The primary focus of the Mitchell laboratory concerns fundamental mechanisms of plasticity in respiratory motor control. Several experimental models have been developed to study respiratory plasticity utilizing diverse experimental approaches, including: neurophysiological studies in vivo and in vitro, neuroanatomical and neurochemical studies, cell/molecular investigations including the first use of RNA interference in the mammalian nervous system in vivo, and studies of ventilation in unanesthetized animals.
Areas currently receiving major funding include (active collaborators are indicated in parentheses):
Brainstem and spinal plasticity induced by intermittent hypoxia
- Spinal, serotonin-dependent long-term facilitation following acute, hypoxic episodes.
- Roles of BDNF, kinases, phosphatases and ROS in respiratory long-term facilitation (Watters, Baker-Herman)
- Plasticity elicited by chronic intermittent hypoxia (Olson, Svaren)
- Age, gender and genetic influences on respiratory plasticity (Behan)
Respiratory plasticity and functional recovery following spinal injury (MERIT Award):
- Plasticity following chronic spinal injury (Golder, Fuller, Resnick)
- Potential of intermittent hypoxia to elicit functional recovery following spinal injury (Olson, Rhymer)
- Mechanisms of receptor tyrosine kinase transactivaton through Gs coupled protein receptors and potential for therapeutic application to spinal injury.
Compensation via respiratory plasticity in a rodent model of amyotrophic lateral scherosis (ALS)
- Mechanisms preserving ventilatory function despite respiratory motor neuron death.
- VEGF and BDNF induced respiratory plasticity in normal and mutant rats
.
- Motor neuron rescue with neural progenitor implants secreting growth factors (Svendsen).
Johnson, S.M. and G.S. Mitchell (2000). Activity-dependent plasticity of descending synaptic inputs to spinal respiratory motoneurons in an in vitro turtle brainstem-spinal cord preparation. J. Neurosci. 200: 3487-3495. [Abstract]
Johnson, R.A., A.J. Okragly, M. Haak-Frendscho and G.S. Mitchell (2000). Spinal sensory denervation increases BDNF and NT-3 expression in the ventral spinal cord. J. Neuroscience 20: RC77, 1-5. [Abstract]
Mitchell, G.S., K.B. Bach, P.A. Martin, K.T. Foley, E.B. Olson, Jr., M.S. Brownfield, V. Miletic, M. Behan, S.M. McGuirk and H.E. Sloan (2000). Increased spinal monoamine concentrations following chronic thoracic dorsal rhizotomy in goats. J. Appl. Physiol. 89: 1266-1274. [Abstract]
Baker, T.L.and G.S. Mitchell (2000). Episodic, but not continuous hypoxia elicits long-term facilitation of phrenic motor output. J. Physiol. (London) 529: 215-219. [Abstract]
Fuller, D., T.L. Baker, M. Behan and G.S. Mitchell (2001). Expression of hypoglossal long term facilitation differs between sub-strains of Sprague Dawley rats. Physiol. Genomics 4: 175-181. [Abstract]
Fuller, D.D., A.G. Zabka, T.L. Baker and G.S. Mitchell (2001). Phrenic long-term facilitation requires 5-HT receptor activation during but not following episodic hypoxia. J. Appl. Physiol. 90: 2001-2006 (Featured Paper). [Abstract]
Zabka, A.G., M. Behan and G.S.Mitchell (2001). Serotonin-dependent long-term facilitation of respiratory motor output decreases with age in male rats. J. Physiol. (London ) 531: 509-514.
