Faculty Bibliography
Searched for:
Department/Unit:Neuroscience Institute
Total Results:
13562
Synaptic vesicle exocytosis in hippocampal synaptosomes correlates directly with total mitochondrial volume
Synaptic plasticity in many regions of the central nervous system leads to the continuous adjustment of synaptic strength, which is essential for learning and memory. In this study, we show by visualizing synaptic vesicle release in mouse hippocampal synaptosomes that presynaptic mitochondria and, specifically, their capacities for ATP production are essential determinants of synaptic vesicle exocytosis and its magnitude. Total internal reflection microscopy of FM1-43 loaded hippocampal synaptosomes showed that inhibition of mitochondrial oxidative phosphorylation reduces evoked synaptic release. This reduction was accompanied by a substantial drop in synaptosomal ATP levels. However, cytosolic calcium influx was not affected. Structural characterization of stimulated hippocampal synaptosomes revealed that higher total presynaptic mitochondrial volumes were consistently associated with higher levels of exocytosis. Thus, synaptic vesicle release is linked to the presynaptic ability to regenerate ATP, which itself is a utility of mitochondrial density and activity.
PMCID:3488359
PMID: 22772899
ISSN: 0895-8696
CID: 210992
Monitoring axonal and somatodendritic dopamine release using fast-scan cyclic voltammetry in brain slices
Brain dopamine pathways serve wide-ranging functions including the control of movement, reward, cognition, learning, and mood. Consequently, dysfunction of dopamine transmission has been implicated in clinical conditions such as Parkinson's disease, schizophrenia, addiction, and depression. Establishing factors that regulate dopamine release can provide novel insights into dopaminergic communication under normal conditions, as well as in animal models of disease in the brain. Here we describe methods for the study of somatodendritic and axonal dopamine release in brain slice preparations. Topics covered include preparation and calibration of carbon-fiber microelectrodes for use with fast-scan cyclic voltammetry, preparation of midbrain and forebrain slices, and procedures of eliciting and recording electrically evoked dopamine release from in vitro brain slices.
PMID: 23296788
ISSN: 1064-3745
CID: 211502
Surgical Decompression is Associated with Decreased Mortality in Patients with Sepsis and Ureteral Calculi
PURPOSE: The combination of sepsis and ureteral calculus is a urological emergency. Traditional teaching advocates urgent decompression with nephrostomy tube or ureteral stent placement, although published outcomes validating this treatment are lacking. National practice patterns for such scenarios are currently undefined. Using a retrospective study design, we defined the surgical decompression rate in patients admitted to the hospital with severe infection and ureteral calculi. We determined whether a mortality benefit is associated with this intervention. MATERIALS AND METHODS: Patient demographics and hospital characteristics were extracted from the 2007 to 2009 Nationwide Inpatient Sample. We identified 1,712 patients with ureteral calculi and sepsis. Multivariate logistic regression was performed to determine the association between mortality and surgical decompression. RESULTS: Of the patients 78% underwent surgical decompression. Mortality was higher in those not treated with surgical decompression (19.2% vs 8.82%, p <0.001). Lack of surgical decompression was independently associated with an increased OR of mortality even when adjusting for patient demographics, comorbidities and geographic region of treatment (OR 2.6, 95% CI 1.9-3.7). CONCLUSIONS: Absent surgical decompression is associated with higher odds of mortality in patients with sepsis and ureteral calculi. Further research to determine predictors of surgical decompression is necessary to ensure that all patients have access to this life saving therapy.
PMID: 23017519
ISSN: 0022-5347
CID: 210832
BDNF-estrogen interactions in hippocampal mossy fiber pathway: implications for normal brain function and disease
The neurotrophin BDNF and the steroid hormone estrogen exhibit potent effects on hippocampal neurons during development and in adulthood. BDNF and estrogen have also been implicated in the etiology of diverse types of neurological disorders or psychiatric illnesses, or have been discussed as potentially important in treatment. Although both are typically studied independently, it has been suggested that BDNF mediates several of the effects of estrogen in hippocampus, and that these interactions play a role in the normal brain as well as disease. Here we focus on the mossy fiber (MF) pathway of the hippocampus, a critical pathway in normal hippocampal function, and a prime example of a location where numerous studies support an interaction between BDNF and estrogen in the rodent brain. We first review the temporal and spatially-regulated expression of BDNF and estrogen in the MFs, as well as their receptors. Then we consider the results of studies that suggest that 17beta-estradiol alters hippocampal function by its influence on BDNF expression in the MF pathway. We also address the hypothesis that estrogen influences hippocampus by mechanisms related not only to the mature form of BDNF, acting at trkB receptors, but also by regulating the precursor, proBDNF, acting at p75NTR. We suggest that the interactions between BDNF and 17beta-estradiol in the MFs are potentially important in the normal function of the hippocampus, and have implications for sex differences in functions that depend on the MFs and in diseases where MF plasticity has been suggested to play an important role, Alzheimer's disease, epilepsy and addiction.
