Voluntary Running Prevents Progressive Memory Decline and Increases Adult Hippocampal Neurogenesis and Growth Factor Expression after Whole-Brain Irradiation

Wong-Goodrich, Sarah J.E.; Pfau, Madeline L.; Flores, Catherine; Fraser, Jennifer; Williams, Christina L.; Jones, Lee W.

doi:10.1158/0008-5472.can-10-1854

Cited by 121 publications

(96 citation statements)

References 48 publications

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“…However, it also remains possible that genes and pathways possibly involved in cell turnover, and not dopamine signaling pathways in the NAc, may be an inherent driver in running phenotypes between HVRs vs. LVRs. This finding is quite intriguing, given that adult neurogenesis, while known to be increased in the dentate gyrus in response to voluntary exercise (33,48), has been less investigated in the NAc.…”

Section: Discussionmentioning

confidence: 99%

Phenotypic and molecular differences between rats selectively bred to voluntarily run high vs. low nightly distances

Roberts

Brown

Company

et al. 2013

American Journal of Physiology-Regulatory, Integrative and Comp

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Brown M, Booth FW. Phenotypic and molecular differences between rats selectively bred to voluntarily run high vs. low nightly distances. Am J Physiol Regul Integr Comp Physiol 304: R1024-R1035, 2013. First published April 3, 2013 doi:10.1152/ajpregu.00581.2012.-The purpose of the present study was to partially phenotype male and female rats from generations 8 -10 (G8 -G10) that had been selectively bred to possess low (LVR) vs. high voluntary running (HVR) behavior. Over the first 6 days with wheels, 34-day-old G8 male and female LVRs ran shorter distances (P Ͻ 0.001), spent less time running (P Ͻ 0.001), and ran slower (P Ͻ 0.001) than their G8 male and female HVR counterparts, respectively. HVR and LVR lines consumed similar amounts of standard chow with or without wheels. No inherent difference existed in PGC-1␣ mRNA in the plantaris and soleus muscles of LVR and HVR nonrunners, although G8 LVR rats inherently possessed less NADH-positive superficial plantaris fibers compared with G8 HVR rats. While day 28 body mass tended to be greater in both sexes of G9 -G10 LVR nonrunners vs. G9 -G10 HVR nonrunners (P ϭ 0.06), body fat percentage was similar between lines. G9 -G10 HVRs had fat mass loss after 6 days of running compared with their prerunning values, while LVR did not lose or gain fat mass during the 6-day voluntary running period. RNA deep sequencing efforts in the nucleus accumbens showed only eight transcripts to be Ͼ1.5-fold differentially expressed between lines in HVR and LVR nonrunners. Interestingly, HVRs presented less Oprd1 mRNA, which ties in to potential differences in dopaminergic signaling between lines. This unique animal model provides further evidence as to how exercise may be mechanistically regulated. selective breeding; exercise; genes; nucleus accumbens; RNA-seq APPROXIMATELY 97% OF US adults and 92% of adolescents are not meeting US daily physical activity guidelines for 30 and 60 min, respectively (44). The clinical significance of lack of sufficient daily physical activity is an increased prevalence of 35 chronic unhealthy conditions and premature death (5). Motivation, fitness, and genes are all associated with physical activity levels (4). Twin and family studies have shown that genetic factors contribute to variation in reported daily physical activity levels, with identical cotwins showing smaller intraindividual variation than nontwins (see Ref. 4 for references).Animal studies also suggest that brain mechanisms affect the quantity of daily voluntary running (14,21,22,36,38).One approach to obtain genetic information on genes and physical activity has been to employ a selective breeding model of physical activity in rodents. According to Rhodes et al. (35), selective breeding is a "powerful alternative" compared with knockout models in studying genotype-phenotype interactions, given that multiple genes contribute to complex phenotypes. Swallow et al. (42) have phenotyped their 10th generation of mice selected for the highest revolutions per day of wheel running, these being ...

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Section: Discussionmentioning

confidence: 99%

Phenotypic and molecular differences between rats selectively bred to voluntarily run high vs. low nightly distances

Roberts

Brown

Company

et al. 2013

American Journal of Physiology-Regulatory, Integrative and Comp

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“…Ekdahl et al (1) reported that the LPS-induced inflammation remarkably reduced the number of new neurons, the BrdU-immunoreactive cells double-labeled with NeuN in the subgranular zone of the dentate gyrus. On the other hand, physical exercise improved memory function and spatial learning ability through the enhancement of neurogenesis, which was ascertained by increasing the number of BrdU-and NeuN-double positive neurons (31).…”

