Professor Emeritus, Neuroscience
College of Medicine
Department of Neuroscience
Phone: 614-292-5660
Fax: 614-688-8742
cooke.1@osu.edu
Research Interests:
- Neural regulation of intestinal ion transport, coordination of intestinal peristalsis and secretion
- Gene expression of neural and epithelial receptors
- Interactions of the immune system with the enteric nervous system
Current Research: Approximately 9 liters of fluid enter the intestine daily, and less than 0.2 liters is excreted. The large transport capacity is attributed to epithelial cells, which have the ability to absorb or secrete ions and water. Normally, absorptive mechanisms predominate over secretory mechanisms. The balance is tipped from absorption to secretion when the intestine is exposed to noxious agents, enterotoxins or inflammatory mediators, many of which act on the enteric nervous system. The enteric nervous system — which is like a mini brain in the digestive tract — consists of two interconnecting neural plexuses containing myenteric and submucosal ganglia lying within the external muscle layers and the submucosa, respectively. Neurons in the submucosal ganglia regulate secretion and blood flow, while neurons in the myenteric ganglia are responsible for muscle contraction. Neurons within the plexuses are arranged in reflex circuits. Mapping the neural reflex circuits that are responsible for coordination of secretion and muscle contraction has been a focus of the current research program.
The immune system plays an important role in detecting foreign antigens in the lumen. Once activated, it can release inflammatory mediators that modulate neuronal activity. Some of these mediators — including histamine, prostaglandins and cytokines — activate neural alarm programs resulting in an outpouring of ions and water, resulting in diarrhea. These studies have relevance to food allergies that produce intestinal malaise and diarrhea. They are also relevant to inflammatory bowel diseases such as Crohn's disease and ulcerative colitis.
Many different approaches are being used to identify neural reflex circuits and their regulation by chemical mediators released by the immune system. Physiological and pharmacological experiments are directed at determining the specific neurotransmitters involved in neural reflexes activated either by physiological or pathophysiological stimuli. Measurement of chloride currents — as an indicator of secretion — is being used in conjunction with recordings from strain gauges attached to the muscle to examine the neural pathways involved in coordination of secretion and muscle contraction. Pharmacological agonists and antagonists in conjunction with ligand binding studies are being used to study the interaction of neurotransmitters with their receptors and their signaling mechanisms. Gene expression and regulation of neural and epithelial receptors in health and diseased states are being studied as well. Techniques used to understand the function of the enteric nervous system span from the molecular level to whole animal studies. These studies are expected to provide important insights into the enteric nervous system's role in health and in diarrheal states resulting from inflammatory bowel disease or food allergies.
Research Techniques:
- Molecular: Cell culture; mRNA and DNA isolation; cloning; reverse transcription-polymerase chain reaction; quantitative polymerase chain reaction; northern, southern and western analysis; DNA sequencing; bacterial transformations; and transfections
- Electrophysiological: Voltage-clamp techniques for identifying ionic currents, use of strain gauge amplifiers for measurement of muscle contraction
- Neurochemical: Ligand binding studies
- Other: Radioisotopic flux measurements, gel electrophoresis, immunohistochemistry, radioimmunoassay, enzyme immunoassay
Education:
PhD: The Ohio State University