Margarita C. Currįs-Collazo
Associate Professor of Cell Biology & Neuroscience
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Biomedical Research Signal Transduction B.S., 1982, Biology and Psychology with Honors,
Tulane University VOICE: 951-827-3960 |
Research in our laboratory concerns neuroendocrinology, neural control of hydromineral balance and effect of endocrine disruptors, dendritic signalling and autoregulation of neuronal circuits as well as mechanisms underlying excitotoxicity and neuroprotection. One main focus of our research is autocontrol of neuroendocrine cells of the supraoptic nucleus of the rat hypothalamus (SON) which produce vasopressin (VP) and oxytocin (OXY), hormones involved in osmoregulation, lactation and parturition as well as cardiovascular function. We are investigating the physiological significance of dendritic signalling by VP and the mechanisms underlying this phenomenon including the actions of nitric oxide, PACAP and glutamate receptors. A recent finding, modulation of stimulated glutamate release by VP and OXY, suggests that locally released OXT and VP may autoregulate SON activity, in part, by modulating the release of excitatory amino acids from afferent terminals targeting these cells. Studies are underway that examine the receptor subtypes and signal transduction processes involved in VP's presynaptic effects and the possible disruption of neuroendocrine autocontrol by the environmental toxins, persistent organic pollutants. A recent finding, modulation by VP and OXY of stimulated glutamate release, suggests that locally released OXT and VP may autoregulate SON activity, in part, by modulating the release of excitatory amino acids from afferent terminals targeting these cells. Studies are underway that examine the receptor subtypes and signal transduction processes involved in VP's presynaptic effects and the possible disruption of neuroendocrine autocontrol by the environmental toxins, polychlorinated biphenyls. NMDA-type GLU receptors also mediate excitotoxicity associated with neurodegeneration and stroke-induced neuronal death. Interestingly, we have demonstrated that neuroendocrine cells of the SON are less susceptible to excitotoxic injury (in vitro) and ischemic neuronal death (in vivo) relative to cortical and other central neurons. Current projects in my laboratory aim to identify important neuroprotective mechanisms relevant to SON viability. Our lab has recently discovered that resistance to glutamate-evoked excitotoxicity may be associated with a greater capacity for glutamate clearance and more efficient calciium extrusion and free radical scavenging. A recent interest in the role of calcium in histopathology resulting from traumatic brain injury has led to an ongoing MRI study using a rat model. Our findings may lead eventually to the development of alternative therapies for stroke and neurodegenerative diseases. Other projects focus on the secondary mechanisms leading to toxicity caused by domoic acid poisoning. Methods employed in our laboratory include patch-clamp electrophysiology (see Figure 1), Western blot analysis (Fig. 2), immunohistochemistry, radioligand uptake, in vitro bioassays including enzyme immunoassay measurement of VP release, tissue culture, antisense methods and whole animal physiology.
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Figure 1. Single-channel currents indicative of NR2B-containing NMDA receptors on cultured neuroendocrine cells. Single channel activity was recorded from an outside-out patch pulled from a cultured neuroendocrine cell obtained from embryonic supraoptic nucleus of the hypothalamus (SON) and held at ?0 mV. TOP TRACES: Pulse applications of 300 uM NMDA and 10 uM glycine evoked inward currents having a maximum unitary conductance of ~50 pS. MIDDLE TRACES: Test solution applied in the continuous presence of 10 uM ifenprodil, an NR2B-selective antagonist, abolished the maximum conductance events and uncovered lower conductance channel openings (~37 pS). BOTTOM TRACES: Maximum conductance openings are recovered after washout of ifenprodil. |
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Figure 2. Dynamic expression of NR2B in the SON is dependent on osmotic state. Homogenates of SON (20 ug) and COR (5 ug) obtained from control and saline-treated rats were loaded in individual lanes of a 6% acrylamide gel and subjected to SDS-PAGE. Immunoblots were probed with an anti-rat NR2B antibody. Saline water drinking for 7 days produces a decrease in NR2B immunoreactivity at ~180 kDa in the supraoptic nucleus of the hypothalamus (SON) but not in the frontal cortex (COR) of the same rat. NR2B levels are back to normal in SON after 6 days of rehydration (Recovery). |
SELECTED PUBLICATIONS:
Currįs, M. C. and B. S. Pallotta. 1996. Single-channel evidence for glycine and NMDA requirement in NMDA receptor activation. Brain Res. 740:27-40.
Decavel, C. and M. C. Currįs. 1997. Increased expression of the NMDA receptor subunit, NR1, in immunohistochemically identified magnocellular hypothalamic neurons during dehydration. Neuroscience 78(1):191-202.
Currįs, M. C., P. Rack and R. B. Meeker. 1998. Channel properties of NMDA glutamate receptors on magnocellular neuroendocrine cells cultured from the rat supraoptic nucleus. Brain Res. 789:181-193 (cover article).
Khan, A.M., M. C. Currįs, J. Dao, F. A. Jamal, C. A. Turkowski, R. K. Goel, E. Gillard, S. D. Wolfsohn and B. G. Stanley. 1999. Lateral hypothalamic NMDA receptor subunits NR2A and/or NR2B mediate eating: immuno-chemical/behavioral evidence. Am. J. Physiol. 276 (Regulatory Integrative Comp. Physiol. 45): R880-R891.
Meeker, R.B., M.C. Currįs, J. Stewart, A. Serje, and W. Al-Ghoul. 1999. Functional activation of punch-cultured magnocellular neuroendocrine cells by glutamate receptor subtypes. J. Neurosci. Meth. 89:57-67.
Currįs-Collazo, M. C. and J. Dao. 1999. Osmotic activation of the hypothalamo-neurohypophysial system reversibly downregulates the NMDA receptor subunit, NR2B, in the supraoptic nucleus of the hypothalamus. Mol. Brain Res. 70(2):187-196.
Margarita C. Pak, C.W. and M.C. Currįs-Collazo. 2002. Expression and Plasticity of Glutamate Receptors in the Supraoptic Nucleus of the Hypothalamus. Microscopy Research and Technique 56:92-100.
Currįs-Collazo, M.C., Patel, U.B. and M.O. Hussein. 2002. Reduced susceptibility of rat magnocellular neuroendocrine nuclei to transient focal ischemia produced by middle cerebral artery occlusion. Experimental Neurology (in press)
Currįs-Collazo, M.C., Gillard, E.R., Jin, J. and J. Pandika. Vasopressin and oxytocin decrease excitatory amino acid release in adult rat supraoptic nucleus. J. Neuroendocrinology (in press)
Pak, C.W. and M.C. Currįs-Collazo. Expression and Plasticity of Glutamate Receptors in the Supraoptic Nucleus of the Hypothalamus. Microscopy Research and Technique 56:92-100, 2002
Currįs-Collazo, M. C., U. Patel and M. O. Hussein. Reduced susceptibility of rat magnocellular neuroendocrine nuclei to transient focal ischemia produced by middle cerebral artery occlusion. Experimental Neurology 178(2):268-279, 2002.
M.C. Currįs-Collazo, E.R. Gillard, J. Jin, and J. Pandika. Vasopressin and oxytocin decrease excitatory amino acid release in adult rat supraoptic nucleus. J. Neuroendocrinol. 15(2):182-90, 2003.
Coburn, C.G., Gillard, E.R. and M.C. Curras-Collazo. Dietary exposure to Aroclor 1254 alters central and peripheral vasopressin release in response to dehydration in the rat. Toxicological Sciences 84(1):149-56, 2005.
CURRĮS-COLLAZO LABORATORY GROUP
