Enriched environments, experience-dependent plasticity and disorders of the nervous system

Nithianantharajah, Jess; Hannan, Anthony J.

doi:10.1038/nrn1970

Cited by 1,499 publications

(1,244 citation statements)

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“…EE promotes various plasticity mechanisms in the hippocampus, including bdnf gene upregulation, enhanced dendritic branching, and the stimulation of adult neurogenesis [234][235][236][237], reminiscent of our observations that CSP-TTK21 activates CBP/p300 activity. Furthermore, CBP-deficient mice present no response to the beneficial effect of EE on the induction and enhancement of spatial navigation capabilities during neurogenesis, highlighting the contribution of CBP to EE effects [233].…”

Section: Discussionsupporting

confidence: 72%

Acetyltransferases (HATs) as Targets for Neurological Therapeutics

et al. 2013

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The acetylation of histone and non-histone proteins controls a great deal of cellular functions, thereby affecting the entire organism, including the brain. Acetylation modifications are mediated through histone acetyltransferases (HAT) and deacetylases (HDAC), and the balance of these enzymes regulates neuronal homeostasis, maintaining the pre-existing acetyl marks responsible for the global chromatin structure, as well as regulating specific dynamic acetyl marks that respond to changes and facilitate neurons to encode and strengthen longterm events in the brain circuitry (e.g., memory formation). Unfortunately, the dysfunction of these finely-tuned regulations might lead to pathological conditions, and the deregulation of the HAT/HDAC balance has been implicated in neurological disorders. During the last decade, research has focused on HDAC inhibitors that induce a histone hyperacetylated state to compensate acetylation deficits. The use of these inhibitors as a therapeutic option was efficient in several animal models of neurological disorders. The elaboration of new cell-permeant HAT activators opens a new era of research on acetylation regulation. Although pathological animal models have not been tested yet, HAT activator molecules have already proven to be beneficial in ameliorating brain functions associated with learning and memory, and adult neurogenesis in wild-type animals. Thus, HAT activator molecules contribute to an exciting area of research.

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Section: Discussionsupporting

confidence: 72%

Acetyltransferases (HATs) as Targets for Neurological Therapeutics

et al. 2013

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“…We found that indeed EE caused a complex profile of gene expression which consisted of the regulation of 48 genes that are implicated in various functions including cell proliferation and differentiation, intracellular signalling, transcription and translation, as well as structural changes and cell metabolism. In what follows, we will discuss the possible role of some of these changes in modifying striatal functions observed after EE exposure and their potential implication in the resistance to drugs of abuse and neurotoxins that was previously reported (Bezard et al, 2003;Nithianantharajah and Hannan, 2006;Solinas et al, in press). …”

Section: Discussionmentioning

confidence: 82%

“…Since then, many studies in laboratory settings have confirmed and extended the notion that rodents reared in EE show improved learning and memory performance (Iuvone et al, 1996;Young et al, 1999). In addition, exposure to an EE has been shown to induce biochemical and structural changes in several brain regions in particular in the cortex and the hippocampus (Diamond et al, 1976;Kempermann et al, 1997;Nithianantharajah and Hannan, 2006;van Praag et al, 2000). Alterations include increased brain weight and size , increased neurotransmitter levels such as acetylcholine , serotonin and noradrenaline (Chaouloff, 1989), as well as enhanced gliogenesis (Diamond et al, 1966) and neurogenesis (Kempermann et al, 1997).…”

Section: Introductionmentioning

confidence: 93%

“…EE usually consists of larger cages containing several objects, often including a running wheel, which vary in composition, shape size, texture and color (Nithianantharajah and Hannan, 2006;van Praag et al, 2000). The positive effects of EE on animal learning and memory were first described in the 1940's by Hebb who allowed laboratory rats to roam freely in his house and observed behavioural improvements in these rats compared to ratshoused in standard laboratory conditions (Hebb, 1947).…”

