Chronic VEGFR-3 signaling preserves dendritic arborization and sensitization under stress

Resource type
Authors/contributors
Title
Chronic VEGFR-3 signaling preserves dendritic arborization and sensitization under stress
Abstract
Dendritic arborization is critical for the establishment and maintenance of precise neural circuits. Vascular endothelial growth factor D (VEGF-D), well-characterized as a “lymphangiogenic” growth factor, reportedly maintains dendritic arborization and synaptic strength in the hippocampus of adult mice through VEGF receptor (VEGFR-3) signaling. Here, we investigated the effect of chronic VEGFR-3-specific activation on adipose arbor morphometry using the Adipo-VD mouse, a model of inducible, adipose-specific VEGF-D overexpression. We examined whether adipose tissue innervation was preserved or functionally different in Adipo-VD mice during stress in vivo and if VEGFR-3 signaling afforded neuroprotection to challenged neurons in vitro. Chronic VEGFR-3 signaling in Adipo-VD subcutaneous adipose tissue resulted in a reduction in the dendrite length, dendritic terminal branches (filament length), dendritic terminal branch volume (filament volume), but increased dendrite branching. We also identified reduced stimulus-evoked excitatory sympathetic nerve activity in Adipo-VD mice. Following 6-hydroxydopamine (6-OHDA) denervation, Adipo-VD dendritic arbors were preserved, including improved dendritic branch volume, length, and dendritic branches than in wildtype tissues. In vitro, we found that chronic elevation of VEGFR-3 signaling in developing mVC neurons changes the dendritic arbor complexity and improves stress-induced structure remodeling. Developing neurons are conferred neuroprotection against stress, potentially by upregulation of proteolytic conversion of pro-BDNF to mature BDNF. Mature neurons, however, display improved dendritic arbor complexity, and unaltered dendritic structural remodeling and improved resistance to stress with VEGFR-3 signaling. Overall, chronically increasing VEGFR-3 signaling in neurons has a synergistic impact on neurosensitization and neuroprotection during stress.
Publication
Brain, Behavior, and Immunity
Date
August 11, 2021
Journal Abbr
Brain, Behavior, and Immunity
Language
en
ISSN
0889-1591
Accessed
8/23/21, 1:32 PM
Library Catalog
ScienceDirect
Lipedema Foundation Award
LF10
Citation
Chakraborty, A., Upadhya, R., Usman, T. A., Shetty, A. K., & Rutkowski, J. M. (2021). Chronic VEGFR-3 signaling preserves dendritic arborization and sensitization under stress. Brain, Behavior, and Immunity. https://doi.org/10.1016/j.bbi.2021.08.007
Topic