Proteins secreted by brain arteriolar smooth muscle cells are instructive for neural development

Li, Xuzhao; Zhou, Lili; Zhang, Xiaoxuan; Jin, Yuxiao; Zhao, Bingrui; Zhang, Dongdong; Xi, Chengjie; Ruan, Jiayu; Zhu, Zhu; Jia, Jie–Min

doi:10.1186/s13041-022-00983-y

Cited by 3 publications

(4 citation statements)

References 40 publications

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“…Sorted cells were cultured in SMCM for further assay. The purity of cells sorted by the same method had been verified in the published paper (22).…”

mentioning

confidence: 85%

“…The electro-motor-driven brush stimulated the whisker longitudinally for 1 minute at a frequency of 12Hz. The principle of laser speckle contrast imaging has been described in the previous paper (21), and the operation referred to in the published paper ( 34, 58, 59 ). Laser Speckle Image System (RWD, RFSLI ZW/RFSLI III, CHN) was used to monitor the CBF change in the ROI of the opposite barrel cortex of mice.…”

Section: Methodsmentioning

confidence: 99%

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Local neurovascular coupling in the amygdala is responsible for context-dependent emotional adjustment

Ruan

Xie

Quan

et al. 2023

Preprint

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Proper brain function depends on intact neurovascular coupling (NVC). Through NVC, local cerebral blood flow (CBF) is rapidly increased in activated cerebral regions to meet the corresponding demands of neural activities. NVC has been believed to support advanced cerebral functions such as complex emotional homeostasis. However, few studies provide causal link evidence with specific molecular and cellular identities. Here, using RNAscope, cell-type specific conditional knockout (cKO) perturbation in BL6/C57 mice, laser speckle contrast imaging, and mouse behavior assays, we demonstrated that the N-methyl-D-aspartic acid (NMDA) receptor noncore subunit NR2D is only expressed in cerebral arteriole smooth muscle cells (aSMCs) but not in peripheral aSMCs. Both aSMC-NR2D cKO and aSMC-NR2D+NMDA receptor subunit 1 (NR1) double cKO mice displayed a severe decline in functional hyperemia induced by whisker stimulation. In addition, the NR2D pathway was independent of previously demonstrated COX-2-PGE2-dependent mechanism and high-fat diet (HFD)-induced impairments in NVC. Caldesmon is a potential downstream protein in the NR2D pathway for NVC regulation. Notably, we demonstrated that NVC deficits caused abnormalities in complex emotional behaviors, such as anxiety-like behaviors (exhibiting increased defecation and urine), reduced curiosity and decreased fear instinct (displaying less fear of aggressive CD1 mice). Furthermore, fear-response gene c-FOS expression in the amygdala neurons was attenuated in aSMC-NR2D knockout mice after response to acute stresses. In contrast, its expression level remained unchanged in the non-fear-related cerebral regions such as the piriform cortex and hippocampus. These findings demonstrated that inadequate functional hyperemia impaired cerebral complex emotional functions and suggested a co-existence of anxiety and fearlessness in single individuals.

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“…Sorted cells were cultured in SMCM for further assay. The purity of cells sorted by the same method had been verified in the published paper (22).…”

mentioning

confidence: 85%

Section: Methodsmentioning

confidence: 99%

Local neurovascular coupling in the amygdala is responsible for context-dependent emotional adjustment

Ruan

Xie

Quan

et al. 2023

Preprint

Self Cite

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“…It is well documented that development of the nervous system is highly dependent on appropriate signaling from adjacent non-neural tissues. Vascular smooth muscle cells in the brain, for example, secrete factors such as thrombospondin, a known synaptogenic factor, to promote neurite formation in mouse hippocampal neuronal cultures 7 . Proper expression of neurotrophic factors in the skin is also crucial for guiding peripheral sensory innervation, as demonstrated by studies showing that overexpression of neurotrophin-4 in the epidermal basal cells of mice leads to abnormally increased innervation of the dermal footpad [8][9][10] .…”

Section: Introductionmentioning

confidence: 99%

Epidermal Collagen Reduction Drives Selective Aspects of Aging in Sensory Neurons

Krishna,

Waghmare,

Franitza

et al. 2024

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Despite significant progress in understanding the molecular processes of aging-associated neurodegeneration, the upstream mechanisms driving neuronal aging remain elusive. Here, we investigate the potential regulatory roles of non-neural tissues in neuronal aging, using Caenorhabditis elegans PVD polymodal neuron as a model. We find that cutaneous PVD neurons develop progressive excessive dendritic branching during normal aging, functionally correlated with age-related deficits in proprioception. Our study reveals that age-related reduction in skin collagens, a common change across species, triggers the aging process of PVD. Specifically, loss-of-function mutations or adulthood-specific RNAi knockdown of skin collagen genes,dpy-5orcol-120, which are downregulated with age, induce an early onset of PVD excessive dendritic branching and proprioception deficits. Overexpressingdpy-5orcol-120mitigates the development of excessive branching without affecting lifespan, suggesting a skin collagens′ role in promoting healthspan rather than longevity. Notably, neitherdpy-5orcol-120is not involved in aging-associated dendritic beading, another degenerative phenotype in PVD associated with harsh touch response deficits. Moreover,dpy-5mutation induces ectopic branching in ALM, but does not affect PLM, two other cutaneous sensory neurons. Finally, we identifyrig-3, a neuronal Immunoglobulin Superfamily member not expressed in PVD or the skin, functioning in the same pathway as skin collagen genes to preserve PVD neuron integrity during aging. Our findings reveal the causative role of age-related reduction in skin collagens in neuronal aging, selectively impacting distinct neuron subtypes and structures. This study underscores the importance of exploring multi-tissue strategies to comprehensively address the complexities of neuronal aging.

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“…Our preliminary exploratory work indicated that, through an in vitro cell culture research system, the "secreted protein mixture" from human-derived blood vessel smooth muscle cells (HBvSMCs) and primary mouse meningeal aSMCs has a nutritive effect on mouse hippocampal and cortical neurons. This is manifested by effectively promoting the developmental processes of neuronal dendrites and increasing neuronal survival rates [17].…”

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confidence: 99%

Netrin4 is a new target specific factor, ensuring adult sympathetic neuron survival via promoting protein synthesis

Zhu,

Zhou,

Wang

et al. 2023

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How mature neurons survive under homeostasis is a question of utmost importance and is known to be different from developing neurons. However, the understanding of this regard remains largely unknown. Here, based on the relationship between the sympathetic cervical ganglia (SCG) and the arterial networks of projecting and targeting organs, we report that the secretome of cerebral, but not peripheral, arterial smooth muscles (SMC) was required for the survival of sympathetic neurons. Among the secretome, we further identified that netrin-4, encoded by the ntn-4 gene, only entered neurons and not glia and played a crucial role both in vitro and in vivo. This was demonstrated with three independent lines of tamoxifen-inducible SMC-specific conditional knockout mice (cKO). Notably, in cKO mice, the local supply of exogenous netrin-4 confined to SCG selectively rescued neuronal necroptosis, which otherwise consistently occurred in a specific subgroup of SCG neurons that innervate cerebral SMCs. Mechanistically, we demonstrated that cerebral netrin-4 was endocytosed at the neurovascular interface and retrogradely long transported to peripheral soma in SCG, where it differentially regulated mRNA translations. This regulation suppressed vacuolization and neuronal necrosis, both of which took place spontaneously in cKO mice. The former is immediately followed by the latter when we injured axons using two-photon laser ablation. The findings revealed a new principle of neurovascular interactions vital for mature neuron survival, implying that under circumstances of cerebral SMC insufficient secretion, such as natural aging, may initiate mature neuronal loss due to uncontrolled vacuolization.

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Proteins secreted by brain arteriolar smooth muscle cells are instructive for neural development

Cited by 3 publications

References 40 publications

Local neurovascular coupling in the amygdala is responsible for context-dependent emotional adjustment

Local neurovascular coupling in the amygdala is responsible for context-dependent emotional adjustment

Epidermal Collagen Reduction Drives Selective Aspects of Aging in Sensory Neurons

Netrin4 is a new target specific factor, ensuring adult sympathetic neuron survival via promoting protein synthesis

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