VASOPRESSIN-INDUCED NEUROTROPHISM IN CULTURED HIPPOCAMPAL-NEURONS VIAV-1 RECEPTOR ACTIVATION

Structural enhancement of nerve cell morphology has been postulated to be an integral step in the cellular process leading to information st orage in the nervous system. To investigate this postulate, we determi ned whether vasopressin (AVP), a neural peptide that can enhance memor y function, would enhance the cytoarchitectural features of hippocampa l neurons in culture. Results of these studies demonstrated that in th e presence of serum, vasopressin (1 mu M), induced a significant incre ase in the number of neurites, in neuritic length, and in neurite diam eter following 48 h of exposure. Morphological complexity was also enh anced following vasopressin exposure as indicated by a significant inc rease in the number of filopodia/branches, in the sum of branch length s, and in the number of branch bifurcation points. The number of micro spikes decorating neuritic branches was also significantly increased f ollowing vasopressin exposure. To determine whether the neurotrophic e ffect of vasopressin was dependent upon factors present in serum, hipp ocampal nerve cells were cultured in serum-free media and exposed to 1 00-1000 nM AVP. Results of these studies demonstrated that in the abse nce of serum, AVP induced significant enhancement of hippocampal nerve cell growth and that the minimally effective concentration was reduce d from 1 Il M, as required in the presence serum, to 100 nM. In additi on, the time required for a significant increase in nerve cell growth to become apparent decreased from 48 to 24 h. These results demonstrat e that AVP-induced neurotrophism is not dependent upon unidentified fa ctors in serum. AVP-induced neurotrophism was found to be mediated by V, receptor activation. Significant enhancement of nerve cell growth o ccurred following exposure to V, receptor agonist (100-1000 nM), where as exposure to V, receptor agonist (100-1000 nM) did not increase any of the morphological parameters measured. Considered together, these d ata indicate that vasopressin can exert a significant neurotrophic eff ect upon hippocampal nerve cells in culture. Moreover, AVP-induced neu rotrophism is a direct effect and not dependent upon unidentified fact ors present in serum. Enhancement of hippocampal nerve cell growth occ urred in the presence of a specific V, receptor agonist and not follow ing exposure to a V, agonist, suggesting that activation of the phosph atidyl inositol pathway via V, receptor activation mediates AVP-induce d neurotrophism. Results of these studies are discussed with respect t o their implications for understanding vasopressin involvement during neural development and induction of cytoarchitectural modifications as sociated with memory formation. (C) 1991 John Wiley and Sons, Inc.