Antidepressant-induced vascular dynamics in the hippocampus of adult mouse brain

Mannari, Tetsuya; Sawa, Hayato; Furube, Eriko; Fukushima, Shohei; Nishikawa, Kazunori; Nakashimna, Toshihiro; Miyata, Seiji

doi:10.1007/s00441-014-1933-6

Cited by 11 publications

(4 citation statements)

References 72 publications

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“…13,14 In brief, cultured cells plated on poly-d-lysine-coated coverslips were fixed with 4% paraformaldehyde in 0.1 M phosphate-buffered saline (PBS) (pH 7.4) for 10 minutes. After permeabilization with 0.3% Triton X-100 in PBS (PBST), cells were blocked with 5% normal horse serum in PBST and incubated with Alexa Fluor-546-conjugated phalloidin and the following primary antibodies: mouse anti-collagen I (1:100, Abcam), rabbit anti-collagen IV (1:100, Progen), guinea pig anti-laminin (1:200, gift from Dr. Miyata), 22 mouse anti-Tuj1 (1:200, Covance), or rabbit anti-glial fibrillary acidic protein (GFAP; 1:1000, Abcam). They were further incubated with species-specific secondary antibodies conjugated with Alexa Fluor-488 (1:1000, Thermo Fisher) or CF-555 (1:1000, Biotium).…”

Section: Immunostainingmentioning

confidence: 99%

Bone marrow stromal cell sheets may promote axonal regeneration and functional recovery with suppression of glial scar formation after spinal cord transection injury in rats

Okuda

Horii-Hayashi

Sasagawa

et al. 2017

SPI

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OBJECTIVE Transplantation of bone marrow stromal cells (BMSCs) is a theoretical potential as a therapeutic strategy in the treatment of spinal cord injury (SCI). Although a scaffold is sometimes used for retaining transplanted cells in damaged tissue, it is also known to induce redundant immunoreactions during the degradation processes. In this study, the authors prepared cell sheets made of BMSCs, which are transplantable without a scaffold, and investigated their effects on axonal regeneration, glial scar formation, and functional recovery in a completely transected SCI model in rats. METHODS BMSC sheets were prepared from the bone marrow of female Fischer 344 rats using ascorbic acid and were cryopreserved until the day of transplantation. A gelatin sponge (GS), as a control, or BMSC sheet was transplanted into a 2-mm-sized defect of the spinal cord at the T-8 level. Axonal regeneration and glial scar formation were assessed 2 and 8 weeks after transplantation by immunohistochemical analyses using anti-Tuj1 and glial fibrillary acidic protein (GFAP) antibodies, respectively. Locomotor function was evaluated using the Basso, Beattie, and Bresnahan scale. RESULTS The BMSC sheets promoted axonal regeneration at 2 weeks after transplantation, but there was no significant difference in the number of Tuj1-positive axons between the sheet- and GS-transplanted groups. At 8 weeks after transplantation, Tuj1-positive axons elongated across the sheet, and their numbers were significantly greater in the sheet group than in the GS group. The areas of GFAP-positive glial scars in the sheet group were significantly reduced compared with those of the GS group at both time points. Finally, hindlimb locomotor function was ameliorated in the sheet group at 4 and 8 weeks after transplantation. CONCLUSIONS The results of the present study indicate that an ascorbic acid–induced BMSC sheet is effective in the treatment of SCI and enables autologous transplantation without requiring a scaffold.

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Section: Immunostainingmentioning

confidence: 99%

Bone marrow stromal cell sheets may promote axonal regeneration and functional recovery with suppression of glial scar formation after spinal cord transection injury in rats

Okuda

Horii-Hayashi

Sasagawa

et al. 2017

SPI

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“…The perivascular structures of the NH ( 47 – 50 ) and ME ( 51 ) largely differ from those generally observed in the brain because they have a wide perivascular space between the inner and outer BMs. Therefore, the profile of the outer BM or vascular surface in the NH [( 40 ); Figure 2 A] and ME [( 42 ); Figure 2 B] is more complex or uneven than that of the general BBB-containing brain vasculature [( 52 ); Figure 2 C]. This irregularity in the vascular surface is primarily due to the complex cellular processes of pericytes that function as vascular mural cells surrounding ECs [( 23 ); Figure 2 D].…”

Section: Significance Of the Perivascular Space In Neurosecretionmentioning

confidence: 99%

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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“…A previous study reported that the overexpression of VEGF-A significantly increased angiogenesis and neurogenesis in the adult hippocampus (Udo et al, 2008 ). Electroconvulsive seizures and antidepressants, which are proven therapeutics in the treatment of several depressive diseases, increased vascular density in the DG of adult rodents and humans (Newton et al, 2006 ; Mannari et al, 2014 ). NSCs have a perivascular niche that intimately associates with endothelial cells, possibly via VEGF and BDNF signaling, in the SGZ and SVZ of adult mammalian brains (Goldman and Chen, 2011 ).…”

Section: Angiogenesismentioning

confidence: 99%

New aspects in fenestrated capillary and tissue dynamics in the sensory circumventricular organs of adult brains

2015

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The blood–brain barrier (BBB) generally consists of endothelial tight junction barriers that prevent the free entry of blood-derived substances, thereby maintaining the extracellular environment of the brain. However, the circumventricular organs (CVOs), which are located along the midlines of the brain ventricles, lack these endothelial barriers and have fenestrated capillaries; therefore, they have a number of essential functions, including the transduction of information between the blood circulation and brain. Previous studies have demonstrated the extensive contribution of the CVOs to body fluid and thermal homeostasis, energy balance, the chemoreception of blood-derived substances, and neuroinflammation. In this review, recent advances have been discussed in fenestrated capillary characterization and dynamic tissue reconstruction accompanied by angiogenesis and neurogliogenesis in the sensory CVOs of adult brains. The sensory CVOs, including the organum vasculosum of the lamina terminalis (OVLT), subfornical organ (SFO), and area postrema (AP), have size-selective and heterogeneous vascular permeabilities. Astrocyte-/tanycyte-like neural stem cells (NSCs) sense blood- and cerebrospinal fluid-derived information through the transient receptor potential vanilloid 1, a mechanical/osmotic receptor, Toll-like receptor 4, a lipopolysaccharide receptor, and Nax, a Na-sensing Na channel. They also express tight junction proteins and densely and tightly surround mature neurons to protect them from blood-derived neurotoxic substances, indicating that the NSCs of the CVOs perform BBB functions while maintaining the capacity to differentiate into new neurons and glial cells. In addition to neurogliogenesis, the density of fenestrated capillaries is regulated by angiogenesis, which is accompanied by the active proliferation and sprouting of endothelial cells. Vascular endothelial growth factor (VEGF) signaling may be involved in angiogenesis and neurogliogenesis, both of which affect vascular permeability. Thus, recent findings advocate novel concepts for the CVOs, which have the dynamic features of vascular and parenchymal tissues.

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Antidepressant-induced vascular dynamics in the hippocampus of adult mouse brain

Cited by 11 publications

References 72 publications

Bone marrow stromal cell sheets may promote axonal regeneration and functional recovery with suppression of glial scar formation after spinal cord transection injury in rats

Bone marrow stromal cell sheets may promote axonal regeneration and functional recovery with suppression of glial scar formation after spinal cord transection injury in rats

Advances in Understanding of Structural Reorganization in the Hypothalamic Neurosecretory System

New aspects in fenestrated capillary and tissue dynamics in the sensory circumventricular organs of adult brains

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