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Current Opinion in Neurobiology 2005 Calendar
A confocal image showing a CA3 pyramidal cell apical dendrite decorated with thorny excrescences (blue) intersecting with dentate granule cell mossy fiber axons (red) and a granule cell giant mossy fiber bouton (red and green) in stratum lucidum of the hippocampus. Images are of green fluorescent protein (GFP) expressing neurons. The long axis of the image is 45 microns.
Danzer SC, He XP, McNamara JO. Ontogeny of Seizure-Induced Increases in BDNF Immunoreactivity and TrkB Receptor Activation in Rat Hippocampus. Hippocampus. 14: 345-355. 2004.
Transmission confocal microscopy image of BDNF immunohistochemistry (red) and phospho-Trk immunohistochemistry (green) in the hippocampus of a 22-day-old rat 24 hours after kainate-induced status epilepticus. Images of BDNF and phospho-Trk immunohistochemistry were taken from adjacent sections from the same animal and superimposed. Colocalization of BDNF and phospho-Trk immunoreactivity is shown in the mossy fiber pathway.
Danzer SC, Crooks KRC, Lo DC, McNamara JO. Increased expression of brain-derived neurotrophic factor induces formation of basal dendrites and axonal branching of BDNF-transfected dentate granule cells in hippocampal explant cultures. Journal of Neuroscience. 22: 9754-9763. 2002.
Composite image showing dentate granule cells biolistically transfected with green fluorescent protein (GFP)or GFP plus brain-derived neurotrophic factor (BDNF). Immunoreactivity for hemagglutinin-tagged BDNF is illustrated in red. Endogenous autofluorescence of the granule cell layer is shown in blue. Basal dendrites are shown in green. Plasmid-coated gold particles (1.6 µm) are shown in white. BDNF-transfected granule cells exhibit both axonal and dendritic sprouting.
Danzer SC, Pan E, Nef S, Parada LF, McNamara JO. Altered regulation of brain-derived neurotrophic factor protein in hippocampus following slice preparation. Neuroscience. 126(4):859-69. 2004.
Confocal image of BDNF immunostaining (red) in CA3b of the hippocampus of a control-treated mouse which expresses GFP in a subset of hippocampal neurons under control of the Thy1 promoter (mice kindly provided by Guoping Feng, Duke University). The upper and lower bands of BDNF immunostaining correspond to the mossy fiber projection in stratum lucidum, and the infrapyramidal mossy fiber projection, respectively. GFP expressing mossy fibers and CA3 pyramidal neurons are shown in blue. BDNF immunoreactive giant mossy fiber boutons appear green.
Society for Neuroscience Annual Meeting Brochure
Confocal image showing a dentate granule cell in an organotypic hippocampal slice culture. This granule cell has been transfected with brain-derived neurotrophic factor and green fluorescent protein. It exhibits increased dendritic and axonal branching relative to granule cells transfected with green fluorescent protein alone.
Danzer SC, Kotloski RJ, Walter C, Hughes M, McNamara JO. Altered morphology of hippocampal dentate granule cell presynaptic and postsynaptic terminals following conditional deletion of TrkB. Hippocampus. 18(7):668-78. 2008.
Montage of confocal maximum projections showing hippocampal dentate granule cell bodies and proximal dendrites from TrkB null (left column) and TrkB wild type (right column) mice. Granule cells from TrkB null animals possessed significantly fewer primary dendrites – defined as dendritic processes originating from the cell body – relative to granule cells from animals with normal levels of TrkB. Granule cells were labeled with green fluorescent protein by crossing TrkB mutant mice to Thy1-GFP expressing mice. For all six cells, apical dendrites are oriented towards the top and axons towards the bottom of the figure.
Danzer SC. Postnatal and adult neurogenesis in the development of human disease. The Neuroscientist. 14:446-458. 2008.
In the normal brain, hippocampal dentate granule cells are born along the border between the dentate granule cell layer (DGC-L) and the hilus. After birth, these new cells migrate the short distance to take up residence in the granule cell layer. In stark contrast, in response to epileptogenic brain injury newborn cells migrate the wrong direction and come to reside in the dentate hilus (arrows). These ectopic cells project their dendrites in erratic directions, and are postulated to contribute to epileptogenesis.
Stress in the development and progression of epilepsy
Stress is widely recognized as a factor for provoking seizures in many patients with epilepsy. But despite clear evidence for a link between stress and seizures in humans, exactly how stress affects the occurrence of seizures in patients with epilepsy is not well understood. A better understanding of this process could lead to new strategies to control seizures. The goal of this project, therefore, is to explore the relationship between stress, stress hormones and seizures in animal models of epilepsy.
2008-2010 − Charles L. Shor Foundation for Epilepsy Research. Cincinnati.SC Danzer, coprincipal investigator (in collaboration with James Herman, UC Department of Psychiatry).
Short- and long-term impact of neonatal seizures on hippocampal granule cell integration
Seizures in children are common. The long-term consequences of these seizures, however, are still unclear. We examine the effect of neonatal seizures on the development of a brain region critical for learning, language development, cognition and imagination. These studies will help us determine how neonatal seizures may harm young brains and will guide the development of treatments to mitigate that damage.
2009-2011 − National Institutes of Health, 1R03-NS-064378-01.SC Danzer, principal investigator
Selective disruption of hippocampal dentate granule cells in autism: impact of PTEN deletion
This research intends to determine whether selective disruption of late-generated neurons – specifically hippocampal dentate granule cells – contributes to the development of autism. Although the proximal cause of autism is undetermined in most cases, the late generation of these neurons (in the late embryonic period and in infancy) may make them uniquely vulnerable to a variety of insults faced by the newborn child (e.g., infection). A connection between seizure-generated disruption in these cells and the development of autism could offer a path to mitigate or prevent autism. We will examine the role these neurons play by selectively eliminating genes implicated in autism in these cells in transgenic mice.
2009-2014 − National Institutes of Health, 1R01-NS-065020-01. SC Danzer, principal investigator.
Contributions of aberrant granule cell integration to the development of epilepsy
In adults, new brain cells are born daily in the hippocampus, a region that plays a role in common forms of epilepsy. Abnormal incorporation of these new cells into the brain may promote the development of the disease. We will investigate the role these new neurons play in the pathology, development and maintenance of epilepsy. By determining how normal brains become epileptic, we can begin to develop therapies to delay, halt and ultimately reverse the process.
2009-2014 − National Institutes of Health, 1R01-NS-062806. SC Danzer, principal investigator.
Steve Danzer, PhDAssociate Professor
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