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NMDA Receptor Function in Lead Neurotoxicity

Award Number: R01ES006189
ORGANIZATION: NATIONAL INSTITUTE OF ENVIRONMENTAL HEALTH SCIENCES
OPDIV: NIH
AWARD CLASS: DISCRETIONARY
AWARD ACTIVITY TYPE: SCIENTIFIC/HEALTH RESEARCH (INCLUDES SURVEYS)
PERIOD OF PERFORMANCE START DATE: 12/01/1992
PERIOD OF PERFORMANCE END DATE: 06/30/2021

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NMDA Receptor Function in Lead Neurotoxicity - ¿ DESCRIPTION (provided by applicant): Epidemiological studies during the last decade have described an association between chronic early life lead (Pb2+) exposure (CELLE) and mental disorders later in life, for example schizophrenia (SZ). There is scientific evidence that some of these mental health problems are the result of alterations in the function of the N- methyl-D-aspartate receptors (NMDAR) complex. The NMDAR is important for brain development, synaptic plasticity, learning and memory; and, Pb2+ is a potent inhibitor of the NMDAR. During the last 20 years, the long-term goals of the research funded by this grant has been to elucidate the molecular and cellular mechanisms by which CELLE affects brain development and impairs synaptic plasticity and cognitive function via NMDAR inhibition. Our current studies are defining molecular and cellular changes resulting from CELLE that resembles those associated with SZ. For example, CELLE results in the loss of parvalbumin-positive GABAergic interneurons (PVGI) in the frontal cortex and hippocampus of adolescent rats, neuropathology that is hallmark of SZ and is duplicated by NMDAR antagonist animal models of SZ. We also found that CELLE results in a hyperactive subcortical dopaminergic system and increases D2-dopamine receptor levels in the striatum, two features present in SZ subjects. The goal of the proposed studies is to determine the developmental trajectory of the PVGI loss produce by CELLE and the downstream effects on gamma oscillations (gamma-osc) and ultimately on cognitive function. We are focusing on PVGI because they are fast- spiking GABAergic inhibitory neurons that synchronize pyramidal cell firing, giving rise to gamma-osc that are critical for cognitive functio and PVGI development depends on NMDAR function. The proposed gamma-osc studies will provide a neural network link to the PVGI loss and behavioral and cognitive function deficits in adolescent and young adult Pb2+-exposed rats. We also propose to test D-serine as a pharmacological therapy that may mitigate the behavioral and cognitive function deficits resulting from early life Pb2+ intoxication. At the present time there is no pharmacological intervention that mitigates the behavioral and learning deficits resulting from Pb2+ intoxication i children.


Issue Date FY	Funding FY	Legal Entity Name	Legal Entity Address	Legal Entity City	Legal Entity State	Legal Entity Zip Code	Legal Entity COUNTY	Legal Entity COUNTRY	Assistance Listing	Award Code	Budget Year	Action Date	Action Type	Action Amount

Issue Date FY: 2022 ( Subtotal = -$1 )
2022	2019	FLORIDA INTERNATIONAL UNIVERSITY	11200 SW 8TH ST	MIAMI	FL	33199	MIAMI-DADE	USA	Environmental Health	000	25	11/28/2021	NON-COMPETING CONTINUATION	-$1
														Subtotal = -$1

Issue Date FY: 2019 ( Subtotal = $514,857 )
2019	2019	FLORIDA INTERNATIONAL UNIVERSITY	11200 SW 8TH ST	MIAMI	FL	33199	MIAMI-DADE	USA	Environmental Health	000	25	7/12/2019	NON-COMPETING CONTINUATION	$514,857
														Subtotal = $514,857

Issue Date FY: 2018 ( Subtotal = $932,591 )
2018	2018	FLORIDA INTERNATIONAL UNIVERSITY	11200 S W 8TH ST MARC 430	MIAMI	FL	33199	MIAMI-DADE	USA	Environmental Health	001	24	8/29/2018	SUPPLEMENT FOR EXPANSION	$366,250
2018	2018	FLORIDA INTERNATIONAL UNIVERSITY	11200 S W 8TH ST MARC 430	MIAMI	FL	33199	MIAMI-DADE	USA	Environmental Health	000	24	6/19/2018	NON-COMPETING CONTINUATION	$566,341
														Subtotal = $932,591

Issue Date FY: 2017 ( Subtotal = $570,256 )
2017	2017	FLORIDA INTERNATIONAL UNIVERSITY	11200 S W 8TH ST MARC 430	MIAMI	FL	33199	MIAMI-DADE	USA	Environmental Health	000	23	6/21/2017	NON-COMPETING CONTINUATION	$570,256
														Subtotal = $570,256

