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Transient Receptor Potential Vanilloid 4: a Double-Edged Sword in the Central Nervous System

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Abstract

Transient receptor potential vanilloid 4 (TRPV4) is a nonselective cation channel that can be activated by diverse stimuli, such as heat, mechanical force, hypo-osmolarity, and arachidonic acid metabolites. TRPV4 is widely expressed in the central nervous system (CNS) and participates in many significant physiological processes. However, accumulative evidence has suggested that deficiency, abnormal expression or distribution, and overactivation of TRPV4 are involved in pathological processes of multiple neurological diseases. Here, we review the latest studies concerning the known features of this channel, including its expression, structure, and its physiological and pathological roles in the CNS, proposing an emerging therapeutic strategy for CNS diseases.

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Abbreviations

TRPV4:

Transient receptor potential vanilloid 4

VR-OAC:

Vanilloid receptor-related osmotically activated channel

CNS:

Central nervous system

TRP:

Transient receptor potential

AA:

Arachidonic acid

4α-PDD:

4α-Phorbol 12, 13-didecanoate

ARDs:

Ankyrin repeat domains

Src:

Proto-oncogene tyrosine-protein kinase

Pacsin3:

Protein kinase C and casein kinase substrate in neurons protein 3

AIP4:

Atrophin-interacting protein 4

MAP7:

Microtubule-associated protein-7

MS:

Multiple sclerosis

AD:

Alzheimer’s disease

EAE:

Experimental autoimmune encephalomyelitis

OVLT:

Organum vasculosum of the lamina terminalis

SFO:

Subfornical organ

SON:

Supraoptic nucleus

PVN:

Paraventricular nucleus

AVP:

Arginine vasopressin

RVD:

Regulatory volume decrease

CPECs:

Choroid plexus epithelial cells

ANO1:

Anoctamin 1

BCECs:

Brain capillary endothelial cells

BBB:

Blood-brain barrier

PO/AH:

Preoptic area/anterior hypothalamus

MNCs:

Magnocellular neurosecretory cells

RMP:

Resting membrane potential

APs:

Action potentials

BCSFB:

Blood cerebrospinal fluid barrier

TBI:

Traumatic brain injury

MCAO:

Middle cerebral artery occlusion

ICH:

Intracerebral hemorrhage

ZO-1:

Zonula occludens-1

MMP-2/9:

Matrix metalloproteinases-2/9

A2M:

α-2-macroglobulin

CSF:

Cerebrospinal fluid

NVC:

Neurovascular coupling

CBF:

Cerebral blood flow

IP3Rs:

Inositol trisphosphate receptors

GqPCRs:

Gq-protein-coupled receptors

PLC:

Phospholipase C

NO:

Nitric oxide

EDHF:

Endothelium-derived hyperpolarizing factor

aECs:

Arteriolar endothelial cells

SMCs:

Smooth muscle cells

eNOS:

Endothelial NO synthase

FCD:

Focal cortical dysplasia

TSC:

Tuberous sclerosis complex

GFAP:

Glial fibrillary acidic protein

PKC:

Protein kinase C

NMDA:

N-methyl-D-aspartate

AMPA:

α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid

GABA:

γ-aminobutyric acid

IGABA :

γ-aminobutyric acid-activated current

AMPK:

AMP-activated protein kinase

PI3K/Akt:

Phosphatidyl inositol 3 kinase protein kinase B

PISE:

Pilocarpine-induced status epilepticus

IK :

Delayed rectifier current

KCHIP2:

K+ channel interacting protein 2

IA :

Rapidly inactivating potassium current

NLRP3:

Nucleotide-binding oligomerization domain-like receptor pyrin domain containing 3

MCAO:

Middle cerebral artery occlusion

INMDA :

NMDA-activated current

p38 MAPK:

p38 mitogen-activated protein kinase

Aβ:

Amyloid β

SMA:

Spinal muscular atrophy

EMT:

Epithelial-mesenchymal transformation

Rac1:

Ras-related C3 botulinum toxin substrate 1

ECM:

Extracellular matrix

Cdc42:

Cell division cycle 42

N‑wasp:

Neural Wiskott–Aldrich syndrome proteins

CaMKII:

Calmodulin-dependent protein kinase II

FADD:

Fas-associated protein with death domain

ECs:

Endothelial cells

E-cad:

E‐cadherin

N-cad:

N‐cadherin

α‐SMA:

α‐smooth muscle actin

YAP/TAZ:

Yes-associated protein/transcriptional coactivator with PDZ

ROCK1:

Rho-associated protein kinase

VEGF:

Vascular endothelial growth factor

IFN- ɣ:

Interferon-ɣ

TBI:

Traumatic brain injury

SCI:

Spinal cord injury

CBD:

Cannabidiol

ENS:

Excitatory neurotransmitter system

INS:

Inhibitory neurotransmitter system

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Acknowledgements

We appreciate Xiang-lei Jia and Xue-lei Cheng for their valuable comments.

Funding

This research is supported by the Natural Science Foundation of China (Grant No. 82171452, No. 82060588), the Translational Medicine and Interdisciplinary Research Joint Fund of Zhongnan Hospital of Wuhan University (Grant No. ZNLH201909), the Medical Science Advancement Program of Wuhan University (No. TFJC2018001, TFLC2018001).

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  1. Department of Physiology, Hubei Provincial Key Laboratory of Developmentally Originated Disease, Taikang Medical School (School of Basic Medical Sciences), Wuhan University, Donghu Rd185#, Wuhan, 430071, Hubei, China

    Meng-liu Zeng, Shuo Kong, Tao-xiang Chen & Bi-wen Peng

  2. Medical Science Research Center, Zhongnan Hospital of Wuhan University, Wuhan, 430071, China

    Meng-liu Zeng

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  1. Meng-liu Zeng
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  2. Shuo Kong
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All authors contributed to the study conception and design. The first draft of the manuscript was written by Meng-liu Zeng, and all authors commented on previous versions of the manuscript. All authors read and approved the final manuscript.

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Correspondence to Bi-wen Peng.

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Zeng, Ml., Kong, S., Chen, Tx. et al. Transient Receptor Potential Vanilloid 4: a Double-Edged Sword in the Central Nervous System. Mol Neurobiol 60, 1232–1249 (2023). https://doi.org/10.1007/s12035-022-03141-6

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