Cortical cholinergic, glutamatergic and GABAergic terminals become upregulated during early stages of the transgenic amyloid pathology. Abundant evidence suggests that sAPP alpha, the product of the non-amyloidogenic alpha-secretase pathway, is neurotrophic both in vitro and when exogenously applied in vivo. The disintegrin metalloprotease ADAM-10 has been shown to have alpha-secretase activity in vivo. To determine whether sAPP alpha has an endogenous biological influence on cortical presynaptic boutons in vivo, we quantified cortical cholinergic, glutamatergic and GABAergic presynaptic bouton densities in either ADAM-10 moderate expressing (ADAM-10 mo) transgenic mice, which moderately overexpress ADAM-10, or age-matched non-transgenic controls. Both early and late ontogenic time points were investigated. ADAM-10 mo transgenic mice display significantly elevated cortical cholinergic, glutamatergic and GABAergic presynaptic bouton densities at the early time point (8 months). Only the cholinergic presynaptic bouton density remains significantly elevated in late-staged ADAM-10 mo transgenic animals (18 months). To confirm that the observed elevations were due to increased levels of endogenous murine sAPP alpha, exogenous human sAPP alpha was infused into the cortex of non-transgenic control animals for 1 week. Exogenous infusion of sAPP alpha led to significant elevations in the cholinergic, glutamatergic and GABAergic cortical presynaptic bouton populations. These results are the first to demonstrate an in vivo influence of ADAM-10 on neurotransmitter-specific cortical synaptic plasticity and further confirm the neurotrophic influence of sAPP alpha on cortical synaptogenesis.
Download full-text PDF |
Source |
|---|---|
| http://dx.doi.org/10.1016/j.neurobiolaging.2006.11.004 | DOI Listing |
Publication Analysis
Top Keywords
Similar Publications
Differential regulation of tissue-resident and blood-derived macrophages in models of autoimmune and traumatic peripheral nerve injury.
Front Immunol
December 2024
Department of Neurology, McGovern Medical School, The University of Texas Health Science Center at Houston, Houston, TX, United States.
Introduction: The current study focuses on understanding the functional role of different subsets of endoneurial macrophages in autoimmune polyneuropathies (AP) and traumatic peripheral nerve injury (TPNI), which holds potential for clinical application. Recent studies have advanced our understanding of the diverse origins of macrophages within peripheral nerves. However, there remains a gap in our knowledge regarding how endoneurial macrophages from different origins affect disease progression in AP versus TPNI.
View Article and Find Full Text PDFHigh levels of neurofilament light and YKL-40 in cerebrospinal fluid are related to poor outcome in ALS.
J Neurol Sci
August 2024
Department of Neurology, Institute of Clinical Neuroscience and Physiology, The Sahlgrenska Academy, University of Gothenburg, Gothenburg, Sweden. Electronic address:
Amyotrophic lateral sclerosis (ALS) is a neurological disease without effective treatment. No pathognomonic test can diagnose ALS in sporadic cases. Routine investigation in suspected cases includes neurological examination, imaging of the brain and spine and electromyography supported by blood and cerebrospinal fluid (CSF) analyses.
View Article and Find Full Text PDFAG1 Induces a Favorable Impact on Gut Microbial Structure and Functionality in the Simulator of Human Intestinal Microbial Ecosystem Model.
Curr Issues Mol Biol
January 2024
Research, Nutrition, and Innovation, Athletic Greens International, Carson City, NV 89701, USA.
Modulation of the human gut microbiome has become an area of interest in the nutraceutical space. We explored the effect of the novel foundational nutrition supplement AG1 on the composition of human microbiota in an in vitro experimental design. Employing the Simulator of Human Intestinal Microbial Ecosystem (SHIME) model, AG1 underwent digestion, absorption, and subsequent colonic microenvironment simulation under physiologically relevant conditions in healthy human fecal inocula.
View Article and Find Full Text PDFTriglyceride Lowering with Pemafibrate to Reduce Cardiovascular Risk.
