Reversal of Diabetes Insipidus in Brattleboro Rats: Intrahypothalamic Injection of Vasopressin mRNA
Abstract
Messenger RNAs occur within the axons of magnocellular hypothalamic neurons known to secrete oxytocin and vasopressin. In Brattleboro rats, which have a genetic mutation that renders them incapable of vasopressin expression and secretion and thus causes diabetes insipidus, injection into the hypothalamus of purified mRNAs from normal rat hypothalami or of synthetic copies of the vasopressin mRNA leads to selective uptake, retrograde transport, and expression of vasopressin exclusively in the magnocellular neurons. Temporary reversal of their diabetes insipidus (for up to 5 days) can be observed within hours of the injection. Intra-axonal mRNAs may represent an additional category of chemical signals for neurons.
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Exogenous mRNA can direct protein expression in vivo.
“Following initial studies in the early 1990s demonstrating that exogenous mRNA can direct protein expression in vivo, mRNA has emerged as a promising drug platform technology in recent years (Wolff et al, 1990; Jirikowski et al, 1992).”
From mRNA mediates passive vaccination against infectious agents, toxins, and tumors (2017) · cites this paper as Jirikowski et al, 1992
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- Authors
- Jirikowski, G. F., Sanna, P. P., Maciejewski-Lenoir, D., & Bloom, F. E.
- Affiliations
- Scripps Research Institute (US)
- ORCID
- Sanna, Pietro Paolo
- Venue
- Science
- Published
- 1992-02-21
- Volume
- 255
- Issue
- 5047
- Pages
- 996-998
- ISSN
- 0036-8075 (ISSN-L)
- 1095-9203
- OpenAlex
- W2082706052
- Cited by
- 282
- References
- 20
- Citations by year
- 2026: 15 · 2025: 27 · 2024: 35 · 2023: 36 · 2022: 32 · 2021: 31 · 2020: 5 · 2019: 12 · 2018: 6 · 2017: 6 · 2016: 5 · 2015: 6 · 2014: 3 · 2012: 3
- FWCI
- 17.86
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- Science (publishedVersion)
- PubMed (publishedVersion)
- Funders
- National Institutes of Health (5p01ns022347-08)
- National Institute of Mental Health (MH47680, P50MH047680)
- National Institute of Neurological Disorders and Stroke (NS 22347-03)
- Topics
- Social Sciences › Psychology › Social Psychology › Neuroendocrine regulation and behavior
- Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Neuropeptides and Animal Physiology
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Ion Transport and Channel Regulation
- Keywords
- diabetes insipidus, Brattleboro rats, vasopressin, mRNA injection, intrahypothalamic injection, magnocellular neurons, retrograde transport, axonal mRNA transport, neuronal gene expression, oxytocin, hypothalamus
- MeSH terms
- Animals, Arginine Vasopressin, Diabetes Insipidus, Hypothalamus, Rats, Brattleboro, RNA, Messenger, Water-Electrolyte Balance, Rats
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