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Node of Ranvier Environment in Alcohol Abuse

Award Number: R21AA031788
ORGANIZATION: NATIONAL INSTITUTE ON ALCOHOL ABUSE AND ALCOHOLISM
OPDIV: NIH
AWARD CLASS: DISCRETIONARY
AWARD ACTIVITY TYPE: SCIENTIFIC/HEALTH RESEARCH (INCLUDES SURVEYS)
PERIOD OF PERFORMANCE START DATE: 07/16/2026
PERIOD OF PERFORMANCE END DATE: 06/30/2028

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Node of Ranvier Environment in Alcohol Abuse - Significant alterations of brain connectivity in alcohol use disorders (AUDs) may result from disturbances of signal integration at the synaptic level in the gray matter. In addition, defective brain connectivity in AUDs may be affected by alcohol abuse-induced myelin disturbances along white matter (WM) myelinated axons, since myelin critically supports fast signal propagation and contributes to axon maintenance. However, a major source of signal propagation anomalies may also depend on changes in and around nodes of Ranvier (NRs), myelin-bare regions of myelinated axons, that are essential to the regeneration of action potentials (signals) conveyed by axons, and thus to connectivity. However, morphological and molecular alterations at NRs that may contribute to abnormal connectivity in AUDs still remain mostly unexplored despite the well- known centrality of NRs to signal propagation. This proposal will determine whether alcohol abuse in humans with AUDs, and in experimental rats, leads to alterations of NR morphology and of distribution of extracellular matrix molecules (ECMMs) that are crucial to assembly and maintenance of NRs. In a different psychiatric disorder, depression, and in animals with chronic stress, we have found that levels of two glial NR proteoglycans and neurofascin 186, and in NR length are changed in the PFC of an animal model and in human subjects with depression. Some glial disturbances in AUDs and its animal models are shared with stress and depression while others differ. However, AUDs more globally affect various brain regions, so we hypothesize that structural (reduced NR length) and molecular changes in the NR’s environment will be found in AUDs in both prefrontal and occipital cortical WM. However, we hypothesize that overexpression of some NR-associated proteoglycans in PFC, but not in the OCC, WM will increase while their suppression will decrease alcohol drinking in experimental rats. The hypotheses will be tested according to the following specific aims: Specific aim 1 : We will test the hypothesis that alcohol intake in rats significantly reduces extent of astrocyte processes and NR length, and alters levels of ECMMs and their partners at NRs in OFC and OCC WM. Specific aim 2: We will test the hypothesis that diagnosis of AUD in humans is associated with shorter NRs, reduced astrocyte processes contacting NRs and altered levels of astrocyte-related ECMMs and partner axonal proteins in OFC and OCC WM, but not in the WM of the occipital cortex. Specific aim 3: We will test the hypothesis that suppression of astrocytic ECMMs in OFC but not in OCC, results in decreased alcohol intake behavior in rats. If this research supports the hypothesis that glial-derived proteoglycans and axonal components of the NR environment are involved in cellular and behavioral pathology related to alcohol intake, future research in rodents will target the mechanisms and intracellular pathways that regulate NR components in brain circuits involved in AUDs, and the ability of alcohol- intake-reducing treatments to reverse WM neuropathology and behavioral effects of AUDs.


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 = $409,500 )
2026	2026	UNIVERSITY OF MISSISSIPPI MEDICAL CENTER	2500 N STATE ST	JACKSON	MS	39216	HINDS	USA	Alcohol Research Programs	000	1	7/27/2026	NEW	$412,125
2026	2026	UNIVERSITY OF MISSISSIPPI MEDICAL CENTER	2500 N STATE ST	JACKSON	MS	39216	HINDS	USA	Alcohol Research Programs	001	1	7/30/2026	NEW	-$2,625
														Subtotal = $409,500

Grand Total All Awards = $409,500

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Node of Ranvier Environment in Alcohol Abuse

Award Number: R21AA031788

ORGANIZATION: NATIONAL INSTITUTE ON ALCOHOL ABUSE AND ALCOHOLISM

OPDIV: NIH

AWARD CLASS: DISCRETIONARY

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

PERIOD OF PERFORMANCE START DATE: 07/16/2026

PERIOD OF PERFORMANCE END DATE: 06/30/2028

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