Inner capillary diameter of hypothalamic paraventricular nucleus of female rat increases during lactation

Cortés-Sol, Albertina; Lara-García, Miguel; Alvarado, Mayvi; Hudson, Robyn; Berbel, Pere; Pacheco, Pablo

doi:10.1186/1471-2202-14-7

Cited by 10 publications

(9 citation statements)

References 55 publications

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“…Prevalence of HJ3.4-immunoreactive capillaries was analyzed on three coronal cross-sectional profiles through the brain cortex at the aforementioned anatomical levels and on three to four subsequent coronal cross-sectional profiles through the thalamus. Aβ immunopositive capillaries (defined as vessels with diameter < 8 μm [ 28 , 29 ]) were manually counted at 40× objective magnification and their number was expressed as n/mm 2 .…”

Section: Methodsmentioning

confidence: 99%

APOE Genotype Differentially Modulates Effects of Anti-Aβ, Passive Immunization in APP Transgenic Mice

Pankiewicz

Baquero-Buitrago

Sanchez

et al. 2017

Mol Neurodegeneration

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Background APOE genotype is the foremost genetic factor modulating β-amyloid (Aβ) deposition and risk of sporadic Alzheimer’s disease (AD). Here we investigated how APOE genotype influences response to anti-Aβ immunotherapy.MethodsAPPSW/PS1dE9 (APP) transgenic mice with targeted replacement of the murine Apoe gene for human APOE alleles received 10D5 anti-Aβ or TY11-15 isotype control antibodies between the ages of 12 and 15 months.ResultsAnti-Aβ immunization decreased both the load of fibrillar plaques and the load of Aβ immunopositive plaques in mice of all APOE backgrounds. Although the relative reduction in parenchymal Aβ plaque load was comparable across all APOE genotypes, APP/ε4 mice showed the greatest reduction in the absolute Aβ plaque load values, given their highest baseline. The immunization stimulated phagocytic activation of microglia, which magnitude adjusted for the post-treatment plaque load was the greatest in APP/ε4 mice implying association between the ε4 allele and impaired Aβ phagocytosis. Perivascular hemosiderin deposits reflecting ensued microhemorrhages were associated with vascular Aβ (VAβ) and ubiquitously present in control mice of all APOE genotypes, although in APP/ε3 mice their incidence was the lowest. Anti-Aβ immunization significantly reduced VAβ burden but increased the number of hemosiderin deposits across all APOE genotypes with the strongest and the weakest effect in APP/ε2 and APP/ε3 mice, respectively.ConclusionsOur studies indicate that APOE genotype differentially modulates microglia activation and Aβ plaque load reduction during anti-Aβ immunotherapy. The APOE ε3 allele shows strong protective effect against immunotherapy associated microhemorrhages; while, conversely, the APOE ε2 allele increases risk thereof.Electronic supplementary materialThe online version of this article (doi:10.1186/s13024-017-0156-1) contains supplementary material, which is available to authorized users.

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Section: Methodsmentioning

confidence: 99%

APOE Genotype Differentially Modulates Effects of Anti-Aβ, Passive Immunization in APP Transgenic Mice

Pankiewicz

Baquero-Buitrago

Sanchez

et al. 2017

Mol Neurodegeneration

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“…The PVN has been known for some time to have a denser vascular network than the surrounding tissue [ 11 – 13 , 30 , 31 ]. Only recently has evidence of plasticity in this vascular network started to emerge [ 14 , 32 , 33 ]. The current study expands on the characteristics of the unique vasculature within the PVN by examining sex differences in BBB components and the long-term consequences of maternal dex treatment of their offspring reared into adulthood.…”

Section: Discussionmentioning

confidence: 99%

“…This has been shown to modulate metabolic exchange between capillaries and the parenchyma [ 36 ]. Within the PVN, changes in capillary diameter have been proposed to increase blood flow in lactating female rats [ 32 ], although in vivo measurements would be difficult to obtain due to the depth within the central region of the brain. For astrocytes, female offspring of dex-treated mothers had a decrease in total astrocytes and astrocytes in proximity to blood vessels.…”

Section: Discussionmentioning

confidence: 99%

Embryonic Exposure to Dexamethasone Affects Nonneuronal Cells in the Adult Paraventricular Nucleus of the Hypothalamus