Mitchell, G.S., T.L. Baker, S.A. Nanda, D.D. Fuller, A.G. Zabka, B.A. Hodgeman, R.W. Bavis, K.J. Mack and E.B. Olson, Jr. (2001) Intermittent hypoxia and respiratory plasticity J. Appl. Physiol. 90: 2466-2475. [Abstract]
Olson, E.B., Jr., C.J. Bohne, M.R. Dwinell, A. Podolsky, E.H. Vidruk, D.D. Fuller, F.L. Powell and G.S. Mitchell (2001). Ventilatory long-term facilitation in unanesthetized rats. J. Appl. Physiol. 91: 709-716. [Abstract]
Ling, L., D.D. Fuller, K.B. Bach, R. Kinkead, E.B. Olson, M. Behan and G.S. Mitchell (2001). Chronic intermittent hypoxia elicits serotonin-dependent plasticity in the central neural control of breathing. J. Neuroscience 21: 5381-5388.[Abstract]
Fuller, Z. Wang, D., L. Ling, E.B. Olson, G.E. Bisgard and G.S. Mitchell (2001). Induced recovery of hypoxic phrenic responses in adult rats exposed to hyperoxia for the first month of life. J. Physiol. (London) 536: 917-926. [Abstract]
Baker, T.L., D.D. Fuller, A.G. Zabka and G.S. Mitchell (2001). Respiratory plasticity: differential actions of continuous and episodic hypoxia and hypercapnia. Respiration Physiology 129: 25-35. [Abstract]
Zabka, A.G., M. Behan and G.S. Mitchell (2001). Time-dependent hypoxic respiratory responses in female rats are influenced by age and by the estrus cycle. J. Appl. Physiol. 91: 2831-2838 (Featured Paper). [Abstract]
Fuller, D.D., R.W. Bavis, E.H. Vidruk, Z.-Y. Wang, E.B. Olson, Jr., G.E. Bisgard and G.S. Mitchell (2002). Life-long impairment of hypoxic phrenic responses in rats following one month of developmental hyperoxia. J. Physiol. (London). 538: 947-955.
Bavis, R.W., E.B. Olson, Jr. and G.S. Mitchell (2002). Critical developmental period for hyperoxia-induced blunting of hypoxic phrenic responses in rats. J. Appl.Physiol. 92: 1013-1018. [Abstract]
Baker, T.L. and G.S. Mitchell (2002). Long-term facilitation of respiratory motor output requires spinal serotonin receptor activation and protein synthesis. J. Neurosci. 22: 6239-6246. [Abstract]
Bavis, R.W. and G.S. Mitchell (2003). Intermittent hypoxia induces phrenic long-term facilitation in carotid denervated rats. J. Appl. Physiol. 94: 399-409. (Featured Paper) [Abstract]
Mitchell, G.S. and S.M. Johnson (2003).Neuroplasticity in respiratory motor control . J. Appl. Physiol. 94: 358-374.[Abstract]
Fuller, D.D., S.M. Johnson, E.B. Olson and G.S. Mitchell (2003). Synaptic pathways to phrenic motoneurons are enhanced by chronic intermittant hypoxia after cervical spinal cord injury. J. Neuroscience. 23: 2993-3000. [Abstract]
Feldman, J.L., G.S. Mitchell and E.E. Nattie (2003). Breathing: rhythmicity, plasticity and chemosensitivity. Annual Review of Neuroscience. 26: 239-266. [Abstract]
Johnson, R.A., J.S. Rhodes, S.L. Jeffrey, T. Garland, Jr. and G.S. Mitchell (2003). Hippocampal brain derived neurotrophic factor but not neurotrophin-3 increases more in mice selected for increased voluntary wheel running. Neuroscience. 121: 1-7. [Abstract]
Zabka, A.G., G.S. Mitchell, E.B. Olson and M. Behan (2003). Chronic intermittent hypoxia enhances respiratory long-term facilitatioin in geriatric female rats. J. Appl. Physiol. PMID 12937027. [Abstract]
Rhodes, J.S., H. vanPragg, S. Jeffrey, I. Girard, G.S. Mitchell, T. Garland, Jr. and F.H. Gage (2003). Exercise increases hippocampal neurogenesis to high levels but does not improve spatial learning in mice bred for increased voluntary wheel running. Behavioral Neurosci. [Abstract]
Grants:
NIH R37-HL 69064
Dr. G. Mitchell (P.I.)12/2001 - 11/2011
MERIT AWARDNIH RO1 HL89209
Dr. G. Mitchell (P.I.)7/2005 - 6/2009
Mechanisms of respiratory long-term facillitation NIH 1PO1NS057778-01
Dr. G. Mitchell (P.I.project 1)
Dr. C. Svendsen (Program Director)7/2007 - 6/2012
Stem cell and growth factor therapy for ALS
Project 1 Respiratory Plasticity in the SOD1G93A rat
Collaborative Grants:
NIH RO1 AG18760
Dr. M. Behan (P.I.)
Dr. G. Mitchell (Co.I)3/2007 - 2/2012
Age, gender serotonin and respiratory control ALS Association #801B
Dr. C. Svendsen (Co.P.I.)
Dr. G. Mitchell (Co.P.I.)
2/2005 - 1/2007Combined delivery of growth factors and astrocytes as potential ALS treatment
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Updated
06/29/2007