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The cerebrospinal fluid: regulator of neurogenesis, behavior, and beyond

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Abstract

The cerebrospinal fluid (CSF) has attracted renewed interest as an active signaling milieu that regulates brain development, homeostasis, and disease. Advances in proteomics research have enabled an improved characterization of the CSF from development through adulthood, and key neurogenic signaling pathways that are transmitted via the CSF are now being elucidated. Due to its immediate contact with neural stem cells in the developing and adult brain, the CSF’s ability to swiftly distribute signals across vast distances in the central nervous system is opening avenues to novel and exciting therapeutic approaches. In this review, we will discuss the development of the choroid plexus-CSF system, and review the current literature on how the CSF actively regulates mammalian brain development, behavior, and responses to traumatic brain injury.

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Abbreviations

BDNF:

Brain-derived neurotrophic factor

BMI:

Body mass index

BMP:

Bone morphogenetic protein

Bmpr1a:

BMP receptor 1a

BrdU:

Bromodeoxyuridine

CNS:

Central nervous system

ChP:

Choroid plexus

CSF:

Cerebrospinal fluid

DG:

Dentate gyrus

ELISA:

Enzyme-linked immunosorbent assay

ERK1/2:

Extracellular signal-regulated kinase 1/2

Ecrg4:

Esophageal cancer-related gene-4

FGF:

Fibroblast growth factors

GDF:

Growth differentiation factors

GDNF:

Glial-derived neurotrophic factor

IGF:

Insulin-like growth factors

IGF1R:

IGF1 receptor

IGFBPs:

IGF-binding proteins

Irs2:

Insulin receptor substrate 2

LIF:

Leukemia inhibiting factor

Lmx1a:

LIM homeobox transcription factor 1, alpha

LV:

Lateral ventricle

MS:

Mass spectrometry

NEP:

Neuroepithelium

NGF:

Nerve growth factor

NT-3:

Neurotrophin 3

Pdk1:

Phosphoinositide-dependent kinase-1

PEDF:

Pigment epithelial derived factor

Pten:

Phosphatase and tensin homolog

RA:

Retinoic acid

Rhomb:

Rhombencephalon

sAPP:

Soluble amyloid precursor protein

Shh:

Sonic hedgehog

SCN:

Suprachiasmatic nucleus

SVZ:

Subventricular zone

Tel:

Telencephalon

TGF:

Transforming growth factor

TNF:

Tumor necrosis factor

TBI:

Traumatic brain injury

V:

Ventricle

VEGF:

Vascular endothelial growth factor

VZ:

Ventricular zone

Wnt1:

Wingless-type MMTV integration site family, member 1

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Acknowledgments

We thank V. Ho and A. Malesz for critical reading of this manuscript. We are grateful for support from the Eleanor and Miles Shore Fellowship Program for Scholars in Medicine/Children’s Hospital Boston Career Development Award, and the NIH (Award number R00 NS072192). M.K.L. is an Alfred P. Sloan Research Fellow.

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  1. Department of Physical Medicine and Rehabilitation, VA Greater Los Angeles Healthcare System, 11301 Wilshire Blvd, Los Angeles, CA, 90073, USA

    Mauro W. Zappaterra

  2. Department of Pathology, Children’s Hospital Boston, Harvard Medical School, 300 Longwood Avenue, Boston, MA, 02115, USA

    Maria K. Lehtinen

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Zappaterra, M.W., Lehtinen, M.K. The cerebrospinal fluid: regulator of neurogenesis, behavior, and beyond. Cell. Mol. Life Sci. 69, 2863–2878 (2012). https://doi.org/10.1007/s00018-012-0957-x

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