title: Initiation of calorie restriction in middle-aged male rats attenuates aging-related motoric decline and bradykinesia without increased striatal dopamine.
abstract: Aging-related bradykinesia affects ∼ 15% of those reaching age 65 and 50% of those reaching their 80s. Given this high risk and lack of pharmacologic therapeutics, noninvasive lifestyle strategies should be identified to diminish its risk and identify the neurobiological targets to reduce aging-related bradykinesia. Early-life, long-term calorie restriction (CR) attenuates aging-related bradykinesia in rodents. Here, we addressed whether CR initiation at middle age could attenuate aging-related bradykinesia and motoric decline measured as rotarod performance. A 30% CR regimen was implemented for 6 months duration in 12-month-old male Brown-Norway Fischer 344 F1 hybrid rats after establishing individual baseline locomotor activities. Locomotor capacity was assessed every 6 weeks thereafter. The ad libitum group exhibited predictably decreased locomotor activity, except movement speed, out to 18 months of age. In contrast, in the CR group, movement number and horizontal activity did not decrease during the 6-month trial, and aging-related decline in rotarod performance was attenuated. The response to CR was influenced by baseline locomotor activity. The lower the locomotor activity level at baseline, the greater the response to CR. Rats in the lower 50th percentile surpassed their baseline level of activity, whereas rats in the top 50th percentile decreased at 6 weeks and then returned to baseline by 12 weeks of CR. We hypothesized that nigrostriatal dopamine tissue content would be greater in the CR group and observed a modest increase only in substantia nigra with no group differences in striatum, nucleus accumbens, or ventral tegmental area. These results indicate that initiation of CR at middle age may reduce aging-related bradykinesia, and, furthermore, subjects with below average locomotor activity may increase baseline activity. Sustaining nigral dopamine neurotransmission may be one component of preserving locomotor capabilities during aging.
authors.affiliation: Department of Pharmacology, Toxicology, & Neuroscience, Louisiana State University Health Sciences Center, Shreveport, LA, USA; Department of Pharmacology & Neuroscience, University of North Texas Health Science Center, Fort Worth, TX, USA. Electronic address: Michael.Salvatore@unthsc.edu.
authors.forename: Michael F
authors.initials: MF
authors.lastname: Salvatore
authors.affiliation: Pennington Biomedical Research Center, Louisiana State University, Baton Rouge, LA, USA.
authors.forename: Jennifer
authors.initials: J
authors.lastname: Terrebonne
authors.affiliation: Department of Pharmacology, Toxicology, & Neuroscience, Louisiana State University Health Sciences Center, Shreveport, LA, USA.
authors.forename: Victoria
authors.initials: V
authors.lastname: Fields
authors.affiliation: Department of Pharmacology, Toxicology, & Neuroscience, Louisiana State University Health Sciences Center, Shreveport, LA, USA.
authors.forename: Danielle
authors.initials: D
authors.lastname: Nodurft
authors.affiliation: Pennington Biomedical Research Center, Louisiana State University, Baton Rouge, LA, USA.
authors.forename: Cori
authors.initials: C
authors.lastname: Runfalo
authors.affiliation: Department of Pharmacology, Toxicology, & Neuroscience, Louisiana State University Health Sciences Center, Shreveport, LA, USA.
authors.forename: Brian
authors.initials: B
authors.lastname: Latimer
authors.affiliation: Pennington Biomedical Research Center, Louisiana State University, Baton Rouge, LA, USA.
authors.forename: Donald K
authors.initials: DK
authors.lastname: Ingram
mesh_terms: D000375:Aging / Q000378:metabolism / Q000502:physiology*; D000818:Animals; D031204:Caloric Restriction; D003342:Corpus Striatum / Q000378:metabolism; D004298:Dopamine / Q000378:metabolism / Q000502:physiology; D018476:Hypokinesia / Q000517:prevention & control*; D008019:Life Style; D008297:Male; D009043:Motor Activity / Q000502:physiology*; D011914:Rats, Inbred BN; D011916:Rats, Inbred F344; D045442:Rotarod Performance Test; D013378:Substantia Nigra / Q000378:metabolism; D009435:Synaptic Transmission / Q000502:physiology
chemical_list: D004298:Dopamine
keywords: Bradykinesia; Caloric restriction; Dopamine; Parkinsonism; Striatum; Substantia nigra