The cerebrospinal fluid: regulator of neurogenesis, behavior, and beyond
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Cellular and Molecular Life Sciences
REVIEW
The cerebrospinal fluid: regulator of neurogenesis, behavior, and beyond Mauro W. Zappaterra • Maria K. Lehtinen
Received: 31 December 2011 / Revised: 28 February 2012 / Accepted: 1 March 2012 / Published online: 14 March 2012 Ó Springer Basel AG 2012
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. Keywords Cerebrospinal fluid Choroid plexus Neurogenesis Traumatic brain injury Abbreviations BDNF Brain-derived neurotrophic factor BMI Body mass index BMP Bone morphogenetic protein Bmpr1a BMP receptor 1a
M. W. Zappaterra Department of Physical Medicine and Rehabilitation, VA Greater Los Angeles Healthcare System, 11301 Wilshire Blvd, Los Angeles, CA 90073, USA e-mail: [email protected] M. K. Lehtinen (&) Department of Pathology, Children’s Hospital Boston, Harvard Medical School, 300 Longwood Avenue, Boston, MA 02115, USA e-mail: [email protected]
BrdU CNS ChP CSF DG ELISA ERK1/2 Ecrg4 FGF GDF GDNF IGF IGF1R IGFBPs Irs2 LIF Lmx1a LV MS NEP NGF NT-3 Pdk1 PEDF Pten RA Rhomb sAPP Shh SCN SVZ Tel TGF TNF TBI
Bromodeoxyuridine Central nervous system Choroid plexus Cerebrospinal fluid Dentate gyrus Enzyme-linked immunosorbent assay Extracellular signal-regulated kinase 1/2 Esophageal cancer-related gene-4 Fibroblast growth factors Growth differentiation factors Glial-derived neurotrophic factor Insulin-like growth factors IGF1 receptor IGF-binding proteins Insulin receptor substrate 2 Leukemia inhibiting factor LIM homeobox transcription factor 1, alpha Lateral ventricle Mass spectrometry Neuroepithelium Nerve growth factor Neurotrophin 3 Phosphoinositide-dependent kinase-1 Pigment epithelial derived factor Phosphatase and tensin homolog Retinoic acid Rhombencephalon Soluble amyloid precursor protein Sonic hedgehog Suprachiasmatic nucleus Subventricular zone Telencephalon Transforming growth factor Tumor necrosis factor Traumatic brain injury
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V VEGF VZ Wnt1
M. W. Zappaterra, M. K. Lehtinen
Ventricle Vascular endothelial growth factor Ventricular zone Wingless-type MMTV integration site family, member 1
Introduction The cerebrospinal fluid (CSF) has intrigued scientists, physicians, and philosophers for close to 4,000 years. The ear
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