Studies of stroke damage at the molecular and cellular level
Office Phone: (608) 262-1709, (608) 263-3652
Our research focuses on mammalian brain, and almost all the work is done on the rodent hippocampal slice, which when removed from the brain still functions both electrophysiologically and biochemically. The hippocampus plays a critical role in memory formation, and is also the most susceptible area in the brain to changes in energy metabolism and to stroke. There are three major projects currently underway in the laboratory. In the first we are studying changes in protein synthesis at neuronal synapses in response to neural activity. This 'local' protein synthesis is thought to be a key step in memory formation. Electrical stimulation of the axons that make contact with the pyramidal cell dendrites greatly stimulates the synthesis of proteins in and near the spines. The current focus of work is on the complex biochemical mechanisms involved in this effect. The second area concerns brain damage in stroke and heart attacks. We have found that lysosomes are affected, liberating dangerous proteolytic enzymes and the current focus of work is on determining how energy deprivation leads to this 'permeabilization' of lysosomes to proteins. The third area is to understand the critical role of glucose in synaptic transmission. In particular, synaptic transmission fails in hippocampus when glycolysis is prevented, even though ATP levels are maintained by alternate substrates. We want to understand why this happens, and its implications for memory-related diseases.
- Chih, C.P., P. Lipton, and E.L. Jr. Roberts. 2001. Do active CNS really use lactate rather than glucose? Trends in Neurosciences 24: 573-578.
- Lipton, P. 1999. Ischemic cell death in brain neurons. Physiol. Rev. 79: 1431-1568.
- Zhang,Y. and P. Lipton. 1999. Cytosolic Ca2+ changes during in vitro ischemia in rat hippocampal slices: Major roles for glutamate and Na+-dependent Ca2+ release from mitochondria. J. Neurosci. 19: 3307-3315.
- Lytton, W.W. and P. Lipton. 1999. Can the hippocampus tell time? The temporo-septal engram shift model. NeuroReport 10: 2301-2306.
- Feig, S. and P. Lipton. 1993. Pairing the cholinergic agonist carbachol with patterned Schaffer collateral stimulation initiates protein syntheis in hippocampal CA1 pyramidal cell dendrites via a muscarinic, NMDA-dependent mechanism. J. Neurosci. 13: