FGF-2-responsive neural stem cell proliferation requires CCg, a novel autocrine/paracrine cofactor.

Laboratory of Genetics, The Salk Institute, La Jolla, California 92037, USA.
Neuron (Impact Factor: 15.98). 12/2000; 28(2):385-97. DOI: 10.1016/S0896-6273(00)00119-7
Source: PubMed

ABSTRACT We have purified and characterized a factor, from the conditioned medium of neural stem cell cultures, which is required for fibroblast growth factor 2's (FGF-2) mitogenic activity on neural stem cells. This autocrine/paracrine cofactor is a glycosylated form of cystatin C (CCg), whose N-glycosylation is required for its activity. We further demonstrated that, both in vitro and in vivo, neural stem cells undergoing cell division are immunopositive for cystatin C. Finally, we showed in vivo functional activity of CCg by demonstrating that the combined delivery of FGF-2 and CCg to the adult dentate gyrus stimulated neurogenesis. We propose that the process of neurogenesis is controlled by the cooperation between trophic factors and autocrine/paracrine cofactors, of which CCg is a prototype.

  • [Show abstract] [Hide abstract]
    ABSTRACT: To investigate the changes of cerebrospinal fluid (CSF) cystatin C (CC) levels associated with the postoperative ischemic conditions and prognostic outcome in patients with aneurysmal subarachnoid hemorrhage (SAH). MATERIAL and
    Turkish neurosurgery. 01/2014; 24(3):391-7.
  • [Show abstract] [Hide abstract]
    ABSTRACT: Alcohol dehydrogenase 5 (ADH5) is a widely conserved enzyme for alcohol and aldehyde metabolism in mammals. Despite dynamic expression throughout neurogenesis, its role in neuronal development remains unknown. Here we present the first evidence that ADH5 is a negative regulator of neuronal differentiation. Gene expression analyses identify a constant reduction of ADH5 levels throughout neuronal development. Overexpression of ADH5 reduces both development and adult neuronal differentiation of mouse neurons. This effect depends on the catalytic activity of ADH5 and involves ADH5 mediated denitrosation of histone deacetylase 2 (HDAC2). Our results indicate that ADH5 counteracts neuronal differentiation of human neural stem cells, and that this effect can be reversed by pharmacological inhibition of ADH5. Based on these observations, we propose that ADH5 is a novel suppressor of neuronal differentiation and maturation. Inhibition of ADH5 may improve adult neurogenesis in a physiological or pathological setting.
    Journal of Biological Chemistry 06/2014; · 4.60 Impact Factor
  • [Show abstract] [Hide abstract]
    ABSTRACT: Adult hippocampal neurogenesis (AHN) is involved in learning, memory, and stress, and plays a significant role in neurodegenerative and psychiatric disorders. As an age-dependent process, AHN is largely influenced by changes that occur during the pre- and postnatal stages of brain development, and constitutes an important field of research. This review examines the current knowledge regarding the regulators of AHN and the influence of prenatal and postnatal stress on later AHN. In addition, a hypothesis is presented suggesting that each kind of stress influences a specific neurogenic pool, developmental or postnatal, that later becomes a precursor with important repercussions for AHN. This hypothesis is referred to as "the double neurogenic pool hypothesis." Discovering what receptors, transcription factors, or genes are specifically activated by different stressors is proposed as an essential line of future research in the field. Such knowledge shall constitute an important starting point towards the goal of modifying AHN in neurodegenerative or psychiatric diseases. Copyright © 2014 Elsevier B.V. All rights reserved.
    Behavioural Brain Research 12/2014; 281. · 3.39 Impact Factor