A unifying theme of my research is the mechanisms of neurotransmitter release and reuptake and their alterations by drugs and disease.
Previous research in collaboration with Dr. Bernardino Ghetti and Dr. Jay R. Simon involved the dopaminergic nigrostriatal neurons of the Weaver Mutant Mouse. The homozygous Weaver has a loss of about 70% of these neurons which are the same neurons that degenerate in Parkinson's disease in humans. In our work we have found that the remaining neurons compensate by releasing a larger fraction of their nerve terminal contents of dopamine in response to certain stimuli including amphetamine. They also have a lower than normal ability to recapture the released dopamine by reuptake. These changes are in the direction of reversing the dopaminergic neuron deficit.
More recently my research concerned the mechanisms for the pain of painful diabetic neuropathy. We made rats diabetic with STZ -a toxin which destroys the pancreatic beta cells. We then selected the diabetic rats that become allodynic -that is they respond to a normally non-painful mechanical stimulus as though it were painful. We examined the release of the transmitters of the primary afferent neurons which synapses in the spinal cord -Substance P, another peptide CGRP and the excitatory amino acid transmitter glutamate -to determine if the release is increased in tissue from diabetic rats with allodynia. We are also looking at the effect of high glucose conditions in vitro on cultures of the primary afferent neurons.
Currently we are concentrating on the mechanisms and modulation of glutamate release from the sensory neurons. The mechanism for capsaicin stimulated glutamate release seems to be different than that for the peptides. This opens the possibility that the regulation of glutamate release by various second messengers may be different also.
Measurement of transmitter release from spinal cord or hippocampus (or other brain regions) slices or from neurons in culture (particularaly sensory neurons). Glutamate measured by HPLC-EC detection of OPA derivatives. CGRP and SP measured by RIA.
Enzymes, Glutamate, Nervous System, Neurological Disorders, Neuropharmacology, Neuroscience, Neurotransmitters, Pain, Pharmacology, Receptors, Sensory Neurons