PMCID:3628287
PMID: 23276673
ISSN: 0306-4522
CID: 210432
Introduction to 'steroid hormone actions in the CNS: The role of brain-derived neurotrophic factor (BDNF)'
PMCID:4096957
PMID: 23164677
ISSN: 0306-4522
CID: 210482
Toward reliable characterization of functional homogeneity in the human brain: Preprocessing, scan duration, imaging resolution and computational space
While researchers have extensively characterized functional connectivity between brain regions, the characterization of functional homogeneity within a region of the brain connectome is in early stages of development. Several functional homogeneity measures were proposed previously, among which regional homogeneity (ReHo) was most widely used as a measure to characterize functional homogeneity of resting state fMRI (R-fMRI) signals within a small region (Zang et al., 2004). Despite a burgeoning literature on ReHo in the field of neuroimaging brain disorders, its test-retest (TRT) reliability remains unestablished. Using two sets of public R-fMRI TRT data, we systematically evaluated the ReHo's TRT reliability and further investigated the various factors influencing its reliability and found: 1) nuisance (head motion, white matter, and cerebrospinal fluid) correction of R-fMRI time series can significantly improve the TRT reliability of ReHo while additional removal of global brain signal reduces its reliability, 2) spatial smoothing of R-fMRI time series artificially enhances ReHo intensity and influences its reliability, 3) surface-based R-fMRI computation largely improves the TRT reliability of ReHo, 4) a scan duration of 5min can achieve reliable estimates of ReHo, and 5) fast sampling rates of R-fMRI dramatically increase the reliability of ReHo. Inspired by these findings and seeking a highly reliable approach to exploratory analysis of the human functional connectome, we established an R-fMRI pipeline to conduct ReHo computations in both 3-dimensions (volume) and 2-dimensions (surface).
PMCID:3609711
PMID: 23085497
ISSN: 1053-8119
CID: 210132
The 4.1B cytoskeletal protein regulates the domain organization and sheath thickness of myelinated axons
Myelinated axons are organized into specialized domains critical to their function in saltatory conduction, i.e., nodes, paranodes, juxtaparanodes, and internodes. Here, we describe the distribution and role of the 4.1B protein in this organization. 4.1B is expressed by neurons, and at lower levels by Schwann cells, which also robustly express 4.1G. Immunofluorescence and immuno-EM demonstrates 4.1B is expressed subjacent to the axon membrane in all domains except the nodes. Mice deficient in 4.1B have preserved paranodes, based on marker staining and EM in contrast to the juxtaparanodes, which are substantially affected in both the PNS and CNS. The juxtaparanodal defect is evident in developing and adult nerves and is neuron-autonomous based on myelinating cocultures in which wt Schwann cells were grown with 4.1B-deficient neurons. Despite the juxtaparanodal defect, nerve conduction velocity is unaffected. Preservation of paranodal markers in 4.1B deficient mice is associated with, but not dependent on an increase of 4.1R at the axonal paranodes. Loss of 4.1B in the axon is also associated with reduced levels of the internodal proteins, Necl-1 and Necl-2, and of alpha-2 spectrin. Mutant nerves are modestly hypermyelinated and have increased numbers of Schmidt-Lanterman incisures, increased expression of 4.1G, and express a residual, truncated isoform of 4.1B. These results demonstrate that 4.1B is a key cytoskeletal scaffold for axonal adhesion molecules expressed in the juxtaparanodal and internodal domains that unexpectedly regulates myelin sheath thickness. (c) 2012 Wiley Periodicals, Inc.
