A study of the role of neuro-glial remodeling in the oxytocin system at lactation

doi:10.1016/j.neuroscience.2005.08.042

Neuroscience

Volume 137, Issue 1, 2006, Pages 309-316

https://doi.org/10.1016/j.neuroscience.2005.08.042 Get rights and content

Abstract

Under conditions of strong secretion of neurohypophysial hormone, such as during parturition, lactation and dehydration, the hypothalamic oxytocin-system displays a remarkable morphological plasticity such that astrocytic coverage of its neurones diminishes, their surfaces become directly juxtaposed and contacted by an increased number of synapses. A growing body of evidence indicates that these anatomical changes have an impact on glutamatergic neurotransmission in the supraoptic nucleus, and may be therefore of physiological consequence. We here evaluated the consequences of the inhibition of such plasticity on the overall activity of the oxytocin system during lactation. Remodeling was prevented by performing hypothalamic microinjections in gestating rats of endoneuraminidase, an enzyme that removes polysialic acid from the neural cell adhesion molecule. Our earlier studies established that the presence of polysialic acid is a prerequisite for remodeling of the oxytocin system in the supraoptic and paraventricular nuclei. In dams in which polysialic acid was absent in all magnocellular nuclei after bilateral endoneuraminidase injections, parturition was normal and neither the frequency nor the amplitude of suckling-induced reflex milk ejections was different from vehicle-treated dams. The weight gain of pups was also normal as was water intake by the dams. We then assessed the electrical activity of antidromically identified magnocellular neurones in the polysialic acid-free supraoptic nucleus of isoflurane-anesthetized lactating rats. Basal and bursting activity characteristic of oxytocin neurones before each reflex milk ejection was not significantly different from that recorded in the supraoptic nucleus of rats with normal levels of polysialic acid. Our results indicate that neuro-glial remodeling, despite its role on fine modulation of oxytocin neuronal activity, is not essential to parturition and lactation.

Section snippets

Animals

Female Wistar rats, at least 3 months of age, and raised under controlled temperature and light conditions (12-h light/dark; water and food ad libitum) were used (n=55). They were mated and pregnancy was confirmed by the presence of a vaginal plug on the next day (gestation day 0); they were then housed in individual cages. All experiments were carried out according to international guidelines on the ethical use of animals. Moreover, the protocol elaborated here was such as to limit the number

PSA in the hypothalamus and its removal by endoN

In accord with earlier studies (Theodosis et al 1991, Theodosis et al 1999, Bonfanti et al 1992), in the aCSF-treated group, we found strong immunoreactivity for PSA in the SON and PVN, around the third ventricle and very little in adjacent hypothalamic areas (Fig. 1A). PSA immunoreactivity characteristically filled the neuropil around neuronal somata, which were immunonegative. In endoN-treated animals, a single microinjection of endoN resulted in variable diffusion of the enzyme and PSA was

Discussion

As in earlier studies (Theodosis et al 1991, Theodosis et al 1999), we observed a large amount of the carbohydrate PSA in the hypothalamic magnocellular nuclei of aCSF-treated animals, which was completely removed in endoN-treated animals. Our earlier ultrastructural studies established that enzymatic removal of PSA with endoN prevents the onset of morphological plasticity throughout the OT system (Theodosis et al 1999, Monlezun et al 2005). We showed in this study that endoN removal of PSA and

Acknowledgments

We are grateful to G. Rougon (Marseille, France) for her generous gifts of PSA-NCAM antibody and endoN enzyme. This work was supported by a Région Aquitaine contract (no. 200103 01 220).

References (40)

