title: St8sia2 deficiency plus juvenile cannabis exposure in mice synergistically affect higher cognition in adulthood.
abstract: The neural cell adhesion molecule (NCAM) and its functionally linked polysialyltransferases, ST8SIA2 and ST8SIA4, are crucial for synaptic plasticity. Variations in encoding genes have been associated with mental illness. Since cannabinoids can alter NCAM polysialylation, we hypothesized that delta-9-tetrahydrocannabinol (Δ9-THC) might act as environmental 'second hit' regarding cognition of St8sia2(-/-) mice. These mice show per se minor behavioral abnormalities, consisting of reduced anxiety and mild cognitive deficits. Chronic Δ9-THC treatment of juvenile male wildtype mice (St8sia2(+/+)) (7mg/kg every other day over 3 weeks) did not appreciably affect cognition. St8sia2(-/-) mice, however, displayed a synergistic negative consequence of Δ9-THC on learning/memory, accompanied by polysialic acid-free NCAM-180 reduction in hippocampus and polysialic acid increase in dentate outer molecular layer. These synergistic effects became obvious only months after the last Δ9-THC. We conclude that juvenile cannabis exposure may cause delayed but lasting damage on cognition in subjects genetically predisposed to altered NCAM polysialylation.
authors.affiliation: Clinical Neuroscience, Max Planck Institute of Experimental Medicine, Göttingen, Germany; DFG Research Center for Nanoscale Microscopy & Molecular Physiology of the Brain (CNMPB), Göttingen, Germany.
authors.forename: Martesa
authors.initials: M
authors.lastname: Tantra
authors.affiliation: Institute of Cellular Chemistry, Hannover Medical School, Hannover, Germany.
authors.forename: Tim
authors.initials: T
authors.lastname: Kröcher
authors.affiliation: Clinical Neuroscience, Max Planck Institute of Experimental Medicine, Göttingen, Germany; DFG Research Center for Nanoscale Microscopy & Molecular Physiology of the Brain (CNMPB), Göttingen, Germany.
authors.forename: Sergi
authors.initials: S
authors.lastname: Papiol
authors.affiliation: Clinical Neuroscience, Max Planck Institute of Experimental Medicine, Göttingen, Germany; DFG Research Center for Nanoscale Microscopy & Molecular Physiology of the Brain (CNMPB), Göttingen, Germany.
authors.forename: Daniela
authors.initials: D
authors.lastname: Winkler
authors.affiliation: Institute of Cellular Chemistry, Hannover Medical School, Hannover, Germany.
authors.forename: Iris
authors.initials: I
authors.lastname: Röckle
authors.affiliation: Clinical Neuroscience, Max Planck Institute of Experimental Medicine, Göttingen, Germany.
authors.forename: Jasmin
authors.initials: J
authors.lastname: Jatho
authors.affiliation: Institute of Cellular Chemistry, Hannover Medical School, Hannover, Germany.
authors.forename: Hannelore
authors.initials: H
authors.lastname: Burkhardt
authors.affiliation: Clinical Neuroscience, Max Planck Institute of Experimental Medicine, Göttingen, Germany.
authors.forename: Anja
authors.initials: A
authors.lastname: Ronnenberg
authors.affiliation: Institute of Cellular Chemistry, Hannover Medical School, Hannover, Germany.
authors.forename: Rita
authors.initials: R
authors.lastname: Gerardy-Schahn
authors.affiliation: Clinical Neuroscience, Max Planck Institute of Experimental Medicine, Göttingen, Germany; DFG Research Center for Nanoscale Microscopy & Molecular Physiology of the Brain (CNMPB), Göttingen, Germany. Electronic address: ehrenreich@em.mpg.de.
authors.forename: Hannelore
authors.initials: H
authors.lastname: Ehrenreich
authors.affiliation: Institute of Cellular Chemistry, Hannover Medical School, Hannover, Germany. Electronic address: hildebrandt.herbert@mh-hannover.de.
authors.forename: Herbert
authors.initials: H
authors.lastname: Hildebrandt
mesh_terms: D000367:Age Factors; D000818:Animals; D000831:Animals, Newborn; D001921:Brain / Q000187:drug effects / Q000378:metabolism; D015816:Cell Adhesion Molecules, Neuronal / Q000378:metabolism; D003072:Cognition Disorders / Q000139:chemically induced* / Q000235:genetics*; D004195:Disease Models, Animal; D004305:Dose-Response Relationship, Drug; D013759:Dronabinol / Q000633:toxicity*; D005786:Gene Expression Regulation / Q000187:drug effects / Q000235:genetics; D008297:Male; D018782:Maze Learning / Q000187:drug effects; D008568:Memory / Q000187:drug effects; D051379:Mice; D008810:Mice, Inbred C57BL; D008822:Mice, Transgenic; D011619:Psychotropic Drugs / Q000633:toxicity*; D012799:Sialyltransferases / Q000172:deficiency* / Q000235:genetics
chemical_list: D015816:Cell Adhesion Molecules, Neuronal; D011619:Psychotropic Drugs; D013759:Dronabinol; C046778:CMP-N-acetylneuraminate-poly-alpha-2,8-sialosyl sialyltransferase; D012799:Sialyltransferases
keywords: Learning index; NCAM; PolySia; Reference memory; Working memory; Δ-9-THC