# Demyelination is coupled to neuronal hyperexcitability leading to seizures

> **NIH NIH R01** · UNIVERSITY OF CALIFORNIA RIVERSIDE · 2021 · $40,594

## Abstract

Cognitive impairment occurs and is more prevalent during primary progressive MS[1]. While MS clinical
presentation is protean, epidemiological studies have revealed that MS patients are three to six times more likely
to develop epileptic seizures than the population at large. Excitotoxic neuronal damage in the hippocampus (and
other regions) is thought to be one of the causes for cognitive deficits in nearly 50% of multiple sclerosis (MS)
patients and could be due glutamate dyshomeostasis. Glutamate is a major excitatory neurotransmitter in the
mammalian CNS. Our recent published results have shown i) a decrease in inhibitory parvalbumin neurons of
chronic cuprizone-diet fed demyelinating mice (Lapato et al., 2016) and in the hippocampus of MS patients with
seizures (Lapato et al., 2020); ii) astrocyte glutamate uptake and water homeostasis are dysregulated in the
hippocampus of MS patients with seizures (Lapato et al., 2020)[4]. The objective of this application is to
understand how demyelination-induced loss of inhibitory neurons impacts hippocampal changes that lead to
learning and memory deficits. We hypothesize that chronic demyelination induces decrease in hippocampus PV
neurons and indices substantial changes in synaptic transmission involved in learning and memory. In aim 1: we
will determine chronic cuprizone diet-demyelination induced changes in long term potentiation by
electrophysiology in brain slices. In aim 2, we will examine synaptic changes during chronic demyelination in the
CA1 and striatum radiatum regions of the hippocampus. In aim 3, we will assess chronic demyelination induced
changes in learning and memory. We anticipate that this research will be transformative, as we will introduce to
the research community a functional and molecular mechanism for memory disorder due to demyelination.

## Key facts

- **NIH application ID:** 10396346
- **Project number:** 3R01NS111552-02S1
- **Recipient organization:** UNIVERSITY OF CALIFORNIA RIVERSIDE
- **Principal Investigator:** DEVIN K BINDER
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2021
- **Award amount:** $40,594
- **Award type:** 3
- **Project period:** 2021-07-01 → 2024-05-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10396346

## Citation

> US National Institutes of Health, RePORTER application 10396346, Demyelination is coupled to neuronal hyperexcitability leading to seizures (3R01NS111552-02S1). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/10396346. Licensed CC0.

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