VitaminAlizée333
03-06-2018, 02:07 PM
Some studies compelling the idea that the Brain is shapeable organ.
"Complex environment experience rescues impaired neurogenesis, enhances synaptic plasticity, and attenuates neuropathology in familial Alzheimer’s disease-linked APPswe/PS1ΔE9 mice"
The “enriched environment” experimental paradigm (28), was instrumental in demonstrating that brain structure is dynamically responsive to experience, even in adults (29,30,31). In an enriched environment, the animals are exposed to a complex array of stimuli (e.g., toys, obstacles, and tunnels), allowed freedom to move and exercise, and provided with more social stimulation than animals housed in standard laboratory conditions. Numerous studies indicate that environmental enrichment induces dendritic growth, stimulates dendritic branching, promotes the formation of new dendritic spines, enhances hippocampal neurogenesis, and results in increased numbers of synapses per neuron in many forebrain structures (32,33,34,35). Enrichment also enhances memory function in various learning tasks (31, 36,37,38,39).
These attributes raised the question of whether enrichment-induced brain plasticity would prevent or attenuate neuropathology in neurodegenerative diseases, particularly in AD. Using the enriched environment paradigm, we and others have shown that modulation of environmental factors significantly attenuates steady-state levels of Aβ and reduces extent of amyloid deposits in the brains of transgenic mice harboring FAD-linked APP and PS1 mutations (40,41,42,43). However, using different experimental conditions that affect variables such as duration of treatment related to the onset of deposition, some studies found no change in amyloid levels (44, 45) or even an increase (46).
"Discovery of nigral dopaminergic neurogenesis in adult mice"
Discovery of DA neurogenesis in adult mammals provides an opportunity to harness this naturally occurring process for therapeutic benefit. This will require locating and characterizing the DA progenitor cells responsible. Characterization of this process in vivo will potentially allow for modeling in cell culture systems that could expedite new therapeutic invention strategies. Such a system might facilitate drug screening efforts to modulate this process. In addition, furthering our understanding of adult DA neurogenesis will better inform stem cell replacement therapy for PD. Previous clinical trials have utilized fetal tissue with little manipulation or standardization prior to transplantation into PD patients (Freed et al., 2001; Olanow et al., 2003). This was believed to underlie the outcome variability from these studies. Understanding DA progenitor expression markers will permit differentiation in cell culture toward the appropriate phenotype and serve as a consistent source for transplantation therapy. Theoretically, this source material could be provided by the patient themselves using iPSC methods. Finally, the discovery of adult neurogenesis for DA neurons adds to the limited number of neural populations reported to experience this phenomenon and enhances our collective foundational knowledge of brain biology.
"Enriched and Deprived Sensory Experience Induces Structural Changes and Rewires Connectivity during the Postnatal Development of the Brain"
Although until relatively recent times it was believed that brain lost plasticity after the end of the critical period remaining fixed in adulthood, now it is well accepted that the adult brain maintains certain degree of plasticity to cope with a changing environment throughout life [14], like an extended critical period. Throughout numerous studies, it has been found that a number of interventions can promote plasticity in adult rodents, including environmental enrichment [31], visual deprivation [32], previous monocular deprivation of the same eye [33], enzymatic degradation of the extracellular matrix [26], stimulation of histone acetylation [34], and the antidepressant fluoxetine [35].
The best studied model of age-dependent cortical plasticity is ocular dominance (OD), achieved by monocular deprivation (MD). Neurons in the binocular visual cortex respond to inputs from both eyes but are dominated by the contralateral eye (in rodents), and monocular deprivation induces a shift in the ocular dominance of binocular neurons towards the open eye. The ocular dominance is most pronounced in young animals during postnatal development (P25), is reduced in young adults (P95), and is absent in fully mature animals older than 110 days of age [36].
To date, most studies and efforts have focused on young animals, but the studies of the last years have opened a new window for studies of plasticity in adults and their therapeutic application.
"Complex environment experience rescues impaired neurogenesis, enhances synaptic plasticity, and attenuates neuropathology in familial Alzheimer’s disease-linked APPswe/PS1ΔE9 mice"
The “enriched environment” experimental paradigm (28), was instrumental in demonstrating that brain structure is dynamically responsive to experience, even in adults (29,30,31). In an enriched environment, the animals are exposed to a complex array of stimuli (e.g., toys, obstacles, and tunnels), allowed freedom to move and exercise, and provided with more social stimulation than animals housed in standard laboratory conditions. Numerous studies indicate that environmental enrichment induces dendritic growth, stimulates dendritic branching, promotes the formation of new dendritic spines, enhances hippocampal neurogenesis, and results in increased numbers of synapses per neuron in many forebrain structures (32,33,34,35). Enrichment also enhances memory function in various learning tasks (31, 36,37,38,39).
These attributes raised the question of whether enrichment-induced brain plasticity would prevent or attenuate neuropathology in neurodegenerative diseases, particularly in AD. Using the enriched environment paradigm, we and others have shown that modulation of environmental factors significantly attenuates steady-state levels of Aβ and reduces extent of amyloid deposits in the brains of transgenic mice harboring FAD-linked APP and PS1 mutations (40,41,42,43). However, using different experimental conditions that affect variables such as duration of treatment related to the onset of deposition, some studies found no change in amyloid levels (44, 45) or even an increase (46).
"Discovery of nigral dopaminergic neurogenesis in adult mice"
Discovery of DA neurogenesis in adult mammals provides an opportunity to harness this naturally occurring process for therapeutic benefit. This will require locating and characterizing the DA progenitor cells responsible. Characterization of this process in vivo will potentially allow for modeling in cell culture systems that could expedite new therapeutic invention strategies. Such a system might facilitate drug screening efforts to modulate this process. In addition, furthering our understanding of adult DA neurogenesis will better inform stem cell replacement therapy for PD. Previous clinical trials have utilized fetal tissue with little manipulation or standardization prior to transplantation into PD patients (Freed et al., 2001; Olanow et al., 2003). This was believed to underlie the outcome variability from these studies. Understanding DA progenitor expression markers will permit differentiation in cell culture toward the appropriate phenotype and serve as a consistent source for transplantation therapy. Theoretically, this source material could be provided by the patient themselves using iPSC methods. Finally, the discovery of adult neurogenesis for DA neurons adds to the limited number of neural populations reported to experience this phenomenon and enhances our collective foundational knowledge of brain biology.
"Enriched and Deprived Sensory Experience Induces Structural Changes and Rewires Connectivity during the Postnatal Development of the Brain"
Although until relatively recent times it was believed that brain lost plasticity after the end of the critical period remaining fixed in adulthood, now it is well accepted that the adult brain maintains certain degree of plasticity to cope with a changing environment throughout life [14], like an extended critical period. Throughout numerous studies, it has been found that a number of interventions can promote plasticity in adult rodents, including environmental enrichment [31], visual deprivation [32], previous monocular deprivation of the same eye [33], enzymatic degradation of the extracellular matrix [26], stimulation of histone acetylation [34], and the antidepressant fluoxetine [35].
The best studied model of age-dependent cortical plasticity is ocular dominance (OD), achieved by monocular deprivation (MD). Neurons in the binocular visual cortex respond to inputs from both eyes but are dominated by the contralateral eye (in rodents), and monocular deprivation induces a shift in the ocular dominance of binocular neurons towards the open eye. The ocular dominance is most pronounced in young animals during postnatal development (P25), is reduced in young adults (P95), and is absent in fully mature animals older than 110 days of age [36].
To date, most studies and efforts have focused on young animals, but the studies of the last years have opened a new window for studies of plasticity in adults and their therapeutic application.