Mitochondrial dysfunction: A crucial event in okadaic acid (ICV) induced memory impairment and apoptotic cell death in rat brain

Pradeep K. Kamat, Santoshkumar Tota, Rakesh Shukla, Shakir Ali, Abul Kalam Najmi, Chandishwar Nath

Research output: Contribution to journalArticlepeer-review

54 Scopus citations

Abstract

Mitochondrial abnormalities have been identified in a large proportion of neurodegenerative diseases. Recently we have reported that intracerebroventricular (ICV) administration of okadaic acid (OKA) causes memory impairment in rat. However involvement of mitochondrial function in OKA induced memory impairment and neuronal damage has not been determined. OKA (200 ng) was administered by ICV route. After 13th day of OKA administration memory function was evaluated by Morris Water Maze test. Following completion of behavioral studies on 16th day, mitochondrial membrane potential, Ca 2+ and reactive oxygen species were evaluated in mitochondrial preparation of cortex, hippocampus, striatum and cerebellum of rat brain. While ATP, mitochondrial activity, lipid peroxidation and nitrite were investigated in synaptosomal preparation of rat brain areas. The activities and mRNA expression of apoptotic factors, caspase-3 and caspase-9, were studied in rat brain regions. The neuronal damage was also confirmed by histopathological study. OKA treated rats showed memory impairment including increased Ca 2+ and reactive oxygen species and decreased mitochondrial membrane potential, ATP and mitochondrial activity in mitochondrial preparation. There was a significant increase in lipid peroxidation and nitrite in synaptosomal preparations. Preventive treatment daily for 13 days with antidementic drugs, donepezil (5 mg/kg, p.o) and memantine (10 mg/kg, p.o), significantly attenuated OKA induced mitochondrial dysfunction, apoptotic cell death, memory impairment and histological changes. Mitochondrial dysfunction appeared as a key factor in OKA induced memory impairment and apoptotic cell death. This study indicates that clinically used antidementic drugs are effective against OKA induced adverse changes at behavioral, cellular, and histological levels and mitochondrial dysfunction.

Original languageEnglish (US)
Pages (from-to)311-319
Number of pages9
JournalPharmacology Biochemistry and Behavior
Volume100
Issue number2
DOIs
StatePublished - Dec 2011
Externally publishedYes

Keywords

  • Apoptosis
  • Donepezil
  • Memantine
  • Memory impairment
  • Mitochondrial dysfunction
  • Okadaic acid
  • Oxidative stress

ASJC Scopus subject areas

  • Biochemistry
  • Toxicology
  • Pharmacology
  • Clinical Biochemistry
  • Biological Psychiatry
  • Behavioral Neuroscience

Fingerprint Dive into the research topics of 'Mitochondrial dysfunction: A crucial event in okadaic acid (ICV) induced memory impairment and apoptotic cell death in rat brain'. Together they form a unique fingerprint.

Cite this