Environmental enrichment in adulthood eliminates neuronal death in experimental Parkinsonism

Department of Developmental Neurobiology, St. Jude Children's Research Hospital, Mail Stop 323, 332 North Lauderdale, Memphis, TN 38017, USA.
Molecular Brain Research (Impact Factor: 2). 04/2005; 134(1):170-9. DOI: 10.1016/j.molbrainres.2004.08.008
Source: PubMed


Idiopathic Parkinson's disease (PD) affects 2% of adults over 50 years of age. PD patients demonstrate a progressive loss of dopamine neurons in the substantia nigra pars compacta (SNpc). One model that recapitulates the pathology of PD is the administration of 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP). Here we show that exposure to an enriched environment (EE) (a combination of exercise, social interactions and learning) or exercise alone during adulthood, totally protects against MPTP-induced Parkinsonism. Furthermore, changes in mRNA expression would suggest that increases in glia-derived neurotrophic factors, coupled with a decrease of dopamine-related transporters (e.g. dopamine transporter, DAT; vesicular monoamine transporter, VMAT2), contribute to the observed neuroprotection of dopamine neurons in the nigrostriatal system following MPTP exposure. This non-pharmacological approach presents significant implications for the prevention and/or treatment of PD.

Download full-text


Available from: Richard J Smeyne,
  • Source
    • "Epilepsy Increased seizure resistance Increased exploratory activity (Open field) Improved spatial learning (Morris water maze) Decreased hippocampal cell death Increased neurogenesis Increased growth factor expression Enhanced expression of neuronal and synaptic plasticity mediators Young et al., 1999; Auvergne et al., 2002; Faverjon et al., 2002; Rutten et al., 2002; Koh et al., 2007; Korbey et al., 2008 Huntington's disease Delayed onset of motor deficits Improved spatial memory (Barnes maze, Morris water maze) Delays degenerative loss of cerebral volume Attenuates deficits in hippocampal neurogenesis Reduced aggregation of huntingtin protein fragments Increased growth factor expression Increased synaptic protein expression Van Dellen et al., 2000; Hockly et al., 2002; Spires et al., 2004; Lazic et al., 2006; Nithianantharajah et al., 2008; Wood et al., 2010 Alzheimer's disease Improved spatial learning and memory (Morris water maze, Barnes maze) Improved working memory (Radial arm water maze) Increased/decreased Aβ and amyloid deposition Increased neuronal progenitor cell proliferation Increased/decreased neurogenesis Decreased progenitor cell survival Increased growth factor expression Increased synaptophysin expression Jankowsky et al., 2003, 2005; Levi et al., 2003; Arendash et al., 2004; Wen et al., 2004; Lazarov et al., 2005; Berardi et al., 2007; Cracchiolo et al., 2007; Levi and Michaelson, 2007; Valero et al., 2011 Parkinson's disease Improved motor function (skilled reaching task) Decreased dopaminergic neuron and transporter loss Decreased cell death Increased growth factor expression Bezard et al., 2003; Faherty et al., 2005; Jadavji et al., 2006 Summary of findings from studies that have investigated the effects of EE after various neurological conditions. "
    [Show abstract] [Hide abstract]
    ABSTRACT: The brain's life-long capacity for experience-dependent plasticity allows adaptation to new environments or to changes in the environment, and to changes in internal brain states such as occurs in brain damage. Since the initial discovery by Hebb (1947) that environmental enrichment (EE) was able to confer improvements in cognitive behavior, EE has been investigated as a powerful form of experience-dependent plasticity. Animal studies have shown that exposure to EE results in a number of molecular and morphological alterations, which are thought to underpin changes in neuronal function and ultimately, behavior. These consequences of EE make it ideally suited for investigation into its use as a potential therapy after neurological disorders, such as traumatic brain injury (TBI). In this review, we aim to first briefly discuss the effects of EE on behavior and neuronal function, followed by a review of the underlying molecular and structural changes that account for EE-dependent plasticity in the normal (uninjured) adult brain. We then extend this review to specifically address the role of EE in the treatment of experimental TBI, where we will discuss the demonstrated sensorimotor and cognitive benefits associated with exposure to EE, and their possible mechanisms. Finally, we will explore the use of EE-based rehabilitation in the treatment of human TBI patients, highlighting the remaining questions regarding the effects of EE.
    Frontiers in Systems Neuroscience 09/2014; 8. DOI:10.3389/fnsys.2014.00156
  • Source
    • "No procedure for stopping the neurodegenerative process of Parkinson’s disease has so far been found13). A Previous studies have reported that training increases the nerve growth factors required to prevent and regenerate dopamine-producing nerve cells and the supply of oxygen14), decreases the severity of Parkinson’s disease15), and slows the degenerative process of the nerves16). "
