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Plasticity, and in particular, neurogenesis, is a promising target to treat and prevent a wide variety of diseases (e.g., epilepsy, stroke, dementia). There are different types of plasticity, which vary with age, brain region, and species. These observations stress the importance of defining plasticity along temporal and spatial dimensions. We review recent studies focused on brain plasticity across the lifespan and in different species. One main theme to emerge from this work is that plasticity declines with age but that we have yet to map these different forms of plasticity across species. As part of this effort, we discuss our recent progress aimed to identify corresponding ages across species, and how this information can be used to map temporal variation in plasticity from model systems to humans.

Exposure to particles of high energy and charge can disrupt the neuronal systems as well as the motor and cognitive behaviors mediated by these systems in a similar fashion to that seen during the aging process. In the hippocampus, adult neurogenesis is affected both by aging and irradiation with ionizing particles. Likewise, the maturation of newly formed cells in this region as measured by PSA-NCAM expression is also altered by the aging process. The present study was designed to investigate the effects of 2.5 Gy of 1 GeV/n 56Fe particles on neurogenesis using the nuclear proliferation marker 5-bromodeoxyuridine (BrdU and PSA-NCAM expression in the dentate gyrus of rats exposed to whole-body irradiation or simply placed in the chamber without being irradiated. All subjects (n=10) were sacrificed 28 days after the last BrdU injection (50 mg/kg X 3 days) and their brains were processed for immunohistochemistry. Results illustrate a decrease in the number of BrdU-positive cells as well as different distribution of these cells in the dentate gyrus of irradiated animals. Additionally, irradiated subjects show decreased levels of PSA-NCAM expression. These changes are consistent with those found in aged subjects indicating that heavy-particle irradiation is an adequate model for the study of aging.

Dendritic and synapse remodeling are forms of structural plasticity that play a critical role in normal hippocampal function. Neural cell adhesion molecule (NCAM) and its polysialylated form (PSA-NCAM) participate in neurite outgrowth and synapse formation and plasticity. However, it remains unclear whether they contribute to dendritic retraction and synaptic disassembly. Cultured hippocampal neurons exposed to glutamate (5 µM) showed a reduced MAP-2 (+) area in the absence of neuronal death 24 h after the insult. Concomitantly, synapse loss, revealed by decreased synaptophysin and post-synaptic density-95 cluster number and area, together with changes in NCAM and PSA-NCAM levels were found. Dendritic atrophy and PSA-NCAM reduction proved NMDA-receptor dependent. Live-imaging experiments evidenced dendritic atrophy 4 h after the insult; this effect was preceded by smaller NCAM clusters (1 h) and decreased surface and total PSA-NCAM levels (3 h). Simultaneously, total NCAM cluster number and area remained unchanged. The subsequent synapse disassembly (6 h) was accompanied by reductions in total NCAM cluster number and area. A PSA mimetic peptide prevented both the dendritic atrophy and the subsequent synaptic changes (6 h) but had no effect on the earliest synaptic remodeling (3 h). Thus, NCAM-synaptic reorganization and PSA-NCAM level decrease precede glutamate-induced dendritic atrophy, whereas the NCAM level reduction is a delayed event related to synapse loss. Consequently, distinctive stages in PSA-NCAM/NCAM balance seem to accompany glutamate-induced dendritic atrophy and synapse loss. Fil: Podestá, María Fernabda. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Instituto de Investigaciones Farmacológicas. Universidad de Buenos Aires. Facultad de Farmacia y Bioquímica. Instituto de Investigaciones Farmacológicas; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Instituto de Biología Celular y Neurociencia "Prof. Eduardo de Robertis". Universidad de Buenos Aires. Facultad de Medicina. Instituto de Biología Celular y Neurociencia ; Argentina. Universidad de Buenos Aires. Facultad de Farmacia y Bioquímica. Departamento de Farmacología. Cátedra de Farmacología; Argentina Fil: Yam, Patricia. McGill University. Montreal Neurological Institute and Hospital; Canadá Fil: Codagnone, Martín Gabriel. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Instituto de Investigaciones Farmacológicas. Universidad de Buenos Aires. Facultad de Farmacia y Bioquímica. Instituto de Investigaciones Farmacológicas; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Instituto de Biología Celular y Neurociencia "Prof. Eduardo de Robertis". Universidad de Buenos Aires. Facultad de Medicina. Instituto de Biología Celular y Neurociencia ; Argentina. Universidad de Buenos Aires. Facultad de Farmacia y Bioquímica. Departamento de Farmacología. Cátedra de Farmacología; Argentina Fil: Uccelli, Nonthué Alejandra. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Instituto de Investigaciones Farmacológicas. Universidad de Buenos Aires. Facultad de Farmacia y Bioquímica. Instituto de Investigaciones Farmacológicas; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Instituto de Biología Celular y Neurociencia "Prof. Eduardo de Robertis". Universidad de Buenos Aires. Facultad de Medicina. Instituto de Biología Celular y Neurociencia ; Argentina. Universidad de Buenos Aires. Facultad de Farmacia y Bioquímica. Departamento de Farmacología. Cátedra de Farmacología; Argentina Fil: Colman, David. McGill University. Montreal Neurological Institute and Hospital; Canadá Fil: Reines, Analia Gabriela. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Instituto de Investigaciones Farmacológicas. Universidad de Buenos Aires. Facultad de Farmacia y Bioquímica. Instituto de Investigaciones Farmacológicas; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Instituto de Biología Celular y Neurociencia "Prof. Eduardo de Robertis". Universidad de Buenos Aires. Facultad de Medicina. Instituto de Biología Celular y Neurociencia ; Argentina. Universidad de Buenos Aires. Facultad de Farmacia y Bioquímica. Departamento de Farmacología. Cátedra de Farmacología; Argentina

Polysialic acid (PSA) is a highly hydrated polymer whose presence at the cell surface can reduce cell interactions, and thereby increase tissue and cellular plasticity. Given its ability to create a permissive environment for cell migration and axonal growth, the potential of engineered overexpression of PSA to promote tissue repair has been explored in the adult CNS. Several promising results have been obtained that suggest that PSA engineering may become a valuable therapeutic tool.

NCAM is an abundant cell adhesion molecule known to be important during development. Together with its posttranslational modification consisting of the addition of the polysaccharide polysialic acid (PSA), NCAM has been classically implicated in the regulation - among other developmental functions - of neurite outgrowth and stabilization of synaptic connections. A large body of work has also demonstrated that NCAM is required in the adult brain for different behavioral functions. In this review, we focus on those studies that have shown a role of NCAM and PSA-NCAM in the regulation of emotional responses and in the learning and memory processes.

Increasing evidence indicates that adhesion molecules are critically involved in the regulation of mechanisms of synaptic plasticity including synapse formation, and also synaptic remodeling associated with changes in synaptic strength. Among these, the Neural Cell Adhesion Molecule (NCAM) and its polysialylated form PSA-NCAM are important candidates. Here, we review recent results that point to a possible role of these two molecules in regulating the structural properties of excitatory synapses - namely, the composition and stability of the postsynaptic density - thereby accounting for their contribution to mechanisms of synaptogenesis and activity-dependent synaptic plasticity.

Polysialic acid (PSA) is a highly hydrated polymer whose presence at the cell surface can reduce cell interactions, and thereby increase tissue and cellular plasticity. Given its ability to create a permissive environment for cell migration and axonal growth, the potential of engineered overexpression of PSA to promote tissue repair has been explored in the adult CNS. Several promising results have been obtained that suggest that PSA engineering may become a valuable therapeutic tool.