title: Enzymatic removal of polysialic acid from neural cell adhesion molecule interrupts gonadotropin releasing hormone (GnRH) neuron-glial remodeling.
abstract: There is abundant evidence to prove that the astrocytes are highly dynamic cell type in CNS and under physiological conditions such as reproduction, these cells display a remarkable structural plasticity especially at the level of their distal processes ensheathing the gonadotropin releasing hormone (GnRH) axon terminals. The morphology of GnRH axon terminals and astrocytes in the median eminence region of hypothalamus show activity dependent structural plasticity during different phases of estrous cycle. In the current study, we have assessed the functional contribution of ∞-2,8-linked polysialic acid (PSA) on neural cell adhesion molecule (PSA-NCAM) in this neuronal-glial plasticity using both in vitro and in vivo model systems. In vivo experiments were carried out after stereotaxic injection of endoneuraminidase enzyme (endo-N) near median eminence region of hypothalamus to specifically remove PSA residues on NCAM followed by localization of GnRH, PSA-NCAM and glial fibrillary acidic protein (GFAP) by immunostaining. Using in vitro model, structural remodeling of GnV-3 cells, (a conditionally immortalized GnRH cell line) co-cultured with primary astrocytes was studied after treating the cells with endo-N. Marked morphological changes were observed in GnRH axon terminals in proestrous phase rats and control GnV-3 cells as compared to endo-N treatment i.e. after removal of PSA. The specificity of endo-N treatment was also confirmed by studying the expression of PSA-NCAM by Western blotting in cultures treated with and without endo-N. Removal of PSA from surfaces with endo-N prevented stimulation associated remodeling of GnRH axon terminals as well as their associated glial cells under both in vivo and in vitro conditions. The current data confirms the permissive role of PSA to promote dynamic remodeling of GnRH axon terminals and their associated glia during reproductive cycle in rats.
authors.affiliation: Department of Biotechnology, Guru Nanak Dev University, Amritsar 143005, India.
authors.forename: Sushil
authors.initials: S
authors.lastname: Kumar
authors.forename: Jyoti
authors.initials: J
authors.lastname: Parkash
authors.forename: Hardeep
authors.initials: H
authors.lastname: Kataria
authors.forename: Gurcharan
authors.initials: G
authors.lastname: Kaur
mesh_terms: D000818:Animals; D001253:Astrocytes / Q000378:metabolism; D002478:Cells, Cultured; D018920:Coculture Techniques; D030762:Estrous Cycle; D005260:Female; D005904:Glial Fibrillary Acidic Protein / Q000378:metabolism; D006026:Glycoside Hydrolases / Q000008:administration & dosage / Q000494:pharmacology*; D007987:Gonadotropin-Releasing Hormone / Q000378:metabolism / Q000502:physiology*; D007031:Hypothalamus / Q000166:cytology / Q000187:drug effects / Q000378:metabolism; D008845:Microinjections; D019006:Neural Cell Adhesion Molecules / Q000378:metabolism* / Q000502:physiology; D009457:Neuroglia / Q000166:cytology / Q000187:drug effects / Q000502:physiology*; D009473:Neuronal Plasticity; D009474:Neurons / Q000166:cytology / Q000187:drug effects / Q000502:physiology*; D051381:Rats; D017207:Rats, Sprague-Dawley; D017208:Rats, Wistar; D012794:Sialic Acids / Q000378:metabolism*
chemical_list: D005904:Glial Fibrillary Acidic Protein; D019006:Neural Cell Adhesion Molecules; D012794:Sialic Acids; C021319:polysialic acid; D007987:Gonadotropin-Releasing Hormone; D006026:Glycoside Hydrolases; C090534:endo-alpha-sialidase