PMCID:3527682
PMID: 23109359
ISSN: 0894-1491
CID: 209572
Pharmacologic treatment of kidney stone disease
This article reviews the data on pharmacologic treatment of kidney stone disease, with a focus on prophylaxis against stone recurrence. One of the most effective and important therapies for stone prevention, an increase in urine volume, is not discussed because this is a dietary and not a pharmacologic intervention. Also reviewed are medical expulsive therapy used to improve the spontaneous passage of ureteral stones and pharmacologic treatment of symptoms associated with ureteral stents. The goal is to review the literature with a focus on the highest level of evidence (ie, randomized controlled trials).
PMID: 23177632
ISSN: 0094-0143
CID: 209012
Serial proton MR spectroscopy of gray and white matter in relapsing-remitting MS
OBJECTIVE: To characterize and follow the diffuse gray and white matter (GM/WM) metabolic abnormalities in early relapsing-remitting multiple sclerosis using proton magnetic resonance spectroscopic imaging ((1)H-MRSI). METHODS: Eighteen recently diagnosed, mildly disabled patients (mean baseline time from diagnosis 32 months, mean Expanded Disability Status Scale [EDSS] score 1.3), all on immunomodulatory medication, were scanned semiannually for 3 years with T1-weighted and T2-weighted MRI and 3D (1)H-MRSI at 3 T. Ten sex- and age-matched controls were followed annually. Global absolute concentrations of N-acetylaspartate (NAA), choline (Cho), creatine (Cr), and myo-inositol (mI) were obtained for all GM and WM in the 360 cm(3) (1)H-MRSI volume of interest. RESULTS: Patients' average WM Cr, Cho, and mI concentrations (over all time points), 5.3 +/- 0.4, 1.6 +/- 0.1, and 5.1 +/- 0.7 mM, were 8%, 12%, and 11% higher than controls' (p
PMCID:3589203
PMID: 23175732
ISSN: 0028-3878
CID: 207352
Free-breathing contrast-enhanced multiphase MRI of the liver using a combination of compressed sensing, parallel imaging, and golden-angle radial sampling
OBJECTIVE: The objectives of this study were to develop a new method for free-breathing contrast-enhanced multiphase liver magnetic resonance imaging (MRI) using a combination of compressed sensing, parallel imaging, and radial k-space sampling and to demonstrate the feasibility of this method by performing image quality comparison with breath-hold cartesian T1-weighted (conventional) postcontrast acquisitions in healthy participants. MATERIALS AND METHODS: This Health Insurance Portability and Accountability Act-compliant prospective study received approval from the institutional review board. Eight participants underwent 3 separate contrast-enhanced fat-saturated T1-weighted gradient-echo MRI examinations with matching imaging parameters: conventional breath-hold examination with cartesian k-space sampling volumetric interpolate breath hold examination (BH-VIBE) and free-breathing acquisitions with interleaved angle-bisection and continuous golden-angle radial sampling schemes. Interleaved angle-bisection and golden-angle data from each 100 consecutive spokes were reconstructed using a combination of compressed sensing and parallel imaging (interleaved-angle radial sparse parallel [IARASP] and golden-angle radial sparse parallel [GRASP]) to generate multiple postcontrast phases.Arterial- and venous-phase BH-VIBE, IARASP, and GRASP reconstructions were evaluated by 2 radiologists in a blinded fashion. The readers independently assessed quality of enhancement (QE), overall image quality (IQ), and other parameters of image quality on a 5-point scale, with the highest score indicating the most desirable examination. Mixed model analysis of variance was used to compare each measure of image quality. RESULTS: Images of BH-VIBE and GRASP had significantly higher QE and IQ values compared with IARASP for both phases (P < 0.05). The differences in QE between BH-VIBE and GRASP for the arterial and venous phases were not significant (P > 0.05). Although GRASP had lower IQ score compared with BH-VIBE for the arterial (3.9 vs 4.8; P < 0.0001) and venous (4.2 vs 4.8; P = 0.005) phases, GRASP received IQ scores of 3 or more in all participants, which was consistent with acceptable or better diagnostic image quality. CONCLUSION: Contrast-enhanced multiphase liver MRI of diagnostic quality can be performed during free breathing using a combination of compressed sensing, parallel imaging, and golden-angle radial sampling.
PMCID:3833720
PMID: 23192165
ISSN: 0020-9996
CID: 202342