Issue Date FY: 2016 ( Subtotal = $577,800 )
2016	2016	FLORIDA INTERNATIONAL UNIVERSITY	11200 SW 8TH STREET	MIAMI	FL	33199	MIAMI-DADE	USA	Environmental Health	000	22	8/5/2016	CHANGE OF GRANTEE / TRAINING INSTITUTION / AWARDING INSTITUTION	$577,800
														Subtotal = $577,800

Issue Date FY: 2015 ( Subtotal = $597,813 )
2015	2015	COLUMBIA UNIVERSITY	615 WEST 131ST ST, 4TH FLOOR	NEW YORK	NY	10027	NEW YORK	USA	Environmental Health	002	21	7/31/2015	COMPETING CONTINUATION	$597,813
2015	2013	COLUMBIA UNIVERSITY	615 WEST 131ST ST, 4TH FLOOR	NEW YORK	NY	10027	NEW YORK	USA	Environmental Health	001	20	7/28/2015	NON-COMPETING CONTINUATION	$0
2015	2013	COLUMBIA UNIVERSITY	615 WEST 131ST ST, 4TH FLOOR	NEW YORK	NY	10027	NEW YORK	USA	Environmental Health	000	20	6/3/2015	NON-COMPETING CONTINUATION	$0
														Subtotal = $597,813

Issue Date FY: 2013 ( Subtotal = $491,695 )
2013	2013	COLUMBIA UNIVERSITY	615 WEST 131ST ST, 4TH FLOOR	NEW YORK	NY	10027	NEW YORK	USA	Environmental Health	000	20	6/17/2013	NON-COMPETING CONTINUATION	$491,695
														Subtotal = $491,695

Issue Date FY: 2012 ( Subtotal = $600,653 )
2012	2012	COLUMBIA UNIVERSITY	615 WEST 131ST ST, 4TH FLOOR	NEW YORK	NY	10027	NEW YORK	USA	Environmental Health	000	19	5/25/2012	NON-COMPETING CONTINUATION	$600,653
														Subtotal = $600,653

Issue Date FY: 2011 ( Subtotal = $886,029 )
2011	2011	COLUMBIA UNIVERSITY	615 WEST 131ST ST, 4TH FLOOR	NEW YORK	NY	10027	NEW YORK	USA	Environmental Health	000	18	6/4/2011	NON-COMPETING CONTINUATION	$886,029
														Subtotal = $886,029

Issue Date FY: 2010 ( Subtotal = $837,984 )
2010	2010	COLUMBIA UNIVERSITY	615 WEST 131ST ST, 4TH FLOOR	NEW YORK	NY	10027	NEW YORK	USA	Environmental Health	004	17	9/24/2010	SUPPLEMENT FOR EXPANSION	$329,051
2010	2010	COLUMBIA UNIVERSITY	615 WEST 131ST ST, 4TH FLOOR	NEW YORK	NY	10027	NEW YORK	USA	Environmental Health	003	17	9/22/2010	SUPPLEMENT FOR EXPANSION	-$329,051
2010	2010	COLUMBIA UNIVERSITY	615 WEST 131ST ST, 4TH FLOOR	NEW YORK	NY	10027	NEW YORK	USA	Environmental Health	002	17	9/21/2010	SUPPLEMENT FOR EXPANSION	$329,051
2010	2010	COLUMBIA UNIVERSITY	615 WEST 131ST ST, 4TH FLOOR	NEW YORK	NY	10027	NEW YORK	USA	Environmental Health	000	17	9/15/2010	CHANGE OF GRANTEE / TRAINING INSTITUTION / AWARDING INSTITUTION	$508,933
2010	2009	JOHNS HOPKINS UNIVERSITY	CHARLES & 34TH STREETS	BALTIMORE	MD	21218	BALTIMORE CITY	USA	Environmental Health	001	16	9/15/2010	COMPETING CONTINUATION	$0
														Subtotal = $837,984

