Research in my laboratory in broadly focused on excitatory neurotransmitters and neurotoxicity in both the developing and mature CNS. Work in the adult CNS has mainly been focused on the derangements that occur in the CNS as a result of the NMDA glutamate system being rendered hypofunctional by NMDA antagonists. Hypofuntion of this system in adulthood has been tied to several neuropsychiatric conditions such as schizophrenia, Alzheimer’s disease and bipolar disorder. In the developing CNS a wide range of agents (e.g. NMDA antagonists, GABAmimetics, anticonvulsants, ethanol, magnesium, and lead) can produce massive apoptotic degeneration during a specific time limited period (human equivalent = last trimester of gestation to first several years of postnatal life). Animals exposed briefly to such agents have been found to have enduring cognitive and behavioral deficits. Recently, we have been studying the ability of solvents (e.g. DMSO, propylene glycol, straight chained alcohols) to also produce apoptosis in the developing CNS. Most of the work involves rodents and non-human primates and is histological and neurotoxicological in nature, but in collaboration with others we are also studying the enduring behavioral and cognitive consequences of this exposure. Results from our studies have direct application to clinical practice because most of these agents are in clinical use (e.g. ketamine, nitrous oxide [a.k.a., laughing gas], isoflurane, benzodiazepines, barbiturates, propylene glycol) or are abused (e.g. phencyclidine, ethanol). In addition, because inducing developmental apoptosis by some of these agents likely results in depressing the NMDA receptor system, these developmental injuries might also be involved in the subsequent development of schizophrenia, Alzheimer’s disease and bipolar disorder.
Research Publications
Farber NB (2003 Nov). The NMDA receptor hypofunction model of psychosis. Ann N Y Acad Sci. 1003: 119-30. Full Article >
Farber NB, Nemmers B, Noguchi KK (2006 Sep 15). Acute D2/D3 dopaminergic agonism but chronic D2/D3 antagonism prevents NMDA antagonist neurotoxicity. Biol Psychiatry. 60 (6): 630-8. Full Article >
Farber NB, Jiang X, Dikranian K, Nemmers B (2003 Dec 12). Muscimol prevents NMDA antagonist neurotoxicity by activating GABAA receptors in several brain regions. Brain Res. 993 (1-2): 90-100. Full Article >
Creeley CE, Wozniak DF, Nardi A, Farber NB, Olney JW (2006 Nov 15). Donepezil markedly potentiates memantine neurotoxicity in the adult rat brain. Neurobiol Aging. Full Article >
Farber NB, Olney JW (2003 Dec 30). Drugs of abuse that cause developing neurons to commit suicide. Brain Res Dev Brain Res. 147 (1-2): 37-45. Full Article >
Olney JW, Wozniak DF, Jevtovic-Todorovic V, Farber NB, Bittigau P, Ikonomidou C (2002 Jun). Glutamate and GABA receptor dysfunction in the fetal alcohol syndrome. Neurotox Res. 4 (4): 315-25. Full Article >
Contact Info
Nuri Farber, M.D.
Office Location: 4410 Renard
Office Phone: 314-362-2462
Lab Phone: 314-362-2479
Other Phone: 314-362-2460
Campus Box: 8134
Fax: 314-362-9902
farbern@psychiatry.wustl.edu
