PMID- 36939204
OWN - NLM
STAT- MEDLINE
DCOM- 20230503
LR  - 20240502
IS  - 1531-2267 (Electronic)
IS  - 1094-8341 (Print)
IS  - 1094-8341 (Linking)
VI  - 55
IP  - 5
DP  - 2023 May 1
TI  - Impact of exercise on brain-bone marrow interactions in chronic stress: potential 
      mechanisms preventing stress-induced hypertension.
PG  - 222-234
LID - 10.1152/physiolgenomics.00168.2022 [doi]
AB  - We examined the effect of chronic restraint stress and the counteractive effects 
      of daily exercise on the molecular basis of the brain-bone marrow (BM) 
      interactions, by especially focusing on the paraventricular nucleus (PVN) of the 
      hypothalamus. Male Wistar rats were assigned into control, restraint stress, and 
      stress + daily spontaneous exercise (SE) groups. BM and hypothalamic gene 
      expression profiles were examined through the undertaking of RT-PCR and 
      microarrays, respectively. The inflammatory blood cell population was 
      investigated through flow cytometry. Through the use of immunohistochemistry, we 
      examined the presence of BM-derived C-C chemokine receptor type 2 
      (CCR2)-expressing microglial cells in the rat PVN. The gene expression levels of 
      BM inflammatory factors such as those of interleukin 1 beta and CCR2, and the 
      inflammatory blood cell population were found to be significantly higher in both 
      restrained groups compared with control group. Interestingly, chronic restraint 
      stress alone activated the recruitment of BM-derived CCR2-expressing microglial 
      cells into the PVN, whereas daily spontaneous exercise prevented it. A notable 
      finding was that restraint stress upregulated relative gene expression of 
      hypothalamic matrix metalloproteinase 3 (MMP3), which increases the permeability 
      of the blood-brain barrier (BBB), and that exercise managed to normalize it. 
      Moreover, relative expression of some hypothalamic genes directly involved in the 
      facilitation of cell migration was downregulated by daily exercise. Our findings 
      suggest that daily spontaneous exercise can reduce the numbers of BM-derived 
      CCR2-expressing microglial cells into the PVN through the prevention of 
      stress-induced changes in the hypothalamic gene expression.NEW & NOTEWORTHY 
      Chronic restraint stress can upregulate MMP3 gene expression in the rat 
      hypothalamus, whereas daily spontaneous exercise can prevent this stress-induced 
      effect. Stress-induced BM-derived inflammatory cell recruitment into the rat PVN 
      can be prevented by daily spontaneous exercise. Stress-induced increase of 
      hypothalamic MMP3 gene expression may be responsible for BBB injury, thereby 
      allowing for BM-derived inflammatory cells to be recruited and to accumulate in 
      the rat PVN, and to be subsequently involved in the onset of stress-induced 
      hypertension.
FAU - Nguyen, Thu Van
AU  - Nguyen TV
AUID- ORCID: 0000-0002-8390-4560
AD  - Department of Physiology, Graduate School of Health and Sports Science, Juntendo 
      University, Chiba, Japan.
AD  - Department of Military Occupational Medicine, Vietnam Military Medical 
      University, Hanoi, Vietnam.
FAU - Yamanaka, Ko
AU  - Yamanaka K
AD  - Department of Physiology, Graduate School of Health and Sports Science, Juntendo 
      University, Chiba, Japan.
FAU - Tomita, Keisuke
AU  - Tomita K
AD  - Department of Physiology, Graduate School of Health and Sports Science, Juntendo 
      University, Chiba, Japan.
FAU - Zubcevic, Jasenka
AU  - Zubcevic J
AUID- ORCID: 0000-0003-3840-3211
AD  - Department of Physiology and Pharmacology, University of Toledo, Toledo, Ohio, 
      United States.
FAU - Gouraud, Sabine S S
AU  - Gouraud SSS
AUID- ORCID: 0000-0002-4917-0647
AD  - College of Liberal Arts, International Christian University, Tokyo, Japan.
FAU - Waki, Hidefumi
AU  - Waki H
AUID- ORCID: 0000-0002-4278-2077
AD  - Department of Physiology, Graduate School of Health and Sports Science, Juntendo 
      University, Chiba, Japan.
LA  - eng
SI  - figshare/10.6084/m9.figshare.21716627
GR  - R01 HL152162/HL/NHLBI NIH HHS/United States
PT  - Journal Article
PT  - Research Support, N.I.H., Extramural
PT  - Research Support, Non-U.S. Gov't
DEP - 20230320
PL  - United States
TA  - Physiol Genomics
JT  - Physiological genomics
JID - 9815683
RN  - EC 3.4.24.17 (Matrix Metalloproteinase 3)
SB  - IM
MH  - Rats
MH  - Male
MH  - Animals
MH  - *Matrix Metalloproteinase 3
MH  - Rats, Wistar
MH  - Bone Marrow
MH  - *Hypertension
MH  - Brain
PMC - PMC10151049
OTO - NOTNLM
OT  - CCR2
OT  - MMP3
OT  - brain-bone marrow interaction
OT  - exercise
OT  - stress-induced hypertension
COIS- No conflicts of interest, financial or otherwise, are declared by the authors.
EDAT- 2023/03/21 06:00
MHDA- 2023/05/03 06:42
PMCR- 2024/05/01
CRDT- 2023/03/20 08:43
PHST- 2023/05/03 06:42 [medline]
PHST- 2023/03/21 06:00 [pubmed]
PHST- 2023/03/20 08:43 [entrez]
PHST- 2024/05/01 00:00 [pmc-release]
AID - PG-00168-2022 [pii]
AID - 10.1152/physiolgenomics.00168.2022 [doi]
PST - ppublish
SO  - Physiol Genomics. 2023 May 1;55(5):222-234. doi: 
      10.1152/physiolgenomics.00168.2022. Epub 2023 Mar 20.