N Engl J Med
November 2022
From the Center for Cardiovascular Disease Prevention, Division of Preventive Medicine (A.D.P., R.J.G., J.G.M., E.S.Z., B.M.E., N.P.P., J.E.B., P.M.R) and the Division of Cardiovascular Medicine (B.M.E.,P.L., P.M.R.), Brigham and Women's Hospital, the Division of Cardiovascular Medicine, Veteran Affairs Boston Health Care System (A.D.P., J.J.), and Kowa Pharma Development (R.O.) - all in Boston; University of Lille, Lille (J.-C.F.) and the Department of Neurology and Stroke Center, Paris Cité University, Paris (P.A.) - both in France; Kowa Research Institute, Morrisville, NC (S.E.C.); the Division of Lipidology, Department of Medicine, University of Cape Town, Cape Town, South Africa (D.J.B.); Utah Lipid Center, Salt Lake City (E.A.B.); the University of Colorado School of Medicine, Aurora (R.H.E.); the University of Tennessee Health Science Center, Memphis (M.B.E.); the Division of Endocrinology, Universitário Hospital João de Barros Barreto, Belém (J.S.F.), and the Heart Institute (InCor), University of São Paulo Medical School Hospital, and Hospital Israelita Albert Einstein (R.D.S.), São Paulo - all in Brazil; Columbia University Vagelos College of Physicians and Surgeons, New York (H.N.G.); Queen Giovanna University Hospital, Sofia, Bulgaria (A.G.); Jichi Medical University, Shimotsuke (S.I.), the Research Center for Advanced Science and Technology, University of Tokyo, Tokyo (T.K.), and Chiba University Graduate School of Medicine, Chiba (K.Y.) - all in Japan; Deutsches Herzzentrum München, Technische Universität München and German Center for Cardiovascular Research, Partner Site Munich Heart Alliance, Munich (W.K.), Institute of Epidemiology and Medical Biometry, University of Ulm, Ulm (W.K.), and Rheinisch-Westfälische Technische Hochschule Aachen, University Hospital Aachen, Aachen (N.M.) - all in Germany; McMaster University and Population Health Research Institute, Hamilton, ON (P.A.) and the Division of Endocrinology and Metabolism, St. Michael's Hospital, University of Toronto, Toronto (L.A.L.) - both in Canada; Docencia, Asistencia Médica e Investigación Clínica Medical Institute-Rusculleda Foundation for Research, Córdoba, Argentina (A.J.L.); Shupyk National Healthcare University of Ukraine, Kyiv (B.M.); Copenhagen University Hospital-Herlev Gentofte, University of Copenhagen, Copenhagen (B.G.N.); the Department of Medical Clinical Pharmacology, University of Debrecen, Debrecen, Hungary (D.P.); the Department of Primary Care and Public Health, Imperial College London, London (K.K.R.), and the Department of Endocrinology, Diabetes, and Metabolism, Manchester University Hospital NHS Foundation Trust, Manchester (H.S.) - both in the United Kingdom; the Russian Academy of Postgraduate Medical Education, Moscow (A.S.); and the Department of Cardiology and Structural Heart Diseases, Medical University of Silesia, Katowice, Poland (M.T.).
Background: High triglyceride levels are associated with increased cardiovascular risk, but whether reductions in these levels would lower the incidence of cardiovascular events is uncertain. Pemafibrate, a selective peroxisome proliferator-activated receptor α modulator, reduces triglyceride levels and improves other lipid levels.
Methods: In a multinational, double-blind, randomized, controlled trial, we assigned patients with type 2 diabetes, mild-to-moderate hypertriglyceridemia (triglyceride level, 200 to 499 mg per deciliter), and high-density lipoprotein (HDL) cholesterol levels of 40 mg per deciliter or lower to receive pemafibrate (0.
Want AI Summaries of new PubMed Abstracts delivered to your In-box?
Enter search terms and have AI summaries delivered each week - change queries or unsubscribe any time!