EPA Science Inventory

Mitochondrial bioenergetics in young, adult, middle-age and senescent brown Norway rats

Citation:

Pandya, J., A. Sebastian, J. Royland, R. MacPhail, AND P. Sullivan. Mitochondrial bioenergetics in young, adult, middle-age and senescent brown Norway rats. Presented at Society of Toxicology Meeting, Phoenix, AZ, March 23 - 27, 2014.

Description:

Mitochondria are central regulators of energy homeostasis and may play a pivotal role in mechanisms of cellular senescence and age-related neurodegenerative and metabolic disorders. However, mitochondrial bioenergetic parameters have not been systematically evaluated under identical physiological conditions within multiple organ samples in diverse age-groups. In the present study, we used the Seahorse Extracellular Flux Analyzer (Seahorse Bioscience XF-24) to compare four different life- stages [i.e. 1 Month- Young (Y), 4 Month- Adult (A), 12 Month- Middle-Aged (M) and 24 Month- Old-Aged (0)] of Brown Norway rats (n=5 animals/group). Mitochondrial (15-40 pg/well) bloenergetic parameters were evaluated together from five brain regions [brain stem (BS), frontal cortex (FC), cerebellum (CER), striatum (STR), hippocampus (HIP)] and three peripheral organs [heart (HRT), liver (LVR) lung (LNG)]. In general, all the regions of the brain followed identical patterns where the maximal respiratory capacities (State V and State Vs) were reduced with age (Y>A>M=O). The State Ill respiration in BS, CER and HIP demonstrated a similar pattern like State V (Y>A>M=O); whereas the FC and STR displayed highest State Ill rates in adult group (A>Y?O?M). The proton leak (State IV) remained unaffected. In peripheral organs, the State V and State III rates were highest in younger animals followed by gradual decline with aging as evident in both HRT (Y>A=O>M) and LNG (Y>A=O=M). In LVR, the NADH-Iinked bioenergetics remained unchanged whereas the FADH-Iinked maximal respiratory (State V5) rates increased gradually as a function of age (Y<A<M=O). In summary, the comparative data analysis of this study gives valuable insight into the metabolic status of various organs that could potentially lead to age-associated changes in neurodegenerative or metabolic disorders. Additionally, the observed changes in mitochondrial bioenergetics will serve as a basic platform to elucidate chemically-induced life-stage susceptibility mechanisms important in community health-related research. (This abstract does not necessarily reflect USEPA policy).

Purpose/Objective:

This abstract will be presented at the Society of Toxicology Meeting, March 23-27, 2014, Phoenix, AZ

URLs/Downloads:

TAD-14-008-ABSTRACT.PDF   (PDF,NA pp, 328.494 KB,  about PDF)

Record Details:

Record Type: DOCUMENT (PRESENTATION/ABSTRACT)
Completion Date: 07/21/2014
Record Last Revised: 07/21/2014
Record Created: 07/21/2014
Record Released: 07/21/2014
OMB Category: Other
Record ID: 281614

Organization:

U.S. ENVIRONMENTAL PROTECTION AGENCY

OFFICE OF RESEARCH AND DEVELOPMENT

NATIONAL HEALTH AND ENVIRONMENTAL EFFECTS RESEARCH LAB

TOXICOLOGY ASSESSMENT DIVISION

NEUROTOXICOLOGY BRANCH