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Drug: Physical and Mental Activity Rewire Brain

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Living in stimulating, stress-free, safe surroundings with regular physical activity may seem like common sense advice to keep healthy. But research teams in France and the US are finding in animal  research  that  ‘enriched  environments’  and  consistent  physical  exercise  can  actually produce long-lasting positive changes to the brain. Could a specific environment  ‘treat’ drug addiction? As  therapy costs  increase, with often high relapse  rates,  current  research  in  France  on  ‘enriched  environments’  could  offer  valuableapproaches to treating addiction.  Scientists have known for some time that physically and mentally stimulating surroundings,  mimicking  anti-stress  effects  of  positive  life  experiences,  can  impact  the  brain  positively.Research on enriched environments is showing promise for normal development and aging, and for many  disorders,  including  preventing  development  of  drug  addiction.  Today  (17  July) Dr Marcello Solinas of the Institut de Physiologie et Biologie Cellulaire at the University of Poitiers described  rodent  studies  showing  that  environmental  enrichment  produces  not  just preventative, but also restorative effects on cocaine addiction. The  studies  found  that  enriched  environments  seem  to  rewire  the brain,  change  the way  the brain transmits chemicals, stimulate the brain’s ability to make new cells, and change the way some genes work, he said today at the IBRO World Congress of Neuroscience in Florence.  In  two groups of  cocaine-addicted mice,  those  in  ‘regular’ environments did not  recover  from addiction.  Another  group  were  housed

in  physically,  socially,  and mentally  stimulating,  safe environments;  with  bigger  cages,  social  interaction,  and  a  greater  —  regularly  changing  — variety  of  exercise  activities  and  toys.  After  30  days,  abnormal  addiction-related  behaviour disappeared,  and  the mice did not  relapse.  “Given  opportunities  to  seek drugs,  they did not;and brain areas usually active in addiction drug seeking were inactive,” said Dr Solinas.  “Addiction alters brain wiring in key areas,” explained Dr Solinas. Interestingly, his team found that environmental enrichment produced dramatic rewiring in those areas: the striatum, frontal cortex, and hippocampus. Also in the hippocampus, an area important in learning and memory, other research teams found increased production of new brain cells (neurogenesis).  Other  research  teams  additionally  found  that  environmental  enrichment  changes  how  some genes are  ‘expressed’: how  they  instruct cells  to work.   Drug addiction —  like other disorders and outside influences such as diet or stress — causes certain epigenetic changes, turning some genes on or off, and varying  their activity  level. But  “environmental enrichment  can alter  the structure  of  chromatin,  DNA’s  physical  packaging”,  said  Dr  Solinas,  “reconfiguring  situations made  inflexible  by  addiction,”  reactivating  or  silencing  genes  affected  epigenetically  by addiction.  As this research indicates stress as a key factor in addiction relapse, Dr Solinas explained that environmental  enrichment  can  be  seen  as  the  functional  opposite  of  stress,  preventing development of drug addiction, but also potentially  treating  it.  “The changes seem  to be  long lasting,” he said. “This data is relevant right away,” said Dr Solinas. For humans, “a safe stimulating environment could give a person a  sense of control over  their own  life”, enabling  them  to  feel proactive  in their  recovery.  “If  one  has  a  positive  environment,  it may  be  easier  to  stay  abstinent  or  not relapse.  If one’s brain can be rewired, one has more  tools so as  to possibly not care so much about, or to resist drugs in future.”  Addiction treatment failures may not be due to medication, mentioned Dr Solinas, but possibly to

  therapy  environments.  He  believes  that  safe,  physically  and  mentally  stimulating environments could be considered or even  ‘prescribed’ as part of  future drug  treatment plans. Drug  addicts’  living  conditions may  also  be  important  to  consider,  said  Dr  Solinas.  “If  one’s environment  is negative, unstimulating, and unsafe, one’s  risks after  therapy may be higher.” “Compared  to  developing  new  medications,  developing  enriched  environments  is  not  costly, risky, or complex to propose or follow up,” said Dr Solinas.  Dr Solinas plans involvement in a future human study on alcohol treatment, using exercise as a major aspect of environmental enrichment. Scientists have learned over the past decade that enriched environments and other stimuli can trigger  parts  of  the  adult  brain  to  generate  increased  amounts  of  new  brain  cells (neurogenesis). But Dr Henriette van Praag of the National Institute on Aging (NIA), part of the  National  Institutes  of  Health,  ,  today  described  current  rodent  research  indicating  that “physical exercise is the dominant neurogenic stimulus.”  Dr  van  Praag,  head  of  the  Neuroplasticity  and  Behavior  Unit  at  NIA’s  Laboratory  of Neurosciences in Baltimore, said that voluntary exercise in mice increased new brain cell growth in  the hippocampus,  a brain  area  crucial not  only  for neurogenesis, but  also  for  learning  and memory.  Exercise  also  enhanced  brain  rewiring,  and  improved memory  itself —  indicating  a connection between new brain cells and cognition.  Over several research studies, Dr van Praag and her team  found that mice housed  for several weeks with  running wheels  had more  new  hippocampal  neurons  than  sedentary mice.  These more  active  mice,  tested  on  spatial  learning  (maze  and  pattern  discrimination)  tasks,  also showed  improved  memory  function.  Examining  brain  tissue  of  the  active  mice,  researchers additionally  found enhanced brain wiring (plasticity),  including strengthened neuronal dendritic trees, not  just  in  the hippocampus where neurogenesis occurs, but  also  in  other brain  areas, such as the cortex. Dr van

Praag  explained  that  the hippocampus  is  crucial  in generating new brain  cells. But  its ability to create them declines with age, and it is among the most vulnerable areas affected by neurodegenerative diseases such as Huntington’s and Alzheimer’s. “So we are focusing on how to  potentially  increase  production  of  these  new  cells,  in  mice,  and  possibly  improve  brain function.” As her  team are  interested  in  the hippocampus and  its potential  for  regeneration of neurons  in  vulnerable  brain  areas,  she  believes  these  findings  could  have  important implications, especially for the aging brain. Dr van Praag discussed how voluntary physical exercise might enhance or restore neurogenesis and memory function in normal aging mice, as well as in mouse models with neurodegenerative disease.  But  she  cautions  that  studies  are  still  ongoing,  and  in  some  diseases  such  as Huntington’s, research using mouse models is finding that exercise has no effect. With this greater understanding of exercise’s effect on adult hippocampal neurogenesis, Dr van Praag  hopes  this  research  area may  eventually  lead  to  enhancing  neurogenesis  by  restoring brain cells lost or damaged by neurodegenerative disorders, brain injury or normal aging. Both  research  areas  represent major  steps  forward  in  understanding  how  simple,  seemingly common  sense  lifestyle  strategies  could  also  point  the  way  to  important  new  therapy approaches.  IBRO,  the  International  Brain  Research  Organization,  is  the  global  neuroscience federation  dedicated  to  the  promotion  of  neuroscience  and  communication  between  brain researchers  around  the  world  with  special  emphasis  on  assisting  young  investigators  in  the developing world. Incorporated in 1961, IBRO now counts 84 member societies in 61 countries around  the  globe  with  a  membership  of  over  75,000  neuroscientists.  Celebrating  its  50th anniversary  in  2011.  Dr Marcello Solinas    – Dr Henriette van Praag. News from:INTERNATIONAL BRAIN RESEARCH ORGANIZATION 8th IBRO World Congress of Neuroscience Florence, Italy www.ibro.org

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