Section: Introductionmentioning

confidence: 99%

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Environmental enrichment during adolescence regulates gene expression in the striatum of mice

et al. 2008

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We have previously shown that environmental enrichment decreases the activating and rewarding effects of the psych psychostimulant cocaine and increases resistance to the neurotoxic effect of the Parkinson-inducing drug MPTP. These effects were accompanied by an increase in the striatal expression of the neurotrophin BDNF, an increase in the striatal levels of delta-Fos B and by a decrease in striatal levels of the dopamine transporter, the main molecular target for cocaine and MPTP. Here, we used cDNA arrays to investigate the effects of rearing mice in enriched environments from weaning to adulthood on the profile of expression of genes in the striatum focusing on genes involved in intracellular signalling and functioning. We found that mice reared in an enriched environment show several alterations in the levels of mRNA coding for proteins involved in cell proliferation, cell differentiation, signal transduction, transcription and translation, cell structure and meta metabolism. Several of these findings were further confirmed by real-time quantitative PCR and, in the case of protein kinase C lambda, also by western blot. These findings are the first description of alterations in striatal gene expression by an enriched environment. The striatal gene expression regulation by environment that we report here may play a role in the resistance to the effects of drugs of abuse and dopaminergic neurotoxins previously reported.

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“…Empirical support for this view includes the following: stereotypic digging in caged gerbils (Meriones unguiculatus) is triggered specifically by the lack of naturalistic burrow-like structures [64]; the motor patterns Consistent with both ethological and neuroscientific accounts, captive animals' stereotypic behaviours are less prevalent and severe if individuals are raised and housed with 'enrichments', i.e. structures and stimuli that promote natural behaviour [22,27,56,57], and that are now well-documented with regard to enhancing CNS functioning/delaying the onset of neurological disorders [33]. Enriched individuals may also have reduced corticosteroid output, suggesting less stress and frustration [15], and anatomical and physiological changes in cortico-basal ganglia pathways that suggest more normal CNS functioning, e.g.…”

Section: Introductionmentioning

confidence: 75%

Frustration and perseveration in stereotypic captive animals: Is a taste of enrichment worse than none at all?

Latham

Mason

2010

Behavioural Brain Research

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a b s t r a c tStereotypic behaviours are common in animals in impoverished housing, arising from two complementary processes: (1) thwarted attempts to perform motivated behaviours; (2) forebrain dysfunction impeding normal behavioural inhibition. When enriched animals are moved to impoverished housing, they are sometimes protected against developing stereotypic behaviour, but in other cases become even more stereotypic than animals housed lifelong without enrichment. Negative contrast-induced frustration must occur in both scenarios. We hypothesise that sustained behavioural responses to this frustration are prevented in the former by normalised forebrain function, but exacerbated in the latter by forebrain dysfunction. ICRCD-1 mice reared in enriched or standard cages were re-caged at 3 months to standard conditions. Here, previously-enriched mice became far more stereotypic than mice reared from birth in such conditions. To investigate the role of frustration, we assessed both corticosterone output and motivation (break-point) to regain enrichments. We also assessed perseveration via extinction learning. As predicted, previously-enriched mice were as perseverative as standard-raised mice, and frustration seemed to play a causal role in their exacerbated stereotypic behaviour. Previously-enriched mice showed higher motivations to access enrichments, and only in this group did these correlate with corticosterone levels after re-caging; furthermore only in previously-enriched mice did corticosterone responses to re-caging predict stereotypic behaviour 30 days later (males only). All results need replicating and further investigation. However, they suggest for the first time that individual risk factors related to the HPA axis predict stereotypic behaviour following enrichment-removal, and that previously-enriched mice have lasting motivational differences from standard-raised mice, suggesting sustained behavioural effects related to the frustration of enrichment-loss.

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Enriched environments, experience-dependent plasticity and disorders of the nervous system

Cited by 1,499 publications

References 172 publications

Acetyltransferases (HATs) as Targets for Neurological Therapeutics

Acetyltransferases (HATs) as Targets for Neurological Therapeutics

Environmental enrichment during adolescence regulates gene expression in the striatum of mice

Frustration and perseveration in stereotypic captive animals: Is a taste of enrichment worse than none at all?

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