Structural Reconstruction of the Perivascular Space in the Adult Mouse Neurohypophysis During an Osmotic Stimulation

Nishikawa, Kazunori; Furube, Eriko; Morita, Shoko; Horii-Hayashi, Noriko; Nishi, Mayumi; Miyata, Seiji

doi:10.1111/jne.12456

Cited by 10 publications

(33 citation statements)

References 69 publications

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“…Although pericytes have been previously reported to be associated with neurohypophyseal capillaries (Miyata, 2017;Nishikawa et al, 2017), we did not detect them in the present study, possibly due to the fact that isolating pericytes requires different tissue dissociation conditions. It is also possible that other minor neurohypophyseal cell populations have been missed, which may be revealed if more cells would be sampled.…”

Section: Discussioncontrasting

confidence: 83%

Single-Cell Molecular and Cellular Architecture of the Mouse Neurohypophysis

Chen

Leshkowitz

Blechman

et al. 2020

eNeuro

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The neurohypophysis (NH), located at the posterior lobe of the pituitary, is a major neuroendocrine tissue, which mediates osmotic balance, blood pressure, reproduction, and lactation by means of releasing the neurohormones oxytocin (OXT) and arginine-vasopressin (AVP) from the brain into the peripheral blood circulation. The major cellular components of the NH are hypothalamic axonal termini, fenestrated endothelia and pituicytes, the resident astroglia. However, despite the physiological importance of the NH, the exact molecular signature defining neurohypophyseal cell types and in particular the pituicytes, remains unclear. Using single-cell RNA sequencing (scRNA-Seq), we captured seven distinct cell types in the NH and intermediate lobe (IL) of adult male mouse. We revealed novel pituicyte markers showing higher specificity than previously reported. Bioinformatics analysis demonstrated that pituicyte is an astrocytic cell type whose transcriptome resembles that of tanycyte. Single molecule in situ hybridization revealed spatial organization of the major cell types implying intercellular communications. We present a comprehensive molecular and cellular characterization of neurohypophyseal cell types serving as a valuable resource for further functional research.

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Section: Discussioncontrasting

confidence: 83%

Single-Cell Molecular and Cellular Architecture of the Mouse Neurohypophysis

Chen

Leshkowitz

Blechman

et al. 2020

eNeuro

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“…The expression of collagen I is stronger at the inner BM than at the outer BM, whereas that of laminin is stronger at the outer BM than at the inner BM in these regions ( 23 , 28 ). Moreover, the inner and outer BMs are both thicker in these neurosecretory brain regions than in other typical brain regions [( 23 ); Figure 2 ].…”

Section: Size-limited Vascular Permeabilitymentioning

confidence: 97%

“…Alternatively, ECs express many kinds of transporter proteins on the luminal side of the EC membrane, which allow for the direct incorporation of amino acids, vitamins, hormones, proteins, or other compounds of the blood ( 22 ). However, the vasculature lacks the expression of tight junction proteins on ECs in the NH ( 23 ) and ME ( 24 – 26 ). Since there are no neuronal somata in the NH and the external zone of the ME, these regions do not need an EC barrier to protect neurons and, hence, their capillaries possess fenestrated features.…”

Section: Size-limited Vascular Permeabilitymentioning

confidence: 99%

“…Blood-derived low-molecular-weight (LMW) molecules have been detected at the interstitial space after the administration of LMW tracers such as neutral amino acid alpha-aminoisobutyric acid [MW = 103 ( 27 )], fluorescein isothiocyanate [FITC; MM = 390 ( 23 , 28 )], Evans blue [MM = 961 ( 28 )], and Dextran 3,000 [MW = 3,000 ( 23 )] in the NH; fluorescein [MM = 332 ( 29 )], FITC ( 28 , 30 , 31 ), and Dextran 3,000 ( 31 ) in the external zone of the ME. The molecular weights of these tracers mimic those of most hypothalamic neuropeptides.…”

Section: Size-limited Vascular Permeabilitymentioning

confidence: 99%

“…The molecular weights of these tracers mimic those of most hypothalamic neuropeptides. In contrast to LMW molecules, blood-derived high-molecular-weight (HMW) molecules were not detected at the interstitial space after the administration of tracers, such as bovine serum albumin [MW = 70,000 ( 28 )], Dextran 10,000 [MM = 10,000 ( 23 )], and Dextran 70,000 [MM = 70,000 ( 28 )] in the NH; immunoglobulin [MW = 150,000 ( 29 )], bovine serum albumin [MW = 70,000 ( 28 )], Dextran 10,000 [MW = 10,000 ( 31 )], and Dextran 70,000 [MW = 70,000 ( 28 )] at the interstitial space in the external zone of the ME.…”

Section: Size-limited Vascular Permeabilitymentioning

confidence: 99%

See 2 more Smart Citations

Advances in Understanding of Structural Reorganization in the Hypothalamic Neurosecretory System

Miyata

2017

Front. Endocrinol.

