Digoxin Exhibits Neuroprotective Properties in a Rat Model of Dementia

• Published in: Neurochemical research Vol. 47; no. 5; pp. 1290 - 1298
• Main Authors: Erdogan, Mumin Alper, Kirazlar, Mehmet, Yigitturk, Gurkan, Erbas, Oytun
• Format: Journal Article
• Language: English
• Published: New York Springer US 01.05.2022; Springer Nature B.V
• Subjects: Alzheimer Disease - chemically induced; Alzheimer Disease - drug therapy; Alzheimer Disease - pathology; Alzheimer's disease; Animal models; Animals; Avoidance learning; Biochemistry; Biomedical and Life Sciences; Biomedicine; Brain; CA1 Region, Hippocampal; Cell Biology; Cell death; Choline; Cholinergics; Cognitive ability; Dementia; Dementia disorders; Digoxin; Digoxin - metabolism; Digoxin - pharmacology; Digoxin - therapeutic use; Disease Models, Animal; Etiology; Hippocampus; Hippocampus - metabolism; Impairment; Inflammation; Latency; Maze Learning; Neurochemistry; Neurodegenerative diseases; Neurology; Neuroprotection; Neuroprotective Agents - metabolism; Neuroprotective Agents - pharmacology; Neuroprotective Agents - therapeutic use; Neurosciences; Older people; Original Paper; Rats; Rats, Wistar; Signs and symptoms; Streptozocin; Streptozocin - pharmacology; Tumor necrosis factor-TNF; Tumor necrosis factor-α; Ventricle (lateral); Neuroprotection; Alzheimer’s disease; Digoxin; Streptozotocin; Hippocampus
• ISSN: 0364-3190; 1573-6903; 1573-6903
• DOI: 10.1007/s11064-022-03528-w

Alzheimer's disease (AD) is by far the most common cause of cognitive impairment in older adults. Current treatments are entirely focused on the symptoms of AD. A complex etiology for AD has been proposed recently, in which AD leads in elevated levels of inflammation. We previously studied digoxin's involvement in the sporadic-AD intracerebroventricular (ICV)-streptozotocin (STZ) animal model due to its anti-inflammatory and neuroprotective characteristics. 18 adult sprague–dawley rats were split into three groups: control (n = 6), STZ + Saline (n = 6), and STZ + Digoxin (n = 6). Twelve AD-induced rats were split into two groups using stereotaxy five days after STZ injection (3 mg/kg) into both lateral ventricles: one group got digoxin (0.1 mg/kg/day, i.p.) for three weeks, while the other group received saline. Following treatment, each subject was subjected to a passive avoidance learning (PAL) test, followed by brain tissue harvesting. The levels of tumor necrosis factor-alpha (TNF-α) and choline acetyl transferase (ChAT) were measured in the brain, and neurons were counted using Cresyl violet staining in cornu ammonis-1 (CA1) and cornu ammonis-3 (CA3) cornu ammonis (CA3). ICV-STZ significantly shortened PAL latency, increased brain TNF-α levels, decreased brain ChAT activity, and decreased hippocampus neuron number. On the other hand, digoxin significantly reduced all of these STZ-induced deleterious effects. Digoxin significantly rescued rats from memory loss caused by ICV-STZ by decreasing hippocampal cell death, neuroinflammation, and cholinergic deficiency. These findings suggest that digoxin may be beneficial in treating cognitive impairment and Alzheimer's disease.