L. Bonfanti et al.
Mapping of the distribution of polysialylated neural cell adhesion molecule throughout the central nervous system of the adult ratan immunohistochemical study
Neuroscience
(1992)
S. Monlezun et al.
Polysialic acid is required for active phases of morphological plasticity of neurosecretory axons and their glia
Mol Cell Neurosci
(2005)
D. Muller et al.
PSA-NCAM is required for activity-induced synaptic plasticity
Neuron
(1996)
K. Pierre et al.
The polysialylated neural cell adhesion molecule reaches cell surfaces of hypothalamic neurons and astrocytes via the constitutive pathway
Neuroscience
(2001)
U. Rutishauser et al.
Polysialic acid in the vertebrate nervous systema promoter of plasticity in cell-cell interactions
Trends Neurosci
(1996)
S.Y. Shu et al.
The glucose oxidase-DAB-nickel method in peroxidase histochemistry of the nervous system
Neurosci Lett
(1988)
D.T. Theodosis
Oxytocin-secreting neuronsA physiological model of morphological neuronal and glial plasticity in the adult hypothalamus
Front Neuroendocrinol
(2002)
D.T. Theodosis et al.
Neuronal, glial and synaptic remodeling in the adult hypothalamusfunctional consequences and role of cell surface and extracellular matrix adhesion molecules
Neurochem Int
(2004)
D.S. Auld et al.
Modulation of neurotransmission by reciprocal synapse-glial interactions at the neuromuscular junction
J Neurocytol
(2003)
C.G. Becker et al.
The polysialic acid modification of the neural cell adhesion molecule is involved in spatial learning and hippocampal long-term potentiation
J Neurosci Res
(1996)

A.B. Brussaard et al.

Changes in properties and neurosteroid regulation of GABAergic synapses in the supraoptic nucleus during the mammalian female reproductive cycle

J Physiol

(1999)

D.A. Carter et al.

Oxytocin responses to stress in lactating and hyperprolactinaemic rats

Neuroendocrinology

(1987)

S. Di et al.

Dehydration-induced synaptic plasticity in magnocellular neurons of the hypothalamic supraoptic nucleus

Endocrinology

(2004)

P. Durbec et al.

Revisiting the function of PSA-NCAM in the nervous system

Mol Neurobiol

(2001)

M.J. Freund-Mercier et al.

Electrophysiological evidence for facilitatory control of oxytocin neurones by oxytocin during suckling in the rat

J Physiol

(1984)

R.D. Hartman et al.

Endogenous opioid peptides inhibit oxytocin release in the lactating rat after dehydration and urethane

Endocrinology

(1987)

T. Higuchi et al.

Reduced oxytocin response to osmotic stimulus and immobilization stress in lactating rats

J Endocrinol

(1988)

J.M. Israel et al.

Glutamatergic input governs periodicity and synchronization of bursting activity in oxytocin neurons in hypothalamic organotypic cultures

Eur J Neurosci

(2003)

P. Jourdain et al.

Evidence for a hypothalamic oxytocin-sensitive pattern-generating network governing oxytocin neurons in vitro

J Neurosci

(1998)

S. Kaufman

Control of fluid intake in pregnant and lactating rats

J Physiol

(1981)

Cited by (39)