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The hypothalamic neurosecretory system synthesizes neuropeptides in hypothalamic nuclei and releases them from axonal terminals into the circulation in the neurohypophysis (NH) and median eminence (ME). This system plays a crucial role in regulating body fluid homeostasis and social behaviors as well as reproduction, growth, metabolism, and stress responses, and activity-dependent structural reorganization has been reported. Current knowledge on dynamic structural reorganization in the NH and ME, in which the axonal terminals of neurosecretory neurons directly contact the basement membrane (BM) of a fenestrated vasculature, is discussed herein. Glial cells, pituicytes in the NH and tanycytes in the ME, engulf axonal terminals and interpose their cellular processes between axonal terminals and the BM when hormonal demands are low. Increasing demands for neurosecretion result in the retraction of the cellular processes of glial cells from axonal terminals and the BM, permitting increased neurovascular contact. The shape conversion of pituicytes and tanycytes is mediated by neurotransmitters and sex steroid hormones, respectively. The NH and ME have a rough vascular BM profile of wide perivascular spaces and specialized extension structures called "perivascular protrusions." Perivascular protrusions, the insides of which are occupied by the cellular processes of vascular mural cells pericytes, contribute to increasing neurovascular contact and, thus, the efficient diffusion of hypothalamic neuropeptides. A chronic physiological stimulation has been shown to increase perivascular protrusions via the shape conversion of pericytes and the profile of the vascular surface. Continuous angiogenesis occurs in the NH and ME of healthy normal adult rodents depending on the signaling of vascular endothelial growth factor (VEGF). The inhibition of VEGF signaling suppresses the proliferation of endothelial cells (ECs) and promotes their apoptosis, which results in decreases in the population of ECs and axonal terminals. Pituicytes and tanycytes are continuously replaced by the proliferation and differentiation of stem/progenitor cells, which may be regulated by matching those of ECs and axonal terminals. In conclusion, structural reorganization in the NH and ME is caused by the activity-dependent shape conversion of glial cells and vascular mural cells as well as the proliferation of endothelial and glial cells by angiogenesis and gliogenesis, respectively.

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Transient increase of microglial C1q expression in the circumventricular organs of adult mouse during LPS‐induced inflammation

Kawai

Kurganov

Miyata

2020

Cell Biochemistry & Function

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The circumventricular organs (CVOs) are the brain regions that lack the blood-brain barrier and allow free entry of blood-derived molecules, offering specialized niche to initiate rapid and early neuroinflammatory responses in the brain. Complement component 1q (C1q) is shown to be the first recognition component of the complement pathway and has a crucial function in the brain under pathological conditions. In the present study, we found that C1q expression in CX3CR1-positive microglia was increased in the CVOs and their neighbouring brain regions of adult mice at 1 day after a single administration of 1 mg/kg lipopolysaccharide (LPS), whereas it returned to control levels at 3 days after LPS stimulation. C1q expression was also seen to localize at synapsin-positive presynaptic axonal terminals in various brain regions. Thus, the present study demonstrates a transient upregulation of microglial C1q expression in the CVOs and their adjacent brain regions, indicating that a transient upregulation of C1q is possibly concerned with physiological responses at early phase of brain inflammation.Significance of the Study: The circumventricular organs (CVOs) are specialized brain regions that lack the blood-brain barrier (BBB) and initiate neuroinflammatory responses in the brains. The present study showed that the expression of complement protein C1q was highly increased in microglia of the CVOs and their adjacent brain regions. Moreover, C1q expression was observed to localize specifically at presynaptic axonal terminals in the CVOs and their neighbouring brain regions. Thus, the present study indicates that C1q is possibly correlated with physiological responses at early phase of brain inflammation. K E Y W O R D Sbrain, complement pathway, immunohistochemistry, inflammation, microglia

show abstract

Structural Reconstruction of the Perivascular Space in the Adult Mouse Neurohypophysis During an Osmotic Stimulation

Cited by 10 publications

References 69 publications

Single-Cell Molecular and Cellular Architecture of the Mouse Neurohypophysis

Single-Cell Molecular and Cellular Architecture of the Mouse Neurohypophysis

Advances in Understanding of Structural Reorganization in the Hypothalamic Neurosecretory System

Transient increase of microglial C1q expression in the circumventricular organs of adult mouse during LPS‐induced inflammation

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