Cited by 319Neuroendocrine regulation and behaviorCircadian rhythm and melatoninHypothalamic control of reproductive hormones

The DOI matches its Crossref record; 43 of the 46 references it cites were found in a registry or an index; none of the 8 sources its claims cite is checked for support yet.

Ontogeny of the vasopressinergic neurons of the suprachiasmatic nucleus and their extrahypothalamic projections in the rat brain–presence of a sex difference in the lateral septum

Open access
De Vries, Geert J., Buds, Ruud M., Swaab, Dick F.·1981·Brain Research

Abstract

Immunocytochemical studies have revealed the presence of extensive vasopressinergic projections from the suprachiasmatic nucleus to the limbic system and other brain areas. Vibratome sections and the unlabeled antibody enzyme method were used to investigate the ontogeny of the vasopressinergic neurons of the suprachiasmatic nucleus and their exohypothalamic fibers in the rat brain. The first immunopositive neurons of this nucleus were revealed on the 2nd postnatal day. An adult appearance of the suprachiasmatic nucleus was detected on day 14. Although fibers appeared on the periventricular nucleus already on the 7th postnatal day, such fibers were visible in the lateral septum and lateral habenular nucleus only on day 10. From the 12th postnatal day onwards a marked sex difference developed with respect to the density of the vasopressin fibers in the lateral septum and, to a lesser extent, in the lateral habenular nucleus. In male rats the fiber density was higher in both areas. This sex difference persisted in adulthood.

Overview

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Written from the paper’s full text.

TL;DR

Using immunocytochemistry on vibratome sections, this study traced the postnatal development of vasopressinergic (AVP) neurons in the rat suprachiasmatic nucleus (SCN) and their extrahypothalamic projections, finding the first AVP-positive SCN cells on postnatal day 2 and an adult-like nucleus by day 14. From postnatal day 12 onward a marked sex difference emerged, with male rats showing denser AVP fiber networks in the lateral septum and, less strikingly, the lateral habenular nucleus, persisting into adulthood.

Key findings

  • No AVP-positive cells were seen in the SCN on postnatal day 1; a few were detected in 1 of 3 two-day-old rats, in 6 of 8 rats on day 3, and in all animals from days 4–6. An adult appearance of the SCN was reached on day 14.
  • Fibers appeared in the periventricular nucleus by day 7, but were visible in the lateral septum and lateral habenular nucleus only on day 10.
  • From day 12 onward a sex difference developed in the density of AVP fibers in the lateral septum: in males density increased dramatically from day 12 to 17, whereas no such change occurred in females. In 55-day-old females the fiber number was still moderate, comparable to that of 12–14-day-old males; the difference persisted in adulthood but was less striking than between days 17 and 35.
  • A similar but weaker sex difference was seen in the lateral habenular nucleus (adult-like appearance in males by day 14, females by day 17), with considerable overlap between the sexes. No sex difference was noted in the SCN or periventricular nucleus.

Methods

  • Infant Wistar rats of either sex: first series studied on days 1–8, 10, 12, 14, 17 and 21 (3 rats per age group); second series sacrificed on days 3, 10, 12, 14, 17, 21, 27, 35 and 55 (2–6 rats of each sex per age group). Adults were 3 male and 3 female rats weighing 230–250 g.
  • Brains were perfused with glutaraldehyde/paraformaldehyde, sectioned with a vibratome, and stained for AVP using the unlabeled antibody enzyme (PAP) method; antibody specificity was tested by immunofluorescence and adsorption controls, including Brattleboro rats.
  • Fiber density in the lateral septum and lateral habenular nucleus was estimated semi-quantitatively in a blind study using 4 categories (+, ++, +++, ++++).

Limitations

  • The paper states that its procedure "was not suited to a quantitative approach," so a sex difference in the number of AVP-containing cells cannot be excluded; it also notes that how the observed sex differences relate to functional differences remains speculative.
  • Evident from the text: fiber density was scored only semi-quantitatively on an ordinal scale, group sizes were small (2–6 rats per sex per age), and large individual variation was noted, particularly in the lateral habenular nucleus where overlap between sexes was considerable.

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Integrity signals

Registry

Crossref · 10.1016/0006-8993(81)90989-6

Cites

43 of 43 references verified0 citation errors · 0 not checkable

Statistics

Nothing to recompute.

Verification

Claims the paper makes

29 Own result · 9 Own interpretation · 5 No full text of the sources · 2 Own method

Show all 22 claims

  • It may state two separate claims as one. 15
  • The quote only partly states this claim. 2
  • Probably not a substantial claim. 7
23 of 23
  • The paper relies on this without support.

    The stage of the estrous cycle does not affect the density of AVP-containing fibers in the lateral septum of female rats.

    “The stages of the estrous cycle of the female rats were proestrus, estrus and metestrus.”
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Citations

Cites

Show all 46 references

Research works printed but not linked: 2

  1. Boer, 1980, Neuropeptides in brain development, Vol. 54
  2. Moore, 1978, Central neural control of circadian rhythms, Front. Neuroendocr., 5, 185

Cited by

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Metadata

Authors
De Vries, G. J., Buds, R. M., & Swaab, D. F.
Venue
Brain Research
Publisher
Elsevier BV
Published
1981-08
Volume
218
Issue
1-2
Pages
67-78
ISSN
0006-8993 (ISSN-L)
OpenAlex
W2002833231
Cited by
319
References
46
Citations by year
2026: 5 · 2025: 3 · 2024: 2 · 2023: 2 · 2022: 8 · 2021: 10 · 2020: 1 · 2019: 7 · 2018: 14 · 2017: 9 · 2016: 7 · 2015: 5 · 2014: 11 · 2013: 4 · 2012: 4
FWCI
21.77
Type
journal article
Language
en
Open access
Locations
  • Brain Research (publishedVersion)
  • PubMed (publishedVersion)
  • KNAW research portal (Royal Academy of Art and Sciences (KNAW)) (submittedVersion)
  • Data Archiving and Networked Services (DANS) (submittedVersion, other-oa)
  • KNAW Research Portal (The Royal Netherlands Academy of Arts and Sciences) (submittedVersion)
Topics
  • Life Sciences › Neuroscience › Endocrine and Autonomic Systems › Neuroendocrine regulation and behavior
  • Life Sciences › Neuroscience › Endocrine and Autonomic Systems › Circadian rhythm and melatonin
  • Health Sciences › Medicine › Reproductive Medicine › Hypothalamic control of reproductive hormones
Keywords
vasopressin, suprachiasmatic nucleus, ontogeny, sex differences, lateral septum, lateral habenula, limbic system, postnatal development, rat brain
MeSH terms
Animals, Female, Hypothalamus, Immunoenzyme Techniques, Male, Neurons, Sex Characteristics, Vasopressins, Rats

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