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Our laboratory focuses on two debilitating – and possibly related – diseases: epilepsy and autism. Epilepsy is the most common disease associated with autism, so it is likely that the two disorders share common etiologies. Unfortunately, medical research has yet to produce preventatives or cures for either disease. Our research seeks to understand the basic mechanisms behind the development of these diseases. By understanding the building blocks of the diseases, we hope to develop new and more effective treatments for them.
Diseases affecting the developing brain are some of the most devastating, and difficult to treat, pediatric ailments. Many of these diseases are hard to diagnose, lack effective treatments and become more severe with time. Making matters worse, developing neurons are extremely vulnerable cells. Their growth can be disrupted directly by the disease, secondarily as normal brain regions suffer from abnormal activity in the affected brain region, and even as an unwanted side effect from medications for symptoms such as seizures.
One brain region that is particularly vulnerable is the hippocampal dentate gyrus. These neurons are among the last to be generated in the brain, and are one of the few populations of neurons produced in the adult brain. Our research focuses on the effects of epilepsy and autism on this brain region, and investigates the role aberrant cells in this region may play in the development of epilepsy.
Pun RYK, Rolle IJ, LaSarge CL, Hosford BE, Rosen JM, Uhl JD,
Schmeltzer SN, Faulkner C, Bronson SL, Murphy BL, Richards DA, Holland KD and
SC Danzer. Excessive Activation of mTOR in Postnatally Generated Granule Cells Is Sufficient to Cause Epilepsy. Neuron. 2012 Sep 20;75(6):1022-34.
Castro OW, Santos VR, Pun RYK, McKlveen JM, Batie M, Holland
KD, Gardner M, Garcia-Cairasco N, Herman JP and SC Danzer. Impact of corticosterone treatment on spontaneous seizure frequency and epileptiform activity in mice with chronic epilepsy. PLoS One. 2012;7(9):e46044.
BL, Hofacer RD, Faulkner CN, Loepke AW and SC Danzer. Abnormalities of granule cell dendritic structure are a prominent feature of the intrahippocampal kainic acid model of epilepsy despite reduced post-injury neurogenesis. Epilepsia. 2012 May;53(5):908-21.
Danzer SC. Depression, stress, epilepsy and adult neurogenesis. Experimental Neurology. 2012 Jan;233(1):22-32.
Santos VR, Wagner de Castro O, Pun RYK, Hester MS, Murphy
BL, Loepke AW, Garcia-Cairasco N and SC Danzer. Contributions of mature granule cells to structural plasticity in temporal lobe epilepsy. Neuroscience. 2011 Dec 1;197:348-57.
Murphy BL and SC Danzer. Somatic translocation: a novel mechanism of granule cell dendritic dysmorphogenesis and dispersion. Journal of Neuroscience. 2011 Feb 23;31(8):2959-64.
Tokuda S, Mahaffey CL, Monks B, Faulkner CR, Birnbaum MJ,
Danzer SC and WN Frankel. A novel Akt3 mutation associated with enhanced kinase activity and seizure susceptibility in mice. Human Molecular
Genetics. 2011 Mar 1;20(5):988-99.
Istaphanous GK, Howard J, Nan X, Hughes HA, McCann JC,
McAuliffe JJ, Danzer SC and AW Loepke. Comparison of the Neuroapoptotic Properties of Equipotent Anesthetic Concentrations of Desflurane, Isoflurane,or Sevoflurane in Neonatal Mice. Anesthesiology. 2011 Mar;114(3):578-87.
Murphy BL, Pun RY, Yin H, Faulkner CR, Loepke AW and SC
Danzer. Heterogeneous integration of adult-generated granule cells into the epileptic brain. Journal of Neuroscience. 2011 Jan 5;31(1):105-17.
JJ, Bronson SL, Hester MS, Murphy BL, Dahlquist-Topalá R, Richards DA and SC
Danzer. Altered patterning of dentate granule cell mossy fiber inputs onto CA3 pyramidal cells in limbic epilepsy. Hippocampus. 2011 Jan;21(1):93-107.
McDole J, Danzer SC, Pun RYK, Chen Y, Johnson HL, Pirko I, Johnson AJ. Rapid formation of extended processes and engagement of Theiler’s virus-infected neurons by CNS-infiltrating CD8 T cells. American Journal of Pathology. 2010 Oct;177(4):1823-33.
Danzer SC, He XP, Loepke AW, McNamara JO. Structural plasticity of dentate granule cell mossy fibers during the development of limbic epilepsy. Hippocampus. 2010 Jan;20(1):113-24.
Danzer SC. Postnatal and adult neurogenesis in the development of human disease. Neuroscientist. 2008 Oct;14(5):446-58.
Walter C, Murphy BL, Pun RYK, Spieles-Engemann AL and SC
Danzer. Pilocarpine-induced seizures cause selective time-dependent changes to adult-generated hippocampal dentate granule cells. Journal of
Neuroscience. 2007 Jul 11;27(28):7541-52.
Danzer SC and McNamara JO. Localization of BDNF to distinct terminals of mossy fiber axons implies regulation of both excitation and feedforward inhibition of CA3 pyramidal cells. Journal of
Neuroscience. 2004 Dec 15;24(50):11346-55.
Danzer SC, Crooks KRC, Lo DC and McNamara JO. Increased basal dendrites and axonal branching of BDNF-transfected dentate granule cells in hippocampal explant cultures. Journal of Neuroscience. 2002 Nov 15;22(22):9754-63.
Read more about how the Danzer lab’s research into neuron development in the brain’s hippocampus region may lead to safer treatment options for children and adults with epilepsy.
Steve Danzer, PhDAssociate Professor
Division of Anesthesia3333 Burnet Ave. MLC 2001 Cincinnati, OH 45229
Office Phone: 513-636-4526 Lab Phone: 513-636-6235 Fax: 513-636-7337 Email: email@example.com
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