Frahm

Tobet

2017

Journal of the Endocrine Society

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Neurons in the paraventricular nucleus of the hypothalamus (PVN) integrate peripheral signals and coordinate responses that maintain numerous homeostatic functions. An excess of glucocorticoids during fetal development results in long-lasting consequences tied to disrupted PVN development. The PVN contains a distinct neuronal population and a threefold greater vascular density than the surrounding brain regions that prepubertally is reduced in offspring exposed to excess glucocorticoids in utero. This study expands the examination of sex-specific nonneuronal PVN composition by examining astrocytes, astrocytic endfeet, and pericytes. Blood-brain barrier (BBB) competency and composition were examined along with depressive-like behavior and hypothalamic-pituitary-adrenal function in male and female mice. For PVN vasculature, female offspring of vehicle (veh)-treated mothers had significantly more astrocytes and pericytes than male offspring from the same litters. Female offspring from dexamethasone (dex)-treated mothers had significantly lower levels of astrocytes than female offspring from veh-treated mothers, whereas male offspring from dex-treated mothers had greater levels of pericytes compared with veh-treated male offspring. Using the tail-suspension test, male and female offspring from dex-treated mothers had significantly shorter latencies to immobility, indicating an increase in depression-like behavior, and showed greater plasma corticosterone after restraint stress, which was significantly greater in female offspring from dex-treated mothers even after recovery. Therefore, in addition to long-term sex differences in cellular components of the BBB in the PVN that were differentially regulated by fetal glucocorticoid exposure, there were behavioral differences observed into early adulthood in a sex-specific manner.

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“…Overall, published pregnancy-and/or lactation-associated CNS changes generally consist of alterations in structure or gene expression (e.g. (Cortes-Sol et al, 2013;Meurisse et al, 2005;Shingo et al, 2003;Theodosis et al, 1986).…”

Section: Control Zd Control Zdmentioning

confidence: 99%

Adaptive resetting of tuberoinfundibular dopamine (TIDA) network activity during lactation in mice

Pérez

Ferraris

Lunteren

et al. 2019

Preprint

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ABSTRACTGiving birth triggers a wide repertoire of physiological and behavioural changes in the mother to enable her to feed and care for her offspring. These changes require coordination and are often orchestrated from the central nervous system, through as of yet poorly understood mechanisms. A neuronal population with a central role in puerperal changes is the tuberoinfundibular dopamine (TIDA) neurons that control release of the pituitary hormone, prolactin, which triggers key maternal adaptations, including lactation and maternal care. Here, we used Ca2+ imaging on mice from both sexes and whole-cell recordings on female mouse TIDA neurons in vitro to examine if they adapt their cellular and network activity according to reproductive state. In the high-prolactin state of lactation, TIDA neurons shift to faster membrane potential oscillations, a reconfiguration that reverses upon weaning. During the estrous cycle, however, which includes a brief, but pronounced, prolactin peak, oscillation frequency remains stable. An increase in the hyperpolarization-activated mixed cation current, Ih, possibly through unmasking as dopamine release drops during nursing, may explain the reconfiguration of TIDA rhythms. These findings identify a reversible plasticity in hypothalamic network activity that can serve to adapt the dam for motherhood.Significance StatementMotherhood requires profound behavioural and physiological adaptations to enable caring for offspring, but the underlying CNS changes are poorly understood. Here, we show that during lactation, neuroendocrine dopamine neurons, the “TIDA” cells that control prolactin secretion, reorganize their trademark oscillations to discharge in faster frequencies. Unlike previous studies, which typically have focused on structural and transcriptional changes during pregnancy and lactation, we demonstrate a functional switch in activity and one that, distinct from previously described puerperal modifications, reverses fully upon weaning. We further provide evidence that a specific conductance – Ih - may underlie the altered network rhythm. These findings identify a new facet of maternal brain plasticity at the level of membrane properties and consequent ensemble activity.

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Inner capillary diameter of hypothalamic paraventricular nucleus of female rat increases during lactation

Cited by 10 publications

References 55 publications

APOE Genotype Differentially Modulates Effects of Anti-Aβ, Passive Immunization in APP Transgenic Mice

APOE Genotype Differentially Modulates Effects of Anti-Aβ, Passive Immunization in APP Transgenic Mice

Embryonic Exposure to Dexamethasone Affects Nonneuronal Cells in the Adult Paraventricular Nucleus of the Hypothalamus

Adaptive resetting of tuberoinfundibular dopamine (TIDA) network activity during lactation in mice

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