Thrombin, a mediator of neurotoxicity and memory impairment

Mhatre, Molina; Nguyen, Albert; Kashani, Shabnam; Pham, Tracy; Adesina, Adekunle; Grammas, Paula

doi:10.1016/j.neurobiolaging.2003.07.007

Cited by 105Alzheimer's disease research and treatmentsNeurological Disease Mechanisms and TreatmentsBlood Coagulation and Thrombosis Mechanisms

Thrombin, a mediator of neurotoxicity and memory impairment

Mhatre, Molina, Nguyen, Albert, Kashani, Shabnam, Pham, Tracy, Adesina, Adekunle, Grammas, Paula·2004·Neurobiology of Aging

DOI 10.1016/j.neurobiolaging.2003.07.007

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Abstract

Thrombin has been found in neuritic plaques in Alzheimer's disease (AD). Also, traumatic brain injury, where neurons are exposed to high thrombin levels, is associated with an increased incidence of AD. Our objective was to determine the effects of thrombin administered in vivo on cognitive function and neuropathology. Rats were trained using a radial eight-arm maze and then thrombin (25 or 100 nM, 0.25 microl/h, 28 days) or vehicle was delivered via intracerebroventricular infusion. Animals that received 100 nM thrombin demonstrated cognitive impairments including deficits in reference memory and an increase in task latency. Also, significant neuropathology was detected in these animals such as enlargement of cerebral ventricles, an increased number of TUNEL-positive cells, astrogliosis, and an increase in the immunoreactivity for phosphorylated neurofilament, and apolipoprotein-E fragments. Thrombin-induced changes in cognitive function and ventricular enlargement were inhibited by hirudin. These findings demonstrate that thrombin is a mediator of neurotoxicity and cognitive deficits and suggest that inhibition of thrombin may be a treatment strategy for AD- or head trauma-associated cognitive deficits.

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Authors: Mhatre, M., Nguyen, A., Kashani, S., Pham, T., Adesina, A., & Grammas, P.
Affiliations: University of Oklahoma Health Sciences Center (US)
Corresponding author: Grammas, Paula
ORCID: Adesina, Adekunle
Grammas, Paula
Venue: Neurobiology of Aging
Publisher: Elsevier BV
Published: 2004-07
Volume: 25
Issue: 6
Pages: 783-793
ISSN: 0197-4580 (ISSN-L)
DOI: 10.1016/j.neurobiolaging.2003.07.007
OpenAlex: W2000636649
Cited by: 105
References: 55
Citations by year: 2026: 3 · 2024: 3 · 2023: 3 · 2022: 4 · 2021: 7 · 2020: 8 · 2019: 6 · 2018: 7 · 2017: 1 · 2016: 2 · 2015: 4 · 2014: 8 · 2013: 7 · 2012: 5
FWCI: 1.72
Type: journal article
Language: en
Open access: closed
Licence: www.elsevier.com/tdm/userlicense/1.0/ (tdm)
Locations: Neurobiology of Aging (publishedVersion)
PubMed (publishedVersion)
Funders: National Institute on Aging (AG 15964, R01AG015964)
Topics: Health Sciences › Medicine › Physiology › Alzheimer's disease research and treatments
Life Sciences › Neuroscience › Neurology › Neurological Disease Mechanisms and Treatments
Health Sciences › Medicine › Hematology › Blood Coagulation and Thrombosis Mechanisms
Keywords: thrombin, Alzheimer's disease, traumatic brain injury, neurotoxicity, cognitive impairment, reference memory, ventriculomegaly, hirudin, astrocyte activation, neurofilament phosphorylation, intracerebroventricular infusion
MeSH terms: Animals, Apolipoproteins E, Behavior, Animal, Brain, Cell Count, Dose-Response Relationship, Drug, Drug Interactions, Fibrinolytic Agents, Glial Fibrillary Acidic Protein, Hemostatics, Humans, Immunohistochemistry, Male, Memory Disorders, Motor Activity, Reaction Time, Thrombin, Blotting, Western, Neurofilament Proteins, Cell Death, Rats, Sprague-Dawley, Maze Learning, In Situ Nick-End Labeling, Hirudin Therapy, Rats

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Thrombin, a mediator of neurotoxicity and memory impairment

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