The difference between controls and chronically MK-801-injected rats is highly significant as calculated with the post-hoc Scheffe test. Discussion The cellular model of glutamatergic dysfunction presented here is based on the smallest ATPase inhibitor cortical network loop, the local inhibitory feedback circuit. We demonstrated in vitro that both recurrent inhibition and its LTP can be selectively inhibited by low doses of NMDA antagonists. The nature of this differential sensitivity of NMDA receptors is still unclear, but may be related to the different Inhibitors,research,lifescience,medical subunit assembly of NMDA receptors on

interneurons compared with pyramidal cells,28 which also has consequences on the expression of NMDA-gated currents.29 Selective impairment of local inhibition may lead to increased excitability-

of the cortical network, causing intrinsic excitotoxic damage with greatest vulnerability of PV[+] interneurons, and to functional impairment, which may also include higher cognitive functions as learning and recall, Inhibitors,research,lifescience,medical as demonstrated in the computer model. Lack of synchronization of the cortical input onto mesolimbic cells may lead to a relative Inhibitors,research,lifescience,medical hyperfunction of the dopaminergic modulation of these cells, with consecutive impairment of the thalamic filter. Consistent with schizophrenia, we also demonstrated that the vulnerability of NMDA-mediated recurrent inhibition may be most pronounced in adolescent animals and male animals, whereas female sex steroids mayhave a protective effect. In conclusion, this model supplies a glutamatergic basis of schizophrenia. The next step Inhibitors,research,lifescience,medical is now to examine its modulation by other neurotransmitters implicated in schizophrenia, such as serotonin and dopamine. Selected abbreviations and acronyms AMPA amino-3-hydroxy-5-methil-4-isoxazole

propionic acid APV 2-ammo-5-phosphovaleric acid DAPI 4′.6-diamidino-2-phenylindole DNQX 6,7-dinitroquinoxaline-2,3-dione EAA excitatory amino acid EPSP excitatory postsynaptic potential GABA γ-aminobutyric acid IPSP inhibitory postsynaptic potential LTP long-term potentiation Inhibitors,research,lifescience,medical NAAG N-acetyl-L-aspartyl-L-glutamic acid NMDA N-methyl-D-aspartate PCP phencyclidine PTP posttetanic potentiation Notes This work was supported by grants from the Department of Veterans Affairs and the Deutsche Forschungsgemeinschaft (GR 1264/2-2, 7-1 and 8-1).
Because the prevalence of Alzheimer’s disease (AD) is age-dependent and the number of the oldest old is rising, mafosfamide the cost of this disease will increase considerably in the forthcoming decades, without obvious sources to fund it. This is true in the western world where the ratio of working force/retirees is decreasing,1 as well as the third world where progress in health care has raised the life expectancy. Studies of AD cost, conducted over the last decade have produced discrepant results, a fact that has not prevented interested parties (consumers, providers, and government agencies) to use the results to advance their respective, at times opposed, agendas.