Role of astroglial TNFR2 in cognitive function in multiple sclerosis

Active Project Grant Awarded Last action

Award ID
F31NS147418
Recipient
Awarding agency
Obligated
$50,114

Award facts

Assistance listing
93.853 Extramural Research Programs in the Neurosciences and Neurological Disorders
Completion date 0% complete
Place of performance
Miami, FL 33136, USA

Award details come from USAspending.gov.

Description

As the agency reported it.

Abstract
Cognitive dysfunction is a major burden for people with multiple sclerosis (MS), who suffer from a wide spectrum of deficits (impaired information processing speed, attention, memory) that severely compromise their quality of life. Despite the high prevalence and societal impact, cognitive dysfunction in MS is understudied and its mechanisms poorly understood. As such, no treatments to limit cognitive decline and facilitate cognitive recovery in MS are available. This is a major unmet need. MS-associated cognitive dysfunction has been linked to impaired synaptic transmission and plasticity, processes that require the communication between neurons and glia, particularly astrocytes. A key modulator of synaptic transmission and plasticity is tumor necrosis factor (TNF), which functions via binding to two receptors, TNFR1 and TNFR2, both expressed in astrocytes. Astroglial TNFR1 is essential for proper synaptic transmission and plasticity in physiological conditions, but in experimental autoimmune encephalomyelitis (EAE), the widely used model of MS, TNFR1 activation leads to learning and memory deficits indicating that, in disease states, astroglial TNFR1 turns detrimental. Remarkably, whether astroglial TNFR2 also plays a role in synaptic function/plasticity and cognition in pathological conditions was never explored. To address this GAP in knowledge, i will induce EAE in transgenic mice with astrocyte-specific ablation and overexpression of TNFR2 (GFAPCREERT2:TNFRSF1BFL/FL mice gfaptta:TNFRSF1BTRE mice, respectively) generated in the brambilla lab. Based on previous studies and preliminary data, i hypothesize that TNFR2 has a beneficial role in preventing/counteracting cognitive dysfunction in EAE by regulating cell-cell communication processes at the basis of synaptic function and plasticity. I will address my hypothesis with two stand-alone and complementary approaches: 1) in vivo studies to elucidate the role of astroglial TNFR2 in synaptic function and cognition in EAE; 2) in vitro studies to determine the mechanisms by which astroglial TNFR2 regulates neuron-glia communication.

Quick answers

Who received award F31NS147418?

F31NS147418 was awarded to University Of Miami by National Institute of Neurological Disorders and Stroke (National Institutes of Health) on March 2, 2027.

How much is award F31NS147418 worth?

$50,114 has been obligated on F31NS147418.

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