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Folic Acid, B12, and Neurodevelopmental Risk

Award Number: R01HD107489
ORGANIZATION: NATIONAL INSTITUTE OF CHILD HEALTH AND HUMAN DEVELOPMENT
OPDIV: NIH
AWARD CLASS: DISCRETIONARY
AWARD ACTIVITY TYPE: SCIENTIFIC/HEALTH RESEARCH (INCLUDES SURVEYS)
PERIOD OF PERFORMANCE START DATE: 06/10/2022
PERIOD OF PERFORMANCE END DATE: 04/30/2027

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Folic Acid, B12, and Neurodevelopmental Risk - The research objective of this multidisciplinary proposal is to examine the neurodevelopmental, behavioral, and biochemical consequences of excessive and deficient folic acid supplementation in a preclinical model. In this context vitamin B12 deficiency, a micronutrient required for the folate cycle, will also be tested. Central to our investigation are structural defects of the cerebral cortex, the predominant site of maldevelopment in a range of neurodevelopmental disorders, including neuronal migration disorders, childhood epilepsy, intellectual disability, and autism spectrum disorders (ASD). In these conditions, changes in prenatal neurogenesis can be the principal cause of structural abnormalities, such as pathological brain size variation, cortical lamination defects, or defective cytoarchitectural integrity. Consequently, further investigating the genetic and environmental causes and consequences of dysregulated early neurogenesis is of key importance towards a better understanding of neurodevelopmental disorders and the conception of preventive strategies. In 1998, the Food and Drug Administration mandated the fortification of grain products with folic acid to reduce the incidence of neural tube defects, which in combination with rising supplementation has led to a substantial increase in folic acid intake in the US. Intriguingly, our preliminary work has confirmed that excess maternal folic acid intake can alter cortical developmental neurogenesis. The question that arises from these observations is can too much of a good thing be a bad thing? Could excess folic acid intake during pregnancy result in altered cortical neurogenesis causing cerebral structural defects with life-long consequences. This concept has obtained further relevance by recent reports from epidemiological studies that found a higher incidence of ASD cases born to mothers with highest folate levels in their blood. To comprehensively explore this question, we will administer folic acid under three different conditions, a reduced folate in excess, and both in combination with B12 deficiency to pregnant dams to create test groups of offspring that we will analyze with respect to neurodevelopmental outcomes and behavioral abnormalities associated with social, cognitive, and anxiety disorders. These studies will be accompanied by detailed biochemical investigations on brain folate pathway dysregulations, including folate transport, processing, and consequences for DNA methylation.


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: 2026 ( Subtotal = $443,445 )
2026	2026	UNIVERSITY OF CALIFORNIA, DAVIS	1850 RESEARCH PARK DR STE 300	DAVIS	CA	95618	YOLO	USA	Child Health and Human Development Extramural Research	000	5	4/24/2026	NON-COMPETING CONTINUATION	$443,445
														Subtotal = $443,445

Issue Date FY: 2025 ( Subtotal = $503,300 )
2025	2025	UNIVERSITY OF CALIFORNIA, DAVIS	1850 RESEARCH PARK DR STE 300	DAVIS	CA	95618	YOLO	USA	Child Health and Human Development Extramural Research	000	4	5/5/2025	NON-COMPETING CONTINUATION	$503,300
														Subtotal = $503,300

Issue Date FY: 2024 ( Subtotal = $505,049 )
2024	2024	UNIVERSITY OF CALIFORNIA, DAVIS	1850 RESEARCH PARK DR STE 300	DAVIS	CA	95618	YOLO	USA	Child Health and Human Development Extramural Research	000	3	4/30/2024	NON-COMPETING CONTINUATION	$505,049
														Subtotal = $505,049

Issue Date FY: 2023 ( Subtotal = $478,816 )
2023	2023	UNIVERSITY OF CALIFORNIA, DAVIS	1850 RESEARCH PARK DR, STE 300	DAVIS	CA	95618	YOLO	USA	Child Health and Human Development Extramural Research	000	2	5/24/2023	NON-COMPETING CONTINUATION	$478,816
														Subtotal = $478,816

Issue Date FY: 2022 ( Subtotal = $414,024 )
2022	2022	UNIVERSITY OF CALIFORNIA, DAVIS	1850 RESEARCH PARK DR, STE 300	DAVIS	CA	95618	YOLO	USA	Child Health and Human Development Extramural Research	000	1	6/10/2022	NEW	$414,024
2022	2022	UNIVERSITY OF CALIFORNIA, DAVIS	1850 RESEARCH PARK DR, STE 300	DAVIS	CA	95618	YOLO	USA	Child Health and Human Development Extramural Research	001	1	7/6/2022	NEW	$0
														Subtotal = $414,024

Grand Total All Awards = $2,344,634

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Folic Acid, B12, and Neurodevelopmental Risk

Award Number: R01HD107489

ORGANIZATION: NATIONAL INSTITUTE OF CHILD HEALTH AND HUMAN DEVELOPMENT

OPDIV: NIH

AWARD CLASS: DISCRETIONARY

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

PERIOD OF PERFORMANCE START DATE: 06/10/2022

PERIOD OF PERFORMANCE END DATE: 04/30/2027

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