Issue Date FY: 2009 ( Subtotal = $413,905 )
2009	2009	JOHNS HOPKINS UNIVERSITY	CHARLES & 34TH STREETS	BALTIMORE	MD	21218	BALTIMORE CITY	USA	Environmental Health	002	16	9/24/2009	COMPETING CONTINUATION	$413,905
2009	2007	JOHNS HOPKINS UNIVERSITY	CHARLES & 34TH STREETS	BALTIMORE	MD	21218	BALTIMORE CITY	USA	Environmental Health	001	15	9/18/2009	NON-COMPETING CONTINUATION	$0
2009	2007	JOHNS HOPKINS UNIVERSITY	CHARLES & 34TH STREETS	BALTIMORE	MD	21218	BALTIMORE CITY	USA	Environmental Health	000	15	6/19/2009	NON-COMPETING CONTINUATION	$0
														Subtotal = $413,905

Issue Date FY: 2007 ( Subtotal = $395,591 )
2007	2007	JOHNS HOPKINS UNIVERSITY	CHARLES & 34TH STREETS	BALTIMORE	MD	21218	BALTIMORE CITY	USA	Environmental Health	000	15	6/8/2007	NON-COMPETING CONTINUATION	$395,591
														Subtotal = $395,591

Issue Date FY: 2006 ( Subtotal = $394,962 )
2006	2006	JOHNS HOPKINS UNIVERSITY	CHARLES & 34TH STREETS	BALTIMORE	MD	21218	BALTIMORE CITY	USA	Environmental Health	000	14	6/30/2006	NON-COMPETING CONTINUATION	$394,962
														Subtotal = $394,962

Issue Date FY: 2005 ( Subtotal = $392,685 )
2005	2005	JOHNS HOPKINS UNIVERSITY	CHARLES & 34TH STREETS	BALTIMORE	MD	21218	BALTIMORE CITY	USA	Environmental Health	000	13	6/16/2005	NON-COMPETING CONTINUATION	$392,685
														Subtotal = $392,685

Issue Date FY: 2004 ( Subtotal = $438,128 )
2004	2004	JOHNS HOPKINS UNIVERSITY	CHARLES & 34TH STREETS	BALTIMORE	MD	21218	BALTIMORE CITY	USA	Environmental Health	000	12	7/8/2004	NON-COMPETING CONTINUATION	$438,128
														Subtotal = $438,128

Issue Date FY: 2003 ( Subtotal = $423,656 )
2003	2003	JOHNS HOPKINS UNIVERSITY	CHARLES & 34TH STREETS	BALTIMORE	MD	21218	BALTIMORE CITY	USA	Environmental Health	000	11	9/12/2003	COMPETING CONTINUATION	$423,656
														Subtotal = $423,656

Issue Date FY: 2002 ( Subtotal = $261,334 )
2002	2002	JOHNS HOPKINS UNIVERSITY	CHARLES & 34TH STREETS	BALTIMORE	MD	21218	BALTIMORE CITY	USA	Environmental Health	000	10	11/28/2001	NON-COMPETING CONTINUATION	$261,334
														Subtotal = $261,334

Issue Date FY: 2001 ( Subtotal = $253,721 )
2001	2001	JOHNS HOPKINS UNIVERSITY	CHARLES & 34TH STREETS	BALTIMORE	MD	21218	BALTIMORE CITY	USA	Environmental Health	000	9	11/23/2000	NON-COMPETING CONTINUATION	$253,721
														Subtotal = $253,721

Issue Date FY: 2000 ( Subtotal = $277,979 )
2000	2000	JOHNS HOPKINS UNIVERSITY	CHARLES & 34TH STREETS	BALTIMORE	MD	21218	BALTIMORE CITY	USA	Environmental Health	000	8	12/3/1999	NON-COMPETING CONTINUATION	$277,979
														Subtotal = $277,979

Issue Date FY: 1999 ( Subtotal = $268,769 )
1999	1999	JOHNS HOPKINS UNIVERSITY	CHARLES & 34TH STREETS	BALTIMORE	MD	21218	BALTIMORE CITY	USA	Environmental Health	000	7	11/6/1998	NON-COMPETING CONTINUATION	$268,769
														Subtotal = $268,769

Issue Date FY: 1998 ( Subtotal = $293,435 ) (Continued on the next page)
Grand Total All Awards = $9,823,842

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NMDA Receptor Function in Lead Neurotoxicity

Award Number: R01ES006189

ORGANIZATION: NATIONAL INSTITUTE OF ENVIRONMENTAL HEALTH SCIENCES

OPDIV: NIH

AWARD CLASS: DISCRETIONARY

AWARD ACTIVITY TYPE: SCIENTIFIC/HEALTH RESEARCH (INCLUDES SURVEYS)

PERIOD OF PERFORMANCE START DATE: 12/01/1992

PERIOD OF PERFORMANCE END DATE: 06/30/2021

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