    [Show abstract] [Hide abstract]
    ABSTRACT: [Purpose] This study was conducted to investigate the effect of balance and gait training on the recovery of the motor function in a Parkinson's disease animal models. [Subjects and Methods] A total of 40 mice were randomly classified into four groups with 10 in each group: Group I-Normal; Group II-Parkinson's disease and no training; Group III-Parkinson's disease and balance training was performed; and Group IV-Parkinson's disease and gait training. Parkinson's disease was induced by administration of MPTP to animals in Groups II-IV. Groups III and IV did training once a day, five days a week, for four weeks. Neurobehavioral evaluation was performed through the pole and open-field tests. Immunological evaluation was performed via TH (tyrosine hydroxylase) protein expression, using western blot analysis. [Results] In the result of the pole test, Groups III and IV showed significantly greater motor function recovery than to Group II. The results of the open-field test also showed that Groups III and IV had significantly greater motor function recovery than to Group II, and Group IV showed significantly greater motor function recovery than to Group III. Using western blot analysis, we determined that the expression of TH protein in the corpus striatum was greatest in group I, followed by Groups III and IV, and that Group II had the lowest TH protein expression in the corpus striatum. [Conclusion] The results of this study showed that balance and gait training were effective at recovering the motor functions of a Parkinson's disease animal models induced by MPTP, and that gait training was more effective than balance training.
    Journal of Physical Therapy Science 06/2014; 26(6):905-8. DOI:10.1589/jpts.26.905 · 0.39 Impact Factor
  • Source
    • "Several etiologies such as age, gender, and race (Piccinelli and Wilkinson, 2000; Gottlieb et al., 2004; Hedden and Gabrieli, 2004), stress (Lupien et al., 2009), socioeconomic status (Gilman et al., 2002; Lorant et al., 2003), metabolic disorders (Simon et al., 2006; Rinaldi et al., 2014), gene–environment interactions (Caspi and Moffitt, 2006), and neuroinflammation (Campbell, 2004; Ownby, 2010; Tansey and Goldberg, 2010) have been implicated for the impairment of brain function. Contrary to this, environmental enrichment (EE), a concept of " modifying the environment of captive animals to enhance their physical and psychological well-being by providing stimuli meeting their species-specific need " (Baumans, 2005), has been shown to slow down neuronal aging (Gould et al., 2000; Kempermann et al., 2002) and improve cognition, memory, behavior, and motor coordination in pre-clinical models of dementia, depression , Alzheimer's disease (AD), Parkinson's disease (PD), and Huntington's disease (Faherty et al., 2005; Jankowsky et al., 2005; Hannan, 2014). "
    [Show abstract] [Hide abstract]
    ABSTRACT: Recent studies on environmental enrichment (EE) have shown cytokines, cellular immune components (e.g. T lymphocytes, NK cells) and glial cells in causal relationship to EE in bringing out changes to neurobiology and behavior. The purpose of this review is to evaluate these neuroimmune mechanisms associated with neurobiological and behavioral changes in response to different EE methods. We systematically reviewed common research databases. After applying all inclusion and exclusion criteria, 328 articles remained for this review. Physical exercise, a form of EE, elicits anti-inflammatory and neuromodulatory effects through interaction with several immune pathways including IL-6 secretion from muscle fibers, reduced expression of TLR’s on monocytes and macrophages, reduced secretion of adipokines, modulation of hippocampal T cells, priming of microglia and upregulation of MKP-1 in CNS. In contrast, immunomodulatory roles of other enrichment methods are not studied extensively. Nonetheless, studies showing reduction in the expression of IL-1β and TNF-α in response to enrichment with novel objects and accessories suggest anti-inflammatory effects of novel environment. Likewise, social enrichment, though considered a necessity for healthy behavior, results in immunosuppression in socially defeated animals. This has been attributed to reduction in T lymphocytes, NK cells and IL-10 in subordinate animals. EE through sensory stimuli has been investigated to a lesser extent and the effect on immune factors has not been evaluated yet. Discovery of this multidimensional relationship between immune system, brain functioning and EE has paved a way towards formulating environ-immuno therapies for treating psychiatric illnesses with minimal use of pharmacotherapy. While the immuno-modulatory role of physical exercise has been evaluated extensively, more research is required to investigate neuroimmune changes associated with other enrichment methods.
    Frontiers in Cellular Neuroscience 04/2014; 8(1):97. DOI:10.3389/fncel.2014.00097 · 4.29 Impact Factor
Show more