Find A PhysicianHome  |  Library  |  myDownstate  |  Newsroom  |  A-Z Guide  |  E-mail  |  Contact Us  |  Directions
curve gif
Photo of H. Moreno

Herman Moreno

Assistant Professor of Neurology
Assistant Professor of Physiology and Pharmacology
M.D. (1988, University of Caldas)

Tel: 718 270-4660 • e-mail: herman.moreno@downstate.edu


Brain metabolism and calcium dynamics in neurodegeneration

Our laboratory is interested in normal brain function during the ageing process, as well as the study of neurodegenerative diseases. We study multiple genetically modified mice that resemble human neurodegenerative disease, mainly AD, Down syndrome and Huntington disease mice models and mice that express abnormal levels of calcium binding proteins, and combinations of these.

The methods are a combination of functional and structural micro MRI (in vivo mice imaging) with in vitro neuronal-(axon and dendrites) calcium imaging and basic electrophysiology of the hippocampus.

Our main hypothesis is that cognitive deficits in ageing and some neurobehavioral entities are related to altered central nervous system calcium homeostasis, in specific subregions of the hippocampal formation. Since the MRI-techniques (Steady-State Cerebral Blood Volumes) that we have developed in mice can be safely applied to humans, we have started a series of collaboration imaging humans with a variety of neurocognitive deficits.

 

MRI-related
Almost all in-vivo techniques that measure brain metabolism are based on Fickís principle. This principle describes a relationship between oxidative metabolism and hemodynamic variables ó cerebral blood flow (CBF), cerebral blood volume (CBV) and deoxyhemoglobin (dHb) ó to assess metabolism in the living brain. These techniques include: Near infrared spectroscopy, contrast enhanced computerized tomography to evaluate cerebral blood volume (CBV), PET and single-photon emission tomography measurements of cerebral blood flow (CBF), and magnetic resonance imaging (MRI) measurements of CBF, CBV, and deoxyhemoglobin.
We have focused our attention on MRI-CBV because it can visualize small structures such as the hippocampal subregions with better resolution
n than other techniques such as PET. The basic idea is that a change in MRI signal caused by a shift in the intravascular concentration of a contrast agent is proportional to local blood volume. All data is presented as normalized ΔR2 values=rCBV, relative CBV. ΔR2 is the change in relaxation rate (1/T2), mainly in the microvasculature, induced by a contrast agent. All MRI experiments are performed with a Brucker AVANCE 400WB spectrometer, outfitted with an 89 mm bore 9.4 tesla vertical Brucker magnet.

Electrophysiology-related
Using MRI-CBV we identified the hippocampal areas that show abnormal metabolism at the earliest time point in AD and DS mouse models. Then, we performed two types of electrophysiological measurements: a) hippocampus (subiculum and CA3 pyramidal neurons) field and intracellular recordings to interrogate the circuit properties of these areas and their synaptic plasticity in J20 and Ts65Dn mice. This set-up is optimal to study animals of any age. b) patch-clamp, coupled with a high performance EM-CCD camera to study basic electrophysiological properties of individual subicular pyramidal neurons and their calcium signals in three compartments: soma, dendrites and axons. Since fMRI data are indirect measurements, we proposed to confirm imaging findings with independent measures of neuronal dysfunction, such as electrophysiology and calcium signaling.


Figure 1. Calcium transient at a dentate gyrus granule cell mossy fiber bouton. Shown are DG cells labeled with OG-1AM, before and after a 50 Hz train of 8 action potentials.

Figure 2. Mouse hippocampal subregional CBV maps. Axial T2 weighted image at the level of the midbody of the hippocampus. Shown are: entorhinal cortex, red; subiculum, blue; CA1, green; CA3, yellow; dentate gyrus, light blue.

 

Selected Publications

Lev, S., Moreno, H., Martinez, R., Canoll, P., Peles, E., Mussachio, M., Plowman, G., Rudy, B., and Schlessinger, J. (1995). Protein tyrosine kinase PYK2 involved in Ca2+ induce regulation of ion channel and MAP kinase functions. Nature 376, 737-745

Moreno, H., Sugimori, M., Lesnik, E., Lax, I., Schlessinger, J., and Llinás, R. (1998). Nerve growth factor acutely inhibits chemical transmission by means of postsynaptic TrkA like receptors in squid giant synapse. Proc. Natl. Acad. Sci. USA 95, 14997-15002

Llinas, R., and Moreno, H. (1998). Local Ca2+ signaling in neurons. Harcourt Brace and Co. Edited by O. Petersen and A. Verkhratsky. Cell Calcium 24(5-6), 359-66.

Moreno Davila, H. (1999). Molecular and functional properties of voltage gated calcium channels in the CNS. Annals of the New York Academy of Sciences 868, 102-118

Caillard, O., Moreno, H., Schwaller, B., Llano, I., Celio, M., and Marty, A. (2000). Role of the calcium-binding protein parvalbumin in short-term synaptic plasticity. Proc. Natl. Acad. Sci. USA 97, 13372-13377.

Moreno, H., Vega-Saenz de Miera, E., Nadal, M., Amarillo, Y., and Rudy, B. (2001). Modulation of Kv3 potassium channels expressed in CHO cells by a nitric oxide-activated phosphatase. J Physiol. 530, 345-58

Collin,T., Chat, G., Moreno, H., Marty, A., and Llano, I. (2005). Developmental changes in Parvalbumin regulate presynaptic calcium signals. J. Neurosci. 25, 96-107

Moreno,H., Hua, F., Brown, T., and Small, S. (2006). Longitudinal mapping of mouse cerebral blood volume with MRI. NMR in Biomed.19, 535-543.

Moreno, H., Wu, W., Lee, T., Wu, W., Mayeux, R., Brown, T., and Small, S. (2007). Imaging the Aβ-related neurotoxicity of Alzheimer disease. Arch Neurol. 64, 1467-77.

List of Publications (Pub Med)


Personnel

Sergio Angulo, M.D., Postdoctoral Fellow
Daniel Vela, M.D., Postdoctoral Fellow


Service Functions

Reviewer, Alzheimer Association Grants
Permanent Faculty Latin-American IBRO course on Cellular and Molecular Neurobiology

E-mail: herman.moreno@downstate.edu

Return to Department of Physiology and Pharmacology Home Page

Return to SUNY Brooklyn Home Page