Enteric glia mediate neuronal outgrowth through release of neurotrophic factors

Previous studies have shown that transplanted enteric glia enhance axonal regeneration, reduce tissue damage, and promote functional recovery following spinal cord injury. However, the mechanisms by which enteric glia mediate these beneficial effects are unknown. Neurotrophic factors can promote neuronal differentiation, survival and neurite extension. We hypothesized that enteric glia may exert their protective effects against spinal cord injury partially through the secretion of neurotrophic factors. In the present study, we demonstrated that primary enteric glia cells release nerve growth factor, brain-derived neurotrophic factor and glial cell line-derived neurotrophic factor over time with their concentrations reaching approximately 250, 100 and 50 pg/mL of culture medium respectively after 48 hours. The biological relevance of this secretion was assessed by incubating dissociated dorsal root ganglion neuronal cultures in enteric glia-conditioned medium with and/or without neutralizing antibodies to each of these proteins and evaluating the differences in neurite growth. We discovered that conditioned medium enhances neurite outgrowth in dorsal root ganglion neurons. Even though there was no detectable amount of neurotrophin-3 secretion using ELISA analysis, the neurite outgrowth effect can be attenuated by the antibody-mediated neutralization of each of the aforementioned neurotrophic factors. Therefore, enteric glia secrete nerve growth factor, brain-derived neurotrophic factor, glial cell line-derived neurotrophic factor and neurotrophin-3 into their surrounding environment in concentrations that can cause a biological effect.     

White matter microstructure in habit and reward circuits in anorexia nervosa: Insights from a neurite orientation dispersion and density imaging study

Background

Behavioral features of anorexia nervosa (AN) suggest abnormalities in reward and habit. Neuroimaging evidence suggests morphometric and functional perturbations within these circuits, although fewer studies have assessed white matter characteristics in AN, and no studies to date have assessed white matter microstructure in AN.

Methods

In this brain imaging study, 29 female adolescents with partially or fully weight-restored AN and 27 healthy controls, all between 10 and 19 years, underwent whole-brain multi-shell diffusion tensor imaging. Utilizing neurite orientation dispersion and density imaging methods, we investigated group differences in white matter neurite density, orientation dispersion, and myelin density in tracts between prominent nodes of the reward circuit (ventral tegmental area (VTA) to nucleus accumbens (NAcc)) and the habit circuit (sensory motor area [SMA] to putamen).

Results

Findings revealed reduced neurite (F = 5.20, p = 0.027) and myelin density (F = 5.39, p = 0.025) in the left VTA-NAcc tract, and reduced orientation dispersion in the left (F = 7.00, p = 0.011) and right (F = 6.77, p = 0.012) VTA-NAcc tract. There were no significant group differences in the SMA-putamen tract. Significant relationships, after corrections, were not evident between tract microstructure and reward responsiveness, compulsive behaviors, illness duration, or BMI.

Conclusions

Adolescents with AN exhibit less dense, undermyelinated, and less dispersed white matter tracts connecting prominent reward system nodes, which could potentially signify underutilization of this part of the reward circuit. These results provide a detailed examination of white matter microstructure in tracts underlying instrumental behavioral phenotypes contributing to illness in AN.     

Corticospinal fibers with different origins impair in amyotrophic lateral sclerosis: A neurite orientation dispersion and density imaging study

Aims

To investigate microstructural impairments of corticospinal tracts (CSTs) with different origins in amyotrophic lateral sclerosis (ALS) using neurite orientation dispersion and density imaging (NODDI).

Methods

Diffusion-weighted imaging data acquired from 39 patients with ALS and 50 controls were used to estimate NODDI and diffusion tensor imaging (DTI) models. Fine maps of CST subfibers originating from the primary motor area (M1), premotor cortex, primary sensory area, and supplementary motor area (SMA) were segmented. NODDI metrics (neurite density index [NDI] and orientation dispersion index [ODI]) and DTI metrics (fractional anisotropy [FA] and mean/axial/radial diffusivity [MD/AD/RD]) were computed.

Results

The patients with ALS showed microstructural impairments (reflected by NDI, ODI, and FA reductions and MD, AD, and RD increases) in CST subfibers, especially in M1 fibers, which correlated with disease severity. Compared with other diffusion metrics, NDI yielded a higher effect size and detected the greatest extent of CST subfibers damage. Logistic regression analyses based on NDI in M1 subfiber yielded the best diagnostic performance compared with other subfibers and the whole CST.

Conclusions

Microstructural impairment of CST subfibers (especially those originating from M1) is the key feature of ALS. The combination of NODDI and CST subfibers analysis may improve diagnosing performance for ALS.     

The neurotrophic activities of brain-derived neurotrophic factor are potentiated by binding with apigenin,a common flavone in vegetables,in stimulating the receptor signaling

Aims

We aimed to identify the neurotrophic activities of apigenin (4′,5,7-trihydroxyflavone) via its coordination with brain-derived neurotrophic factor (BNDF) and an elevated signaling of tyrosine kinase receptor B (Trk B receptor).

Methods

The direct binding of apigenin to BDNF was validated by ultrafiltration and biacore assay. Neurogenesis, triggered by apigenin and/or BDNF, was determined in cultured SH-SY5Y cells and rat cortical neurons. The amyloid-beta (Aβ)_25-35-induced cellular stress was revealed by propidium iodide staining, mitochondrial membrane potential, bioenergetic analysis, and formation of reactive oxygen species levels. Activation of Trk B signaling was tested by western blotting.

Results

Apigenin and BDNF synergistically maintained the cell viability and promoted neurite outgrowth of cultured neurons. In addition, the BDNF-induced neurogenesis of cultured neurons was markedly potentiated by applied apigenin, including the induced expressions of neurofilaments, PSD-95 and synaptotagmin. Moreover, the synergy of apigenin and BDNF alleviated the (Aβ)_25-35-induced cytotoxicity and mitochondrial dysfunction. The synergy could be accounted by phosphorylation of Trk B receptor, and which was fully blocked by a Trk inhibitor K252a.

Conclusion

Apigenin potentiates the neurotrophic activities of BDNF through direct binding, which may serve as a possible treatment for its curative efficiency in neurodegenerative diseases and depression.     

Zebrafish Erc1b mediates motor innervation and organization of craniofacial muscles in control of jaw movement

Background: Movement of the lower jaw, a common behavior observed among vertebrates, is required for eating and processing food. This movement is controlled by signals sent from the trigeminal motor nerve through neuromuscular junctions (NMJs) to the masticatory muscles. Dysfunctional jaw movements contribute to craniomandibular disorders, yet the pathophysiology of these disorders is not well understood, as limited studies have been conducted on the molecular mechanisms of jaw movement. Results: Using erc1b/kim^m533 genetic loss of function mutant, we evaluated lower jaw muscle organization and innervation by the cranial motor nerves in developing zebrafish. Using time-lapse confocal imaging of the erc1b mutant in a transgenic fluorescent reporter line, we found delayed trigeminal nerve growth and disrupted nerve branching architecture during muscle innervation. By automated 3D image analysis of NMJ distribution, we identified an increased number of small, disorganized NMJ clusters in erc1b mutant larvae compared to WT siblings. Using genetic replacement experiments, we determined the Rab GTPase binding domain of Erc1b is required for cranial motor nerve branching, but not NMJ organization or muscle attachment. Conclusions: We identified Erc1b/ERC1 as a novel component of a genetic pathway contributing to muscle organization, trigeminal nerve outgrowth, and NMJ spatial distribution during development that is required for jaw movement.