This volume provides a comprehensive update on basic glutamate research, from a clinical perspective. Thus, emphasis is placed on how the different molecular players at the glutamate synapse interact to produce a postsynaptic response, how synaptic transmission is perturbed in epilepsy and other pathological conditions, and how glutamate may acquire toxic properties and lead to acute or chronic neurodegeneration. Promising targets for therapeutic strategies are discussed.
A coherent picture is provided of the glutamate synapse and its molecular organization. The book therefore deals with each step in the signal process, from synthesis and vesicular uptake of glutamate to its clearance following receptor activation.
The Glutamate Synapse as a Therapeutic Target, 1st Edition
I. Glutamate Release and Transport.
1. Calcium channels coupled to glutamate release (T.J. Turner). 2. Presynaptic modulation of glutamate release ( D.G. Nicholls). 3. Properties and localization of glutamate transporters (N.C. Danbolt, F.A. Chaudhry, Y. Dehnes, K.P. Lehre, K. Ullensvang, J. Storm-Mathisen). 4. Physiological and pathological operation of glutamate transporters (B. Billups, D. Rossi, T. Oshima, O. Warr, M. Takahashi, M. Sarantis, M. Szatkowski, D. Attwell). 5. Control of the time course of glutamatergic synaptic currents (L. Trussell). II. Glutamate Synthesis and Translocation to Vesicles.
6. Synthesis of glutamate and its regulation (E. Kvamme). 7. Uptake of glutamate into synaptic vesicles (F. Fonnum, E.M. Fykse, S. Roseth). III. Glutamate Receptors.
8. Synaptic arrangement of glutamate receptors (Y. Takumi, L. Bergersen, A.S. Landsend, E. Rinvik, O.P. Ottersen). 9. Anchoring of glutamate receptors at the synapse (Y.-P. Hsueh, M. Sheng). 10. The organization and regulation of non-NMDA receptors in neurons (R.J. Wenthold, K.W. Roche). 11. AMPA receptors: molecular and functional diversity (K. Borges, R. Dingledine). 12. Molecular determinants of NMDA receptor pharmacological diversity (D.T. Monaghan, V.J. Andaloro, D.A. Skifter). 13. Modulation of NMDA receptors (J.F. MacDonald, X.-G. Xiong, W.-Y. Lu, R. Raouf, B.A. Orser). 14. Metabotropic glutamate receptors and neurodegeneration (V. Bruno, G. Battaglia, A. Copani, G. Casabona, M. Storto, V. De Giorgi Cerevini, R. Ngomba, F. Nicoletti). IV. Glutamate Toxicity and Cell Death in the Cental Nervous System.
15. Intracellular calcium and magnesium: critical determinants of excitotoxicity? (I.J. Reynolds). 16. Neurodegeneration and glutamate induced oxidative stress (N. Nakao, P. Brundin). 17. Glutamate induced cell death: apoptosis or necrosis? (M. Ankarcrona). 18. Synaptic plasticity in ischemia: Role of NMDA receptors (V. Crépel, P. Congar, L. Aniksztejn, H. Gozlan, C. Hammond, Y. Ben-Ari). 19. Glutamate in the human brain: possible roles in synaptic transmission and ischemia (J. Berg-Johnsen, T.S. Haugstad, I.A. Langmoen). 20. Glutamate and its receptors in the pathophysiology of brain and spinal cord injuries (B. Alessandri, R. Bullock). 21. Glutamate toxicity in chronic neurodegenerative disease (E. Lancelot, M. Flint Beal). V. Conditions of Perturbed Glutamatergic Transmission.
22. Electrophysiological substrates for focal epilepsies (J.G.R. Jefferys, R.D. Traub). 23. Involvement of glutamate in human epileptic activities (R.D. Scheyer). 24. Glutamate receptors in epilepsy (A. Chapman). 25. Effects of antiepileptic drugs on the activation of glutamate receptors (E. Taubøll, L. Gjerstad). 26. Antiepileptic drug treatment: clinical considerations and concerns (E. Brodtkorb). 27. The glutamate synapse: a target in the pharmacological management of hyperalgesic pain states (M.O. Urban, G.F. Gebhart). 28. The glutamate synapse in neuropsychiatric disorders: focus on schizophrenia and Alzheimer's disease (N.B. Farber, J.W. Newcomer, J.W. Olney). VI. Perspectives.
29. The glutamate synapse as a therapeutical target: perspectives for the future (B. Meldrum).