriquí, Panamá: new distribution records, and comments on altitudinal distribution and seasonal variation

Resumen Plecoptera es un grupo basal de insectos acuáticos, también conocidos como "moscas de piedra". Con el objetivo de contribuir al conocimiento taxonómico y ecológico del género Anacroneuria, se realizaron recolectas de ninfas en la parte alta y media del río Caldera, en la provincia de Chiriquí. Para esto se hicieron giras de campo una vez al mes de enero a diciembre de 2015. En siete estaciones de muestreo, se recolectaron ninfas en rocas y hojarasca sumergida, de forma manual con pinzas entomológicas y con red triangular, para su posterior cría en sistemas de acuarios en el laboratorio. Se recolectaron 485 ninfas, con la emergencia de 138 adultos. Cinco especies de Anacroneuria: Anacroneuria annulipalpis, A. benedettoi, A. planicollis, A. quetzali, A. marca y dos especies no identificadas fueron determinadas a través de la crianza de ninfas en laboratorio. El rango de distribución de A. benedettoi fue extendido a la provincia de Chiriquí. El primer registro de A. quetzalipara Panamá es comentado. Se aporta datos de distribución altitudinal, variabilidad estacional y requerimientos ambientales. Se recomienda ampliar los estudios sobre las asociaciones de ninfas con las formas adultas en otras áreas de Panamá y del Neotrópico, así como incrementar el conocimiento sobre la biología y ecología de este grupo.

Abstract Plecoptera order is a basal group of aquatic insects, also known as stonefly. In order to contribute to the taxonomic and ecological knowledge of the genus Anacroneuria, nymphs were collected in the upper and low parts of the Caldera River, in the Chiriquí province. For this, field trips were carried out once a month, from January to December of 2015. A total of seven stations were sampled, and nymphs were collected on rocks and submerged leaf litter, manually with entomological tweezers, and with a triangular net; nymphs were later transported and reared in aquarium systems in the laboratory, and their growth was followed. A total of 485 nymphs were collected, with the emergence of 138 adults. Five species of Anacroneuria: Anacroneuriaannulipalpis, A. benedettoi, A. planicollis, A. quetzali, A. marca and two unknown species were obtained after nymphs rearing. The distribution range of A. benedettoi was extended to the Chiriqui province. The first record for A. quetzaliin Panamá is commented. In addition, data of altitudinal distribution, seasonal variability and environment requirements were mentioned. We recommend to expand studies on Plecoptera nymph associations with adult forms in other areas of Panama and the Neotropics, as well as to increase the knowledge about their biology and ecology. Rev. Biol. Trop. 66(1): 164-177. Epub 2018 March 01.