Neuroscience
-
Practice Guideline
Interferon-gamma facilitates neurogenesis by activating Wnt/β-catenin cell signaling pathway via promotion of STAT1 regulation of the β-catenin promoter.
Interferon-gamma (IFN-γ) is critical for central nervous system (CNS) functions and it may be a promising treatment to stimulate CNS regeneration. However, previous studies reported inconsistent results, and the molecular mechanisms remain controversial. Here we show that IFN-γ-treated mice via intraperitoneal injection have elevated IFN-γ level in central hippocampus and superior cognitive behaviors IFN-γ could activates the level of protein expression of Wnt7a, β-catenin, and CyclinD1 in Wnt/β-catenin signaling pathway of mice hippocampus. ⋯ It is also discovered firstly that Wnt/β-catenin and JAK/STAT pathways form cross-links through STAT1. Promoting neurogenesis through immune stimulation might be a promising strategy for repairing the diseased/injured CNS. This study provides a scientific basis for immunomodulation to promote nerve regeneration and offer a new therapeutic direction for central nervous system regeneration.
-
PRRT2 loss-of-function mutations have been associated with familial paroxysmal kinesigenic dyskinesia (PKD), infantile convulsions and choreoathetosis, and benign familial infantile seizures. Dystonia is the foremost involuntary movement disorder manifest by patients with PKD. Using a lacZ reporter and quantitative reverse-transcriptase PCR, we mapped the temporal and spatial distribution of Prrt2 in mouse brain and showed the highest levels of expression in cerebellar cortex. ⋯ In addition to impaired performance on several motor tasks, approximately 5% of Prrt2-/- mice exhibited overt PKD with clear face validity manifest as dystonia. In Prrt2 mutants, we found reduced parallel fiber facilitation at parallel fiber-Purkinje cell synapses, reduced Purkinje cell excitability, and normal cerebellar nuclear excitability, establishing a potential mechanism by which altered cerebellar activity promotes disinhibition of the cerebellar nuclei, driving motor abnormalities in PKD. Overall, our findings replicate, refine, and expand upon previous work with PRRT2 mouse models, contribute to understanding of paroxysmal disorders of the nervous system, and provide mechanistic insight into the role of cerebellar cortical dysfunction in dystonia.
-
The morphology of dendritic arbors determines the location, strength and interaction of synaptic inputs. It is therefore important to understand the factors regulating dendritic arborization both during development and in situations of physiological or pathological plasticity. We have recently shown that VEGF-D (Vascular Endothelial Growth Factor D) is required to maintain length and complexity of basal dendrites in mouse hippocampal pyramidal cells. ⋯ We report opposing, layer-specific effects of VEGF-D knockdown which resulted in shrinkage of basal and increased complexity of apical dendrites. Synaptic potentials and layer-specific voltage gradients during network oscillations remained, however, unaltered. These findings reveal a high spatial selectivity of VEGF-D effects at the sub-cellular level, and strong homeostatic mechanisms which keep spatially segregated synaptic inputs in a balance.
-
Peripheral nerve injury induces functional reorganization of the central nervous system. The mechanisms underlying this reorganization have been widely studied. Our previous study involving multiple-site optical recording reported that a neural excitatory wave induced by somatic stimulation begins in a small area and propagates in the cortex. ⋯ Second, changes in the propagation wave pattern were analyzed. Ulnar nerve injury decreased the propagation velocity in the medial direction but the median nerve injury induced no changes. These results indicated that the propagation wave pattern is readily altered, even immediately after nerve injury, and suggest that this immediate change in the spatio-temporal pattern is one of the factors contributing to the cortical reorganization.