The hypothalamic paraventricular nucleus as a central hub for the estrogenic modulation of neuroendocrine function and behavior
2022, Frontiers in Neuroendocrinology
Citation Excerpt :
In addition, glial cells release different gliotransmitters, such as ATP, adenosine, glutamate and D-serine that modulate synaptic transmission and participate in the processing of neuronal information (Oliet et al., 2001; Panatier et al., 2006; Perea et al., 2009; Tasker et al., 2012). In the hypothalamus, changes in astrocytic coverage of magnocellular neurons in the PVN and the supraoptic nucleus are associated with OXT neuron bursting and with changes in the number and function of synaptic contacts on OXT cells (Catheline et al., 2006; Oliet et al., 2001; Tasker et al., 2012; Theodosis et al., 1981; Tweedle and Hatton, 1977). In addition, inflammatory activation of astrocytes and microglia of the PVN is associated with sympathetic activation and the development of hypertension (Ahmari et al., 2019; Mi et al., 2018; Moreira et al., 2019).
Estradiol and hypothalamic paraventricular nucleus (PVN) help coordinate reproduction with body physiology, growth and metabolism. PVN integrates hormonal and neural signals originating in the periphery, generating an output mediated both by its long-distance neuronal projections, and by a variety of neurohormones produced by its magnocellular and parvocellular neurosecretory cells. Here we review the cyto-and chemo-architecture, the connectivity and function of PVN and the sex-specific regulation exerted by estradiol on PVN neurons and on the expression of neurotransmitters, neuromodulators, neuropeptides and neurohormones in PVN. Classical and non-classical estrogen receptors (ERs) are expressed in neuronal afferents to PVN and in specific PVN interneurons, projecting neurons, neurosecretory neurons and glial cells that are involved in the input–output integration and coordination of neurohormonal signals. Indeed, PVN ERs are known to modulate body homeostatic processes such as autonomic functions, stress response, reproduction, and metabolic control. Finally, the functional implications of the estrogenic modulation of the PVN for body homeostasis are discussed.
Oxytocin: Control of secretion by the brain and central roles
2016, The Curated Reference Collection in Neuroscience and Biobehavioral Psychology
Oxytocin is a nonapeptide produced by hypothalamic neurons, some of which project to the posterior pituitary, and others have targets in brain and spinal cord. Oxytocin secretion is important in parturition and essential for lactation. Oxytocin peptide and receptor gene regulation by sex steroids is described. The oxytocin receptor and post-receptor metabotropic pathways are detailed. Neural circuits controlling oxytocin neurons, transmitters they use and patterns of oxytocin secretion generated are described. Promotion by oxytocin in the brain of behaviors and emotionality conducive to reproduction and social interaction is critically reviewed. Possible consequences of derangement of central oxytocin functions are discussed.
Maternal Brain Adaptations in Pregnancy
2015, Knobil and Neill's Physiology of Reproduction: Two-Volume Set
During pregnancy multiple physiological adaptations take place in the mother to optimize the chances of a successful pregnancy outcome. These adaptations play a critical role in reproductive physiology, serving to (1) increase the supply of oxygen and nutrients to the placenta and maternal organs supporting the pregnancy; (2) optimize fetal growth and development; (3) prepare expanded oxytocin stores for when they are in demand at parturition and for lactation; (4) protect the pregnancy from premature birth; (5) protect the fetus from adverse programming, e.g., by maternal stress; (6) ensure adequate milk production and delivery at lactation; and (7) ensure that the appropriate brain circuits are primed and behaviors altered to deliver sufficient maternal care after parturition. In this chapter we focus on these pregnancy-related adaptations that are organized by the maternal brain, many of which are induced by the increased levels of pregnancy hormones.
Neuropeptides as neuroprotective agents: Oxytocin a forefront developmental player in the mammalian brain
2014, Progress in Neurobiology
Citation Excerpt :
OT and AVP which belong to the same posterior pituitary hormone family, are secreted into the blood stream from axons terminals or into the brain from dendrites of hypothalamic neurons (Bondy et al., 1989; Caldwell et al., 2008; Hatton, 1996; Ludwig and Leng, 2006; Widmer et al., 2003), under modulation of a special set of Ca2+-sensors or synaptogmins (Iezzi et al., 2005; Südhof, 2004; Xu et al., 2007a). These peptides regulate the function of peripheral target organs, such as uterine contraction, lactation, penile erection, and urine concentration (Melis et al., 2007; Bernal et al., 2007; Catheline et al., 2006; Febo et al., 2005). Thus OT is involved in supporting uterine contractions throughout labor, newborn brain neuroprotection and ejection of milk during lactation (Gimpl and Fahrenholz, 2001; Tyzio et al., 2006; Wang and Hatton, 2007b).
Oxytocin (OT) plays a major role in the establishment of social bonds. Social bonds are linked to the activation of cell signaling pathways that promote neurotrophic and synaptic maturation, plasticity and memory changes. Anti-social behavior is often associated with abnormalities of cell signaling pathways and/or defective function of brain neurotransmitters within behavioral CNS circuits due to unproper environmental and social factors, such as, diet, stress, chemical, air pollution, and noise, during gestational period or/and during early postnatal development.
OT exerts an important regulatory functions in maternity and parental behaviors, lactation, attachment, bonding, trust, and sensorial functions such as: homeostatic cardiovascular control, satiety, touch, pain, analgesia and sexual behavior. Noteworthy, OT displays important neuroprotective properties against fetal programmed hypertension when administered during early postnatal life, added to its known anabolic properties shown in adult rats, e.g. body weight control, reduces blood pressure, and increases analgesia. This review focuses on the new evidences supporting OT's role as a major neuroprotective nonapeptide provided by its quality to reverse hypertension programmed in utero by undernutrition.
Changes in the content of GFAP in the rat brain during pregnancy and the beginning of lactation
2010, Neuroscience Letters
Several changes in brain function, including learning and memory, have been reported during pregnancy but the molecular mechanisms involved in these changes are unknown. Due to the fundamental role of glial cells in brain activity, we analyzed the content of glial fibrillary acidic protein (GFAP) in the hippocampus, frontal cortex, preoptic area, hypothalamus and cerebellum of the rat on days 2, 14, 18, and 21 of pregnancy and on day 2 of lactation by Western blot. A differential expression pattern of GFAP was found in the brain during pregnancy and the beginning of lactation. GFAP content was increased in the hippocampus throughout pregnancy, whereas a decrease was observed in cerebellum. GFAP content was increased in the frontal cortex and hypothalamus on days 14 and 18, respectively, with a decrease in the following days of pregnancy in both regions. In preoptic area a decrease in GFAP content was observed on day 14 with an increase on days 18 and 21. In the frontal cortex and cerebellum, GFAP content was increased on day 2 of lactation, while it was maintained as on day 21 of pregnancy in the other regions. Our data suggest a differential expression pattern of GFAP in the rat brain during pregnancy and the beginning of lactation that should be associated with changes in brain function during these reproductive stages.
The cell biology of oxytocin and vasopressin cells
2010, Hormones, Brain and Behavior Online
Oxytocin (OT) and vasopressin (VP) are neuropeptides synthesized principally by magnocellular neurons in the hypothalamus. It was seen over 50 years ago that these cells possess both neuronal and endocrine properties. They comprise the hypothalamo-neurohypophysial system (HNS) whose anatomy makes possible ready analysis of electrophysiological, biosynthetic, and secretory activities during vital physiological conditions like parturition, lactation, and osmotic and cardiovascular regulation. The somata and dendrites of the neurons accumulate in well-delineated hypothalamic areas, the paired supraoptic and paraventricular nuclei. Their axons project to the neurohypophysis where OT and VP are released by exocytosis directly into the bloodstream to act as hormones on several peripheral organs. Additionally, the neuropeptides are secreted via a somato-dendritic exocytotic mechanism within the magnocellular nuclei where they autoregulate their own systems. They are also released from axon terminals in other areas of the nervous system to act as neurotransmitters or neuromodulators in a variety of limbic and autonomic functions. The HNS, and in particular, its oxytocinergic component, possesses a remarkable capacity for activity-dependent morphological plasticity which modulates its electrophysiological and secretory activities further. These neuroendocrine populations thus represent excellent models for the study of state-dependent cell biology of neurosecretion.

View all citing articles on Scopus

View full text

Systems neuroscienceA study of the role of neuro-glial remodeling in the oxytocin system at lactation

Abstract

Section snippets

Animals

PSA in the hypothalamus and its removal by endoN

Discussion

Acknowledgments

Neuroscience

Mol Cell Neurosci

Neuron

Neuroscience

Trends Neurosci

Neurosci Lett

Front Neuroendocrinol

Neurochem Int

Modulation of neurotransmission by reciprocal synapse-glial interactions at the neuromuscular junction

J Neurocytol

The polysialic acid modification of the neural cell adhesion molecule is involved in spatial learning and hippocampal long-term potentiation

J Neurosci Res

Changes in properties and neurosteroid regulation of GABAergic synapses in the supraoptic nucleus during the mammalian female reproductive cycle

J Physiol

Oxytocin responses to stress in lactating and hyperprolactinaemic rats

Neuroendocrinology

Dehydration-induced synaptic plasticity in magnocellular neurons of the hypothalamic supraoptic nucleus

Endocrinology

Revisiting the function of PSA-NCAM in the nervous system

Mol Neurobiol

Electrophysiological evidence for facilitatory control of oxytocin neurones by oxytocin during suckling in the rat

J Physiol

Endogenous opioid peptides inhibit oxytocin release in the lactating rat after dehydration and urethane

Endocrinology

Reduced oxytocin response to osmotic stimulus and immobilization stress in lactating rats

J Endocrinol

Glutamatergic input governs periodicity and synchronization of bursting activity in oxytocin neurons in hypothalamic organotypic cultures

Eur J Neurosci

Evidence for a hypothalamic oxytocin-sensitive pattern-generating network governing oxytocin neurons in vitro

J Neurosci

Control of fluid intake in pregnant and lactating rats

J Physiol

Systems neuroscience
A study of the role of neuro-glial remodeling in the oxytocin system at lactation