Systemic angiotensin II and exercise-induced neurogenesis in adult rat hippocampus

Mukuda, Takao; Koyama, Yuka; Hamasaki, Sawako; Kaidoh, Toshiyuki; Furukawa, Yasuo

doi:10.1016/j.brainres.2014.09.019

Cited by 13 publications

(18 citation statements)

References 69 publications

(107 reference statements)

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Recent studies have shown that physical exercise stimulates levels of circulating Ang II in rats [40,41]. A pro-mitotic effect was also observed following intravascular Ang II infusion into rats, which was reversed by AT1 blockade with losartan [41]. Our data show that AT1 activation is required for running-induced proliferation.…”

Section: Discussionsupporting

confidence: 64%

“…Manipulation of angiotensin peptide levels during running might impact cell proliferation in the DG. Recent studies have shown that physical exercise stimulates levels of circulating Ang II in rats [40,41]. A pro-mitotic effect was also observed following intravascular Ang II infusion into rats, which was reversed by AT1 blockade with losartan [41].…”

Section: Discussionmentioning

confidence: 98%

See 1 more Smart Citation

Depletion of angiotensin-converting enzyme 2 reduces brain serotonin and impairs the running-induced neurogenic response

Klempin

Mosienko

Matthes

et al. 2018

Cell. Mol. Life Sci.

View full text Add to dashboard Cite

Physical exercise induces cell proliferation in the adult hippocampus in rodents. Serotonin (5-HT) and angiotensin (Ang) II are important mediators of the pro-mitotic effect of physical activity. Here, we examine precursor cells in the adult brain of mice lacking angiotensin-converting enzyme (ACE) 2, and explore the effect of an acute running stimulus on neurogenesis. ACE2 metabolizes Ang II to Ang-(1-7) and is essential for the intestinal uptake of tryptophan (Trp), the 5-HT precursor. In ACE2-deficient mice, we observed a decrease in brain 5-HT levels and no increase in the number of BrdU-positive cells following exercise. Targeting the Ang II/AT1 axis by blocking the receptor, or experimentally increasing Trp/5-HT levels in the brain of ACE2-deficient mice, did not rescue the running-induced effect. Furthermore, mice lacking the Ang-(1-7) receptor, Mas, presented a normal neurogenic response to exercise. Our results identify ACE2 as a novel factor required for exercise-dependent modulation of adult neurogenesis and essential for 5-HT metabolism.

show abstract

Section: Discussionsupporting

confidence: 64%

Section: Discussionmentioning

confidence: 98%

Depletion of angiotensin-converting enzyme 2 reduces brain serotonin and impairs the running-induced neurogenic response

Klempin

Mosienko

Matthes

et al. 2018

Cell. Mol. Life Sci.

View full text Add to dashboard Cite

show abstract

“…Ghrelin was reported to regulate the synapse density of the HIP (Diano et al, ) and to stimulate adult neurogenesis directly (Li et al, ). Also, our recent study showed that blood‐borne Ang II stimulated the HIP, thereby enhancing neurogenesis in physiologically normal adult rats (Koyama et al, ; Mukuda et al, ). Although the penetration of blood‐derived signal molecules into the HIP is plausible, their direct access to hippocampal neurons has not been demonstrated.…”

Section: Discussionmentioning

confidence: 96%

“…With the progression of experimental research using model animals, the HIP has been suggested to be susceptible to blood‐borne molecules, such as Ang II and ghrelin, which enhanced hippocampal neurogenesis through the direct activation of hippocampal cells (Koyama et al, ; Li et al, ; Mukuda et al, ). However, the access routes of hormones have not been fully determined.…”

Section: Discussionmentioning

confidence: 99%

“…This peptide regulates the synapse density of the HIP (Diano et al, 2006) and stimulates adult neurogenesis directly (Li et al, 2013). Recently, we found that a transient increase in plasma Ang II levels triggered enhanced neurogenesis in the adult rat HIP, probably through trophic factor production in hippocampal astrocytes on which the peptide acts directly (Koyama, Mukuda, Hamasaki, Nakane, & Kaidoh, 2018;Mukuda, Koyama, Hamasaki, Kaidoh, & Furukawa, 2014). However, direct evidence that bloodborne products can access hippocampal neurons constitutively has not been reported.…”

Section: Introductionmentioning

confidence: 99%

See 1 more Smart Citation

Constitutive accessibility of circulating proteins to hippocampal neurons in physiologically normal rats

et al. 2020

Self Cite

View full text Add to dashboard Cite

Introduction Although the hippocampus (HIP) is thought impermeable to blood‐borne proteins because of the integrity of the blood–brain barrier (BBB), it was recently suggested to be susceptible to hydrophilic hormones. The present study determined the accessibility of blood‐borne signal molecules such as hormones to hippocampal neurons in physiologically normal rats. Methods As a probe for accessibility, Evans blue dye (EB) that rapidly binds to albumin (Alb), which is impermeable to the BBB, was injected intravenously. To increase the vascular permeability of the BBB, a daily single administration of angiotensin II (Ang II) was applied intravenously for seven consecutive days. Results Fifteen minutes after the injection of EB, histological observation revealed that a number of neurons had entrapped and accumulated EB into their cell bodies in the hippocampal dentate gyrus in all rats. Of these, relatively large oval neurons (>15 µm) in the hilus and molecular layer showed parvalbumin immunopositivity, indicating they are GABAergic interneurons. The population of EB‐accumulating neurons (approximately 10 µm) were localized in the inner margin of the granule cell layer, suggesting they were granule cells. However, the number of EB‐positive neurons did not change in rats treated with Ang II compared with vehicle injection. Conclusions These findings suggest an intriguing possibility that blood‐derived proteins such as hormones have access to hippocampal neurons constitutively in the absence of stimuli that increase the vascular permeability of the BBB in a physiologically normal state.

show abstract

Dopamine Regulates Adult Neurogenesis in the Ventricular-Subventricular Zone via Dopamine D3 Angiotensin Type 2 Receptor Interactions

et al. 2021

View full text Add to dashboard Cite

Adult neurogenesis is a dynamic and highly regulated process, and different studies suggest that dopamine modulates ventricular-subventricular zone (V-SVZ) neurogenesis. However, the specific role of dopamine and the mechanisms/factors underlying its effects on physiological and pathological conditions such as Parkinson's disease (PD) are not fully understood. Recent studies have described counter-regulatory interactions between renin-angiotensin system (RAS) and dopamine in peripheral tissues and in the nigrostriatal system. We have previously demonstrated that angiotensin receptors regulate proliferation and generation of neuroblasts in the rodent V-SVZ. However, possible interactions between dopamine receptors and RAS in the V-SVZ and their role in alterations of neurogenesis in animal models of PD have not been investigated. In V-SVZ cultures, activation of dopamine receptors induced changes in the expression of angiotensin receptors. Moreover, dopamine, via D2-like receptors and particularly D3 receptors, increased generation of neurospheres derived from the V-SVZ and this effect was mediated by angiotensin type-2 (AT2) receptors. In rats, we observed a marked reduction in proliferation and generation of neuroblasts in the V-SVZ of dopamine-depleted animals, and inhibition of AT1 receptors or activation of AT2 receptors restored proliferation and generation of neuroblasts to control levels. Moreover, intrastriatal mesencephalic grafts partially restored proliferation and generation of neuroblasts observed in the V-SVZ of dopamine-depleted rats. Our data revealed that dopamine and angiotensin receptor interactions play a major role in the regulation of V-SVZ and suggest potential beneficial effects of RAS modulators on the regulation of adult V-SVZ neurogenesis.

show abstract

Systemic angiotensin II and exercise-induced neurogenesis in adult rat hippocampus

Cited by 13 publications

References 69 publications

Depletion of angiotensin-converting enzyme 2 reduces brain serotonin and impairs the running-induced neurogenic response

Depletion of angiotensin-converting enzyme 2 reduces brain serotonin and impairs the running-induced neurogenic response

Constitutive accessibility of circulating proteins to hippocampal neurons in physiologically normal rats

Dopamine Regulates Adult Neurogenesis in the Ventricular-Subventricular Zone via Dopamine D3 Angiotensin Type 2 Receptor Interactions

Contact Info

Product

Resources

About