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Article

Losartan Improves Memory, Neurogenesis and Cell Motility in Transgenic Alzheimer’s Mice

1
Department of Clinical Pharmacology, University Hospital of Tuebingen, 72076 Tuebingen, Germany
2
Dr. Margarete Fischer-Bosch-Institute of Clinical Pharmacology, 70376 Stuttgart, Germany
3
H. Buniatian Institute of Biochemistry, National Academy of Sciences of the Republic of Armenia (NASRA), Yerevan 0019, Armenia
4
HealthPartners Center for Memory and Aging, HealthPartners Neurosciences, St. Paul, MN 55130, USA
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CytoSMART, 5611 AZ Eindhoven, The Netherlands
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Department of Biochemistry and Neuroscience Laboratory, Yerevan State Medical University, Yerevan 0025, Armenia
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Department of Biochemistry and Pharmacy, University of Tuebingen, 72074 Tuebingen, Germany
8
Department of Clinical Pharmacology, Yerevan State Medical University, Yerevan 0025, Armenia
*
Author to whom correspondence should be addressed.
Academic Editor: Thierry Besson
Pharmaceuticals 2021, 14(2), 166; https://doi.org/10.3390/ph14020166
Received: 22 January 2021 / Revised: 16 February 2021 / Accepted: 18 February 2021 / Published: 20 February 2021
(This article belongs to the Special Issue New Drugs and Biologics For Treatment of Central Nervous Dysfunction)
Angiotensin receptor blockers (ARBs) have demonstrated multiple neuroprotective benefits in Alzheimer’s disease (AD) models. However, their beneficial effects on memory deficits, cholinergic activity, neurogenesis and Amyloid beta (Aβ) clearance reveal significant interstudy variability. The delivery route can impact not only delivery but also targeting and therapeutic efficacy of ARBs. Our previous findings on the beneficial effects of intranasally delivered losartan in the APP/PS1 model of AD prompted us to explore the influence of the delivery route by employing here the systemic administration of losartan. Consistent with our previous results with intranasal losartan, repeated intraperitoneal administration (10 mg/kg) resulted in a remarkable decrease in Aβ plaques and soluble Aβ42, as well as inflammatory cytokines (IL-2, IL-6 and TNFα). The Aβ reduction can be ascribed to its facilitated degradation by neprilysin and diminished generation by BACE1. Losartan increased neurogenesis in vivo and in vitro and improved migratory properties of astrocytes isolated from adult transgenic AD mice. In summary, this data together with our previous results suggest therapeutic features of losartan which are independent of delivery route. The improvement of cell motility of Aβ-affected astrocytes by losartan deserves further in vivo investigation, which may lead to new strategies for AD treatment. View Full-Text
Keywords: angiotensin receptor; amyloid beta; neuroinflammation; cell migration; cell motility; neprilysin; BACE1; 3xTg-AD; APP/PS1; cholinergic angiotensin receptor; amyloid beta; neuroinflammation; cell migration; cell motility; neprilysin; BACE1; 3xTg-AD; APP/PS1; cholinergic
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MDPI and ACS Style

Drews, H.J.; Klein, R.; Lourhmati, A.; Buadze, M.; Schaeffeler, E.; Lang, T.; Seferyan, T.; Hanson, L.R.; Frey II, W.H.; de Vries, T.C.G.M.; Thijssen-van Loosdregt, I.A.E.W.; Gleiter, C.H.; Schwab, M.; Danielyan, L. Losartan Improves Memory, Neurogenesis and Cell Motility in Transgenic Alzheimer’s Mice. Pharmaceuticals 2021, 14, 166. https://doi.org/10.3390/ph14020166

AMA Style

Drews HJ, Klein R, Lourhmati A, Buadze M, Schaeffeler E, Lang T, Seferyan T, Hanson LR, Frey II WH, de Vries TCGM, Thijssen-van Loosdregt IAEW, Gleiter CH, Schwab M, Danielyan L. Losartan Improves Memory, Neurogenesis and Cell Motility in Transgenic Alzheimer’s Mice. Pharmaceuticals. 2021; 14(2):166. https://doi.org/10.3390/ph14020166

Chicago/Turabian Style

Drews, Henning J., Roman Klein, Ali Lourhmati, Marine Buadze, Elke Schaeffeler, Thomas Lang, Torgom Seferyan, Leah R. Hanson, William H. Frey II, Tom C.G.M. de Vries, Inge A.E.W. Thijssen-van Loosdregt, Christoph H. Gleiter, Matthias Schwab, and Lusine Danielyan. 2021. "Losartan Improves Memory, Neurogenesis and Cell Motility in Transgenic Alzheimer’s Mice" Pharmaceuticals 14, no. 2: 166. https://doi.org/10.3390/ph14020166

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