ABSTRACT
Adult hippocampal neurogenesis is a remarkable form of brain plasticity through which new neurons are generated throughout life. Despite its important roles in cognition and emotion and its modulation in various preclinical disease models, the functional importance of adult hippocampal neurogenesis in human health has not been revealed because of a lack of tools for monitoring adult neurogenesis in vivo. Therefore, we performed an unbiased proteomics screen to identify novel proteins expressed during neuronal differentiation using a human neural stem cell model, and we identified the proteoglycan Glypican-2 (Gpc2) as a putative secreted marker of immature neurons. Exogenous Gpc2 binds to FGF2 and inhibits FGF2-induced neural progenitor cell proliferation. Gpc2 is enriched in neurogenic regions of the adult brain. Its expression is increased by physiological stimuli that increase hippocampal neurogenesis and decreased in transgenic models in which neurogenesis is selectively ablated. Changes in neurogenesis also result in changes in Gpc2 protein level in cerebrospinal fluid (CSF). Gpc2 is detectable in adult human CSF, and first pilot experiments with a longitudinal cohort indicate a decrease over time. Thus, Gpc2 may serve as a potential marker to monitor adult neurogenesis in both animal and human physiology and disease, warranting future studies.
Subject(s)
Adult Stem Cells/metabolism , Glypicans/cerebrospinal fluid , Hippocampus/metabolism , Neural Stem Cells/metabolism , Neurogenesis , Adult , Adult Stem Cells/cytology , Animals , Biomarkers/cerebrospinal fluid , Cell Differentiation , Cell Proliferation , Hippocampus/cytology , Humans , Male , Mice , Neural Stem Cells/cytologyABSTRACT
Melanin-concentrating hormone (MCH) is a hypothalamic neuropeptide that plays a role in the modulation of food intake and mood. In rodents, the actions of MCH are mediated via the MCHR1 receptor. The goal of this study was to investigate the effects of acute (1 h) and chronic (28 days) p.o. dosing of a novel MCHR1 antagonist, N-[3-(1-{[4-(3,4-difluorophenoxy)-phenyl]methyl}(4-piperidyl))-4-methylphenyl]-2-methylpropanamide (SNAP 94847), in three mouse models predictive of antidepressant/anxiolytic-like activity: novelty suppressed feeding (NSF) in 129S6/SvEvTac mice and light/dark paradigm (L/D) and forced swim test (FST) in BALB/cJ mice. A significant increase in the time spent in the light compartment of the L/D box was observed in response to acute and chronic treatment with SNAP 94847. An anxiolytic/antidepressant-like effect was found in the NSF test after acute and chronic treatment, whereas no effect was observed in the FST. Because neurogenesis in the dentate gyrus has been shown to be a requirement for the effects of antidepressants in the NSF test, we investigated whether neurogenesis was required for the effect of SNAP 94847. We showed that chronic treatment with SNAP 94847 stimulated proliferation of progenitors in the dentate gyrus. The efficacy of SNAP 94847 in the NSF test, however, was unaltered in mice in which neurogenesis was suppressed by X-irradiation. These results indicate that SNAP 94847 has a unique anxiolytic-like profile after both acute and chronic administration and that its mechanism of action is distinct from that of selective serotonin reuptake inhibitors and tricyclic antidepressants.
Subject(s)
Anti-Anxiety Agents , Antidepressive Agents , Anxiety/drug therapy , Hippocampus/drug effects , Piperidines/pharmacology , Receptors, Somatostatin/antagonists & inhibitors , Animals , Antidepressive Agents, Tricyclic/metabolism , Antimetabolites , Anxiety/psychology , Bromodeoxyuridine , Cell Line, Tumor , Cell Proliferation/drug effects , Citalopram/metabolism , Drug Evaluation, Preclinical , Feeding Behavior/drug effects , Hippocampus/cytology , Imipramine/metabolism , Immunohistochemistry , Male , Mice , Mice, Inbred BALB C , Motor Activity/drug effects , Neurons/drug effects , Selective Serotonin Reuptake Inhibitors/metabolism , X-RaysABSTRACT
Survey results on the subject of child abuse from the American Society of Dentistry for Children membership are reported. The survey results reflected the need of a documentation protocol for the dental office. A protocol is proposed which reviews the need of thorough assessment of orofacial lesions before concluding that child abuse exists. A data- and diagnostic-assessment form has been made using guidelines of the American Dental Association and other related referenced articles. The diagnostic-assessment form is presented to guide the practitioner through the documentation process and to develop a step-by-step decision on the probability of child abuse in any individual case.
