Cytokine enrichment in deep cerebellar nuclei is contributed by multiple glial populations and linked to reduced amyloid plaque pathology.

Alzheimer's disease (AD) pathology and amyloid-beta (Aß) plaque deposition progress slowly in the cerebellum compared to other brain regions, while the entorhinal cortex (EC) is one of the most vulnerable regions. Using a knock-in AD mouse model (App KI), we show that within the cerebellum, the deep cerebellar nuclei (DCN) has particularly low accumulation of Aß plaques. To identify factors that might underlie differences in the progression of AD-associated neuropathology across regions, we profiled gene expression in single nuclei (snRNAseq) across all cell types in the DCN and EC of wild-type (WT) and App KI male mice at age 7 months. We found differences in expression of genes associated with inflammatory activation, PI3K-AKT signalling, and neuron support functions between both regions and genotypes. In WT mice, the expression of interferon-response genes in microglia is higher in the DCN than the EC and this enrichment is confirmed by RNA in situ hybridisation, and measurement of inflammatory cytokines by protein array. Our analyses also revealed that multiple glial populations are responsible for establishing this cytokine-enriched niche. Furthermore, homogenates derived from the DCN induced inflammatory gene expression in BV2 microglia. We also assessed the relationship between the DCN microenvironment and Aß pathology by depleting microglia using a CSF1R inhibitor PLX5622 and saw that, surprisingly, the expression of a subset of inflammatory cytokines was increased while plaque abundance in the DCN was further reduced. Overall, our study revealed the presence of a cytokine-enriched microenvironment unique to the DCN that when modulated, can alter plaque deposition.

CREB-regulated transcription during glycogen synthesis in astrocytes.

Glycogen storage, conversion and utilization in astrocytes play an important role in brain energy metabolism. The conversion of glycogen to lactate through glycolysis occurs through the coordinated activities of various enzymes and inhibition of this process can impair different brain processes including formation of long-lasting memories. To replenish depleted glycogen stores, astrocytes undergo glycogen synthesis, a cellular process that has been shown to require transcription and translation during specific stimulation paradigms. However, the detail nuclear signaling mechanisms and transcriptional regulation during glycogen synthesis in astrocytes remains to be explored. In this report, we study the molecular mechanisms of vasoactive intestinal peptide (VIP)-induced glycogen synthesis in astrocytes. VIP is a potent neuropeptide that triggers glycogenolysis followed by glycogen synthesis in astrocytes. We show evidence that VIP-induced glycogen synthesis requires CREB-mediated transcription that is calcium dependent and requires conventional Protein Kinase C but not Protein Kinase A. In parallel to CREB activation, we demonstrate that VIP also triggers nuclear accumulation of the CREB coactivator CRTC2 in astrocytic nuclei. Transcriptome profiles of VIP-induced astrocytes identified robust CREB transcription, including a subset of genes linked to glucose and glycogen metabolism. Finally, we demonstrate that VIP-induced glycogen synthesis shares similar as well as distinct molecular signatures with glucose-induced glycogen synthesis, including the requirement of CREB-mediated transcription. Overall, our data demonstrates the importance of CREB-mediated transcription in astrocytes during stimulus-driven glycogenesis.

A systematic review on the links between emotion regulation difficulties and obsessive-compulsive disorder.

BACKGROUND: Growing evidence suggests a link between emotion regulation (ER) deficits and obsessive-compulsive symptoms (OCS). AIMS: A systematic review was conducted to integrate empirical research on the nature of ER difficulties associated with obsessive-compulsive disorder (OCD), validated measures of ER for OCD and evidence base for psychological interventions targeting ER difficulties in OCD. METHODS: Database searches were conducted on CINAHL, Cochrane Library, EMBASE, MEDLINE, PUBMED, PsycINFO and Scopus with keywords related to ER and OCD. 2609 articles were found, six were identified from other sources and 21 studies were included in this review. The review was registered on PROSPERO (CDR42020184076). RESULTS: The non-acceptance of emotions was the most consistently related to OCS - albeit not uniformly with all OCS dimensions. There was also some evidence suggesting that difficulties in impulse-control, accessing effective ER strategies and engaging in goal-directed behaviours to be related to OCS. No OCD-specific ER measure was identified. Interventions with ER components appeared to be promising for the treatment of OCD. FUTURE DIRECTIONS: Recommendations on how to build on the existing literature and improve the quality of evidence were provided.

Profiling of objects with height steps by wavelet analysis of shadow moiré fringes.

A temporal wavelet analysis algorithm is proposed for shadow-moiré-based three-dimensional surface profiling on objects having discontinuous height steps. A grating is positioned close to an object, and its shadow is observed through the grating. The moiré fringe patterns vary when the grating is in-plane rotating. A series of fringe patterns are captured by a CCD camera at different rotating angles. Phase values are evaluated point by point with the continuous wavelet transform. From the phase values of each point on the object, the distance between the object and the grating can be retrieved. The surface profile is obtained without temporal or spatial phase unwrapping. This technique is applicable to objects with discontinuous height steps, which are impossible to measure with conventional shadow moiré topography. Two specimens are tested to demonstrate the validity of the method: One is an object with a height step of 1.6 mm, and another is a small coin with unevenness of less than 0.2 mm. The experimental results are compared with test results by use of the mechanical stylus method.