---
title: "Regulation of structural and functional synapse density by…"
description: "L-threonate directly increases magnesium inside neurons, leading to more synapses and improved cognitive function, which explains why it's a key…"
url: "https://magellanlongevity.com/study/d27178134.md"
canonical: "https://magellanlongevity.com/study/d27178134.html"
html: "https://magellanlongevity.com/study/d27178134.html"
type: "study"
study_key: "d27178134"
journal: "Neuropharmacology"
year: 2016
pmid: "27178134"
doi: "10.1016/j.neuropharm.2016.05.006"
citations: 1
updated: 2026-09-02
author: "Gabriel Radu, DO"
author_credentials: "Physiatrist (PM&R). NY medical license 275110. NPI 1376861765."
publisher: "Magellan Longevity"
content_format: "markdown"
---

# Regulation of structural and functional synapse density by L-threonate through intraneuronal magnesium

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## Citation

| Field | Value |
| --- | --- |
| Journal | Neuropharmacology |
| Year | 2016 |
| PMID | [27178134](https://pubmed.ncbi.nlm.nih.gov/27178134/) |
| DOI | [10.1016/j.neuropharm.2016.05.006](https://doi.org/10.1016/j.neuropharm.2016.05.006) |
| Study key | d27178134 |

## Takeaway

L-threonate directly increases magnesium inside neurons, leading to more synapses and improved cognitive function, which explains why it's a key component of L-TAMS.

## The question

Does L-threonate directly elevate intraneuronal magnesium and regulate synapse density, and why is magnesium alone ineffective for enhancing learning and memory?

## Hypothesis

The study aims to understand the unique role of threonate, specifically if it acts directly to elevate intraneuronal Mg2+ and mediates the therapeutic effects of L-TAMS.

## Methods

The researchers investigated the effects of threonate in cultured hippocampal neurons and human neural stem cell-derived neurons. They measured intracellular Mg2+ concentration, NR2B-containing NMDAR expression, mitochondrial membrane potential (ΔΨm), and functional synapse density. They also examined the role of glucose transporters (GLUTs) in mediating threonate's effects and measured CSF threonate levels after oral L-TAMS treatment.

## Results

Threonate is naturally present in CSF, and oral L-TAMS elevated CSF threonate. In cultured hippocampal neurons, threonate treatment directly increased intracellular Mg2+ concentration. Threonate also upregulated NR2B-containing NMDAR expression, boosted mitochondrial membrane potential (ΔΨm), and increased functional synapse density. These effects were unique to threonate and mediated through glucose transporters (GLUTs). Threonate was equally effective at upregulating synapse density in human neural stem cell-derived neurons.

## Conclusion

Threonate directly elevates intraneuronal magnesium and regulates structural and functional synapse density through glucose transporters, explaining its essential role in L-TAMS for promoting cognitive abilities.

## Limitations

The abstract does not explicitly state any limitations of the study.

## Verbatim from the abstract

> L-TAMS restoring global cognitive abilities of older adults; increased functional synapse density

## Where this study is used on Magellan

This paper is one of the citations behind the evidence grade on the pages below. Grades are assigned from the published research and are independent of affiliate commissions.

| Compound or device | Evidence grade | Graded pages |
| --- | --- | --- |
| Magnesium L-Threonate | Emerging evidence | [Magnesium L-Threonate](https://magellanlongevity.com/p/127.md) |

## Reference

1. **Regulation of structural and functional synapse density by L-threonate through intraneuronal magnesium**
   Neuropharmacology 2016 · [PMID 27178134](https://pubmed.ncbi.nlm.nih.gov/27178134/) · [DOI 10.1016/j.neuropharm.2016.05.006](https://doi.org/10.1016/j.neuropharm.2016.05.006)

   > L-TAMS restoring global cognitive abilities of older adults; increased functional synapse density

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## Related on Magellan Longevity

- [Magnesium L-Threonate](https://magellanlongevity.com/p/127.md) — product graded on this and related evidence
- [Evidence: brain-penetrant magnesium](https://magellanlongevity.com/study/s127.md)
- [Longevity research map](https://magellanlongevity.com/longevity-research-map.html)
- [Evidence-based longevity supplements](https://magellanlongevity.com/longevity-supplements.md)

## Scope and disclosures

Educational information, not medical advice. Nothing here is intended to diagnose, treat, cure, or prevent any disease. Talk to your physician before starting any supplement or device, especially if you are pregnant, nursing, or taking medication.

Editorial firewall: evidence grades are assigned from the published research and are independent of any affiliate commission. As an Amazon Associate, Magellan Longevity earns from qualifying purchases.

Reviewed for accuracy by a board-certified physician (DO).