Monday, May 29, 2023 5/29/2023

Investigating the pathological consequences of seizure-induced activation of the HPA axis

Award Number: R01NS102937
ORGANIZATION: NATIONAL INSTITUTE OF NEUROLOGICAL DISORDERS AND STROKE
OPDIV: NIH
AWARD CLASS: DISCRETIONARY
AWARD ACTIVITY TYPE: SCIENTIFIC/HEALTH RESEARCH (INCLUDES SURVEYS)

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Project Summary It is widely-accepted by both clinicians and basic scientists that stress can trigger and worsen seizures in animal models and in patients with epilepsy through the actions of stress mediators. The body's physiological response to stress is mediated by the hypothalamic-pituitary-adrenal (HPA) axis. The majority of studies investigating the relationship between the HPA axis and epilepsy focus on the role of stress and the proconvulsant actions of corticosterone (cortisol in humans) and corticotropin-releasing hormone (CRH). Interestingly, our lab recently demonstrated that seizures themselves activate the HPA axis, forcing us to reevaluate the role of the HPA axis in epilepsy. These findings suggest that seizure-induced activation of the HPA axis may directly contribute to changes in seizure susceptibility. Further, hyperexcitability of the HPA axis is a hallmark feature of depression, implicating seizure-induced activation of the HPA axis in the comorbidity of depression and epilepsy. The overarching objective of the current study is to investigate the pathophysiological consequences of this seizure-induced activation of the HPA axis, investigating the impact on the process of epileptogenesis (Specific Aim 1), seizure activity in chronically epileptic mice (Specific Aim 2), and the role in the comorbid depression (Specific Aim 3). These Aims will determine whether seizure-induced activation of the HPA axis is culpable in worsening seizure activity, associated pathology, and depression-like behaviors in chronically epileptic mice.


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: 2023 ( Subtotal = $663,760 )
2023	2023	TRUSTEES OF TUFTS COLLEGE	136 HARRISON AVE	BOSTON	MA	02111	SUFFOLK	USA	Extramural Research Programs in the Neurosciences and Neurological Disorders	000	6	12/7/2022	COMPETING CONTINUATION	$620,309
2023	2023	TRUSTEES OF TUFTS COLLEGE	136 HARRISON AVE	BOSTON	MA	02111	SUFFOLK	USA	Extramural Research Programs in the Neurosciences and Neurological Disorders	001	6	3/28/2023	SUPPLEMENT FOR EXPANSION	$43,451


Issue Date FY: 2022 ( Subtotal = $0 )
2022	2021	TRUSTEES OF TUFTS COLLEGE	136 HARRISON AVE	BOSTON	MA	02111	SUFFOLK	USA	Extramural Research Programs in the Neurosciences and Neurological Disorders	000	5	8/15/2022	NON-COMPETING CONTINUATION	$0


Issue Date FY: 2021 ( Subtotal = $360,938 )
2021	2021	TRUSTEES OF TUFTS COLLEGE	136 HARRISON AVE	BOSTON	MA	02111	SUFFOLK	USA	Extramural Research Programs in the Neurosciences and Neurological Disorders	000	5	2/18/2021	NON-COMPETING CONTINUATION	$360,938


Issue Date FY: 2020 ( Subtotal = $360,938 )
2020	2020	TRUSTEES OF TUFTS COLLEGE	136 HARRISON AVE	BOSTON	MA	02111	SUFFOLK	USA	Extramural Research Programs in the Neurosciences and Neurological Disorders	000	4	3/18/2020	NON-COMPETING CONTINUATION	$360,938


Issue Date FY: 2019 ( Subtotal = $360,938 )
2019	2019	TRUSTEES OF TUFTS COLLEGE	136 HARRISON AVE	BOSTON	MA	02111	SUFFOLK	USA	Extramural Research Programs in the Neurosciences and Neurological Disorders	000	3	2/12/2019	NON-COMPETING CONTINUATION	$360,938


Issue Date FY: 2018 ( Subtotal = $360,938 )
2018	2018	TRUSTEES OF TUFTS COLLEGE	136 HARRISON AVE	BOSTON	MA	02111	SUFFOLK	USA	Extramural Research Programs in the Neurosciences and Neurological Disorders	000	2	2/19/2018	NON-COMPETING CONTINUATION	$324,844
2018	2018	TRUSTEES OF TUFTS COLLEGE	136 HARRISON AVE	BOSTON	MA	02111	SUFFOLK	USA	Extramural Research Programs in the Neurosciences and Neurological Disorders	001	2	5/8/2018	NON-COMPETING CONTINUATION	$36,094


Issue Date FY: 2017 ( Subtotal = $360,938 )
2017	2017	TRUSTEES OF TUFTS COLLEGE	136 HARRISON AVE	BOSTON	MA	02111	SUFFOLK	USA	Extramural Research Programs in the Neurosciences and Neurological Disorders	000	1	5/25/2017	NEW	$360,938


Grand Total All Awards = $2,468,450

Sum of Action Amount is $2,468,450;

Grand Total = $2,468,450

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Investigating the pathological consequences of seizure-induced activation of the HPA axis

Award Number: R01NS102937

ORGANIZATION: NATIONAL INSTITUTE OF NEUROLOGICAL DISORDERS AND STROKE

OPDIV: NIH

AWARD CLASS: DISCRETIONARY

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

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