Aging exacerbates impairments of cerebral blood flow autoregulation and cognition in diabetic rats

Diabetes mellitus (DM) is a leading risk factor for aging-related dementia; however, the underlying mechanisms are not well understood. The present study, utilizing a non-obese T2DN diabetic model, demonstrates that the myogenic response of the middle cerebral artery (MCA) and parenchymal arteriole...

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Published in:GeroScience Vol. 42; no. 5; pp. 1387 - 1410
Main Authors: Wang, Shaoxun, Lv, Wenshan, Zhang, Huawei, Liu, Yedan, Li, Longyang, Jefferson, Joshua R., Guo, Ya, Li, Man, Gao, Wenjun, Fang, Xing, Paul, Ian A., Rajkowska, Grazyna, Shaffery, James P., Mosley, Thomas H., Hu, Xinlin, Liu, Ruen, Wang, Yangang, Yu, Hongwei, Roman, Richard J., Fan, Fan
Format: Journal Article
Language:English
Published: Cham Springer International Publishing 01.10.2020
Springer Nature B.V
Subjects:
Aging
Animals
Antidiabetics
Biomedical and Life Sciences
Blood flow
Blood-brain barrier
Brain
Capillaries
Cell Biology
Cerebral blood flow
Cerebrovascular Circulation
Cognition
Cortex
Dementia
Dementia disorders
Diabetes
Diabetes mellitus
Diabetes Mellitus, Experimental - complications
Geriatrics
Geriatrics/Gerontology
Hippocampus
Homeostasis
Hyperemia
Life Sciences
Long term memory
Memory
Molecular Medicine
Neurodegeneration
Obesity
Older people
Original
Original Article
Perfusion
Rats
Risk factors
Rodents
Short term memory
Spatial discrimination learning
Spatial memory
Autoregulation
Cognitive impairments
Myogenic response
Blood-brain barrier
Diabetes mellitus
ISSN:2509-2715, 2509-2723, 2509-2723
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Abstract Diabetes mellitus (DM) is a leading risk factor for aging-related dementia; however, the underlying mechanisms are not well understood. The present study, utilizing a non-obese T2DN diabetic model, demonstrates that the myogenic response of the middle cerebral artery (MCA) and parenchymal arteriole (PA) and autoregulation of cerebral blood flow (CBF) in the surface and deep cortex were impaired at both young and old ages. The impaired CBF autoregulation was more severe in old than young DM rats, and in the deep than the surface cortex. The myogenic tone of the MCA was enhanced at perfusion pressure in the range of 40–100 mmHg in young DM rats but was reduced at 140–180 mmHg in old DM rats. No change of the myogenic tone of the PA was observed in young DM rats, whereas it was significantly reduced at 30–60 mmHg in old DM rats. Old DM rats had enhanced blood-brain barrier (BBB) leakage and neurodegeneration, reduced vascular density, tight junction, and pericyte coverage on cerebral capillaries in the CA3 region in the hippocampus. Additionally, DM rats displayed impaired functional hyperemia and spatial learning and short- and long-term memory at both young and old ages. Old DM rats had impaired non-spatial short-term memory. These results revealed that impaired CBF autoregulation and enhanced BBB leakage plays an essential role in the pathogenesis of age- and diabetes-related dementia. These findings will lay the foundations for the discovery of anti-diabetic therapies targeting restoring CBF autoregulation to prevent the onset and progression of dementia in elderly DM.
AbstractList Diabetes mellitus (DM) is a leading risk factor for aging-related dementia; however, the underlying mechanisms are not well understood. The present study, utilizing a non-obese T2DN diabetic model, demonstrates that the myogenic response of the middle cerebral artery (MCA) and parenchymal arteriole (PA) and autoregulation of cerebral blood flow (CBF) in the surface and deep cortex were impaired at both young and old ages. The impaired CBF autoregulation was more severe in old than young DM rats, and in the deep than the surface cortex. The myogenic tone of the MCA was enhanced at perfusion pressure in the range of 40-100 mmHg in young DM rats but was reduced at 140-180 mmHg in old DM rats. No change of the myogenic tone of the PA was observed in young DM rats, whereas it was significantly reduced at 30-60 mmHg in old DM rats. Old DM rats had enhanced blood-brain barrier (BBB) leakage and neurodegeneration, reduced vascular density, tight junction, and pericyte coverage on cerebral capillaries in the CA3 region in the hippocampus. Additionally, DM rats displayed impaired functional hyperemia and spatial learning and short- and long-term memory at both young and old ages. Old DM rats had impaired non-spatial short-term memory. These results revealed that impaired CBF autoregulation and enhanced BBB leakage plays an essential role in the pathogenesis of age- and diabetes-related dementia. These findings will lay the foundations for the discovery of anti-diabetic therapies targeting restoring CBF autoregulation to prevent the onset and progression of dementia in elderly DM.
Diabetes mellitus (DM) is a leading risk factor for aging-related dementia; however, the underlying mechanisms are not well understood. The present study, utilizing a non-obese T2DN diabetic model, demonstrates that the myogenic response of the middle cerebral artery (MCA) and parenchymal arteriole (PA) and autoregulation of cerebral blood flow (CBF) in the surface and deep cortex were impaired at both young and old ages. The impaired CBF autoregulation was more severe in old than young DM rats, and in the deep than the surface cortex. The myogenic tone of the MCA was enhanced at perfusion pressure in the range of 40–100 mmHg in young DM rats but was reduced at 140–180 mmHg in old DM rats. No change of the myogenic tone of the PA was observed in young DM rats, whereas it was significantly reduced at 30–60 mmHg in old DM rats. Old DM rats had enhanced blood-brain barrier (BBB) leakage and neurodegeneration, reduced vascular density, tight junction, and pericyte coverage on cerebral capillaries in the CA3 region in the hippocampus. Additionally, DM rats displayed impaired functional hyperemia and spatial learning and short- and long-term memory at both young and old ages. Old DM rats had impaired non-spatial short-term memory. These results revealed that impaired CBF autoregulation and enhanced BBB leakage plays an essential role in the pathogenesis of age- and diabetes-related dementia. These findings will lay the foundations for the discovery of anti-diabetic therapies targeting restoring CBF autoregulation to prevent the onset and progression of dementia in elderly DM.
Diabetes mellitus (DM) is a leading risk factor for aging-related dementia; however, the underlying mechanisms are not well understood. The present study, utilizing a non-obese T2DN diabetic model, demonstrates that the myogenic response of the middle cerebral artery (MCA) and parenchymal arteriole (PA) and autoregulation of cerebral blood flow (CBF) in the surface and deep cortex were impaired at both young and old ages. The impaired CBF autoregulation was more severe in old than young DM rats, and in the deep than the surface cortex. The myogenic tone of the MCA was enhanced at perfusion pressure in the range of 40-100 mmHg in young DM rats but was reduced at 140-180 mmHg in old DM rats. No change of the myogenic tone of the PA was observed in young DM rats, whereas it was significantly reduced at 30-60 mmHg in old DM rats. Old DM rats had enhanced blood-brain barrier (BBB) leakage and neurodegeneration, reduced vascular density, tight junction, and pericyte coverage on cerebral capillaries in the CA3 region in the hippocampus. Additionally, DM rats displayed impaired functional hyperemia and spatial learning and short- and long-term memory at both young and old ages. Old DM rats had impaired non-spatial short-term memory. These results revealed that impaired CBF autoregulation and enhanced BBB leakage plays an essential role in the pathogenesis of age- and diabetes-related dementia. These findings will lay the foundations for the discovery of anti-diabetic therapies targeting restoring CBF autoregulation to prevent the onset and progression of dementia in elderly DM.Diabetes mellitus (DM) is a leading risk factor for aging-related dementia; however, the underlying mechanisms are not well understood. The present study, utilizing a non-obese T2DN diabetic model, demonstrates that the myogenic response of the middle cerebral artery (MCA) and parenchymal arteriole (PA) and autoregulation of cerebral blood flow (CBF) in the surface and deep cortex were impaired at both young and old ages. The impaired CBF autoregulation was more severe in old than young DM rats, and in the deep than the surface cortex. The myogenic tone of the MCA was enhanced at perfusion pressure in the range of 40-100 mmHg in young DM rats but was reduced at 140-180 mmHg in old DM rats. No change of the myogenic tone of the PA was observed in young DM rats, whereas it was significantly reduced at 30-60 mmHg in old DM rats. Old DM rats had enhanced blood-brain barrier (BBB) leakage and neurodegeneration, reduced vascular density, tight junction, and pericyte coverage on cerebral capillaries in the CA3 region in the hippocampus. Additionally, DM rats displayed impaired functional hyperemia and spatial learning and short- and long-term memory at both young and old ages. Old DM rats had impaired non-spatial short-term memory. These results revealed that impaired CBF autoregulation and enhanced BBB leakage plays an essential role in the pathogenesis of age- and diabetes-related dementia. These findings will lay the foundations for the discovery of anti-diabetic therapies targeting restoring CBF autoregulation to prevent the onset and progression of dementia in elderly DM.
Author Paul, Ian A.
Shaffery, James P.
Roman, Richard J.
Lv, Wenshan
Li, Man
Gao, Wenjun
Wang, Shaoxun
Guo, Ya
Yu, Hongwei
Liu, Yedan
Li, Longyang
Mosley, Thomas H.
Fan, Fan
Fang, Xing
Zhang, Huawei
Jefferson, Joshua R.
Hu, Xinlin
Rajkowska, Grazyna
Liu, Ruen
Wang, Yangang
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  organization: Department of Pharmacology and Toxicology, University of Mississippi Medical Center
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  organization: Department of Pharmacology and Toxicology, University of Mississippi Medical Center
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  organization: Department of Pharmacology and Toxicology, University of Mississippi Medical Center
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  organization: Department of Psychiatry and Human Behavior, University of Mississippi Medical Center
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  organization: Department of Pharmacology and Toxicology, University of Mississippi Medical Center
BackLink https://www.ncbi.nlm.nih.gov/pubmed/32696219$$D View this record in MEDLINE/PubMed
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Keywords Autoregulation
Cognitive impairments
Myogenic response
Blood-brain barrier
Diabetes mellitus
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Snippet Diabetes mellitus (DM) is a leading risk factor for aging-related dementia; however, the underlying mechanisms are not well understood. The present study,...
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StartPage 1387
SubjectTerms Aging
Animals
Antidiabetics
Biomedical and Life Sciences
Blood flow
Blood-brain barrier
Brain
Capillaries
Cell Biology
Cerebral blood flow
Cerebrovascular Circulation
Cognition
Cortex
Dementia
Dementia disorders
Diabetes
Diabetes mellitus
Diabetes Mellitus, Experimental - complications
Geriatrics
Geriatrics/Gerontology
Hippocampus
Homeostasis
Hyperemia
Life Sciences
Long term memory
Memory
Molecular Medicine
Neurodegeneration
Obesity
Older people
Original
Original Article
Perfusion
Rats
Risk factors
Rodents
Short term memory
Spatial discrimination learning
Spatial memory
Title Aging exacerbates impairments of cerebral blood flow autoregulation and cognition in diabetic rats
URI https://link.springer.com/article/10.1007/s11357-020-00233-w
https://www.ncbi.nlm.nih.gov/pubmed/32696219
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https://www.proquest.com/docview/2426175564
https://pubmed.ncbi.nlm.nih.gov/PMC7525432
Volume 42
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