Adult neurogenesis and its role in neuropsychiatric disease, brain repair and normal brain function.

Neural stem/progenitor cells (