Selenium prevents cognitive decline and oxidative damage in rat model of streptozotocin-induced experimental dementia of Alzheimer's type.
Selenium (Se), a nutritionally essential trace element with known antioxidant potential, protects the brain from oxidative damage in various models of neurodegeneration. Intracerebroventricular-streptozotocin (ICV-STZ) in rats causes impairment of brain glucose and energy metabolism along with oxidative damage and cholinergic dysfunction, and provides a relevant model for sporadic dementia of Alzheimer's type (SDAT). The present study demonstrates the therapeutic efficacy of Se on cognitive deficits and oxidative damage in ICV-STZ in rats. Male Wistar rats were pre-treated with sodium selenite, a salt of Se (0.1 mg/kg; body weight) for 7 days and then were injected bilaterally with ICV-STZ (3 mg/kg), while sham rats received the same volume of vehicle. After two ICV-STZ infusions, rats were tested for memory deficits in passive avoidance and Morris water maze (MWM) tests and then were sacrificed for biochemical and histopathological assays. ICV-STZ-infused rats showed significant loss in learning and memory ability, which were significantly improved by Se supplementation. A significant increase in thio-barbituric acid reactive species (TBARS), protein carbonyl (PC) and a significant decrease in reduced glutathione (GSH), antioxidant enzymes (glutathione peroxidase [GPx] and glutathione reductase [GR]) and adenosine triphosphate (ATP) in the hippocampus and cerebral cortex and choline acetyltransferase (ChAT) in hippocampus were observed in ICV-STZ rats. Se supplementation significantly ameliorated all alterations induced by ICV-STZ in rats. Our study reveals that Se, as a powerful antioxidant, prevents cognitive deficits, oxidative damage and morphological changes in the ICV-STZ rats. Thus, it may have a therapeutic value for the treatment of SDAT.
Ishrat
Tauheed
T
Department of Medical Elementology and Toxicology, Neurotoxicology Laboratory, Jamia Hamdard (Hamdard University), New Delhi, India. tauheedarshi@gmail.com
Parveen
Kehkashan
K
Khan
Mohd Moshahid
MM
Khuwaja
Gulrana
G
Khan
M Badruzzaman
MB
Yousuf
Seema
S
Ahmad
Ajmal
A
Shrivastav
Pallavi
P
Islam
Fakhrul
F
D000255:Adenosine Triphosphate / Q000378:metabolism; D000544:Alzheimer Disease / Q000139:chemically induced / Q000188:drug therapy*; D000818:Animals; D001362:Avoidance Learning / Q000187:drug effects; D001921:Brain / Q000187:drug effects* / Q000378:metabolism; D002795:Choline O-Acetyltransferase / Q000378:metabolism; D003072:Cognition Disorders / Q000139:chemically induced / Q000188:drug therapy*; D004195:Disease Models, Animal; D005978:Glutathione / Q000378:metabolism; D005979:Glutathione Peroxidase / Q000378:metabolism; D005980:Glutathione Reductase / Q000378:metabolism; D008297:Male; D018782:Maze Learning / Q000187:drug effects; D008568:Memory / Q000187:drug effects; D018696:Neuroprotective Agents / Q000008:administration & dosage / Q000494:pharmacology*; D018384:Oxidative Stress / Q000187:drug effects*; D050050:Protein Carbonylation / Q000187:drug effects; D051381:Rats; D017208:Rats, Wistar; D018038:Sodium Selenite / Q000008:administration & dosage / Q000494:pharmacology*; D013311:Streptozocin
D018696:Neuroprotective Agents; D013311:Streptozocin; D000255:Adenosine Triphosphate; D005979:Glutathione Peroxidase; D005980:Glutathione Reductase; D002795:Choline O-Acetyltransferase; D005978:Glutathione; D018038:Sodium Selenite