Section: Discussionmentioning

confidence: 99%

Treadmill and wheel exercise alleviate lipopolysaccharide-induced short-term memory impairment by enhancing neuronal maturation in rats

Kim

Park

et al. 2012

Molecular Medicine Reports

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Abstract. Lipopolysaccharide (LPS) is an endotoxin derived from Gram-negative bacteria, which induces brain inflammation. LPS-induced brain inflammation deteriorates hippocampus-dependent cognitive deficits. In the present study, we investigated the effects of forced treadmill exercise and voluntary wheel exercise on short-term memory in relation to neuronal maturation in LPS-induced brain inflammation of rats. Brain inflammation in rats was induced by an injection of LPS into the cerebral ventricle. Short-term memory was evaluated using a step-down avoidance task. Cell proliferation in the hippocampal dentate gyrus was determined by 5-bromo-2'-deoxyuridine (BrdU), a marker of new cells, immunohistochemistry. Western blot analysis for the determination of doublecortin (DCX), a marker of immature neurons and neuronal nuclear antigen (NeuN), a marker of mature neurons, was performed. In the present study, LPS-induced brain inflammation impaired short-term memory by increasing DCX expression and suppressing NeuN expression. These results suggest that LPS-induced brain inflammation disturbs neuronal maturation. The number of BrdU-positive cells in the hippocampal dentate gyrus was increased by LPS injection. This increase in the number of BrdU-positive cells can be ascribed to the increase in the number of of immature neurons following LPS injection. On the other hand, forced treadmill exercise and voluntary wheel exercise improved brain inflammation-induced short-term memory impairment by suppressing DCX expression and increasing NeuN expression, enhancing neuronal maturation. Forced treadmill exercise and voluntary wheel exercise showed similar efficacy. From these results, it can be inferred that forced treadmill exercise and voluntary wheel exercise may improve memory function deteriorated by brain inflammation.

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“…57,58 It is now known that although radiation kills rapidly dividing neural progenitor cells, the more quiescent neural stem cells (NSCs) remain viable after brain radiation, albeit in a persistently quiescent state only modestly responsive to proneurogenic stimuli such as voluntary physical exercise and mitogenic stimulation. 60,93 Unfortunately, radiation's failure to kill quiescent NSCs mirrors its inability to kill quiescent glioma stem cells, which reestablish a typically more aggressive and resistant recurrent malignancy.…”

Section: Impact Of Radiation On Neurogenesis and Neuronal Functionmentioning

confidence: 99%

Radiation-induced brain injury: low-hanging fruit for neuroregeneration

Burns

Awad

et al. 2016

FOC

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Brain radiation is a fundamental tool in neurooncology to improve local tumor control, but it leads to profound and progressive impairments in cognitive function. Increased attention to quality of life in neurooncology has accelerated efforts to understand and ameliorate radiation-induced cognitive sequelae. Such progress has coincided with a new understanding of the role of CNS progenitor cell populations in normal cognition and in their potential utility for the treatment of neurological diseases. The irradiated brain exhibits a host of biochemical and cellular derangements, including loss of endogenous neurogenesis, demyelination, and ablation of endogenous oligodendrocyte progenitor cells. These changes, in combination with a state of chronic neuroinflammation, underlie impairments in memory, attention, executive function, and acquisition of motor and language skills. Animal models of radiation-induced brain injury have demonstrated a robust capacity of both neural stem cells and oligodendrocyte progenitor cells to restore cognitive function after brain irradiation, likely through a combination of cell replacement and trophic effects. Oligodendrocyte progenitor cells exhibit a remarkable capacity to migrate, integrate, and functionally remyelinate damaged white matter tracts in a variety of preclinical models. The authors here critically address the opportunities and challenges in translating regenerative cell therapies from rodents to humans. Although valiant attempts to translate neuroprotective therapies in recent decades have almost uniformly failed, the authors make the case that harnessing human radiation-induced brain injury as a scientific tool represents a unique opportunity to both successfully translate a neuroregenerative therapy and to acquire tools to facilitate future restorative therapies for human traumatic and degenerative diseases of the central nervous system.

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Voluntary Running Prevents Progressive Memory Decline and Increases Adult Hippocampal Neurogenesis and Growth Factor Expression after Whole-Brain Irradiation

Cited by 121 publications

References 48 publications

Phenotypic and molecular differences between rats selectively bred to voluntarily run high vs. low nightly distances

Phenotypic and molecular differences between rats selectively bred to voluntarily run high vs. low nightly distances

Treadmill and wheel exercise alleviate lipopolysaccharide-induced short-term memory impairment by enhancing neuronal maturation in rats

Radiation-induced brain injury: low-hanging fruit for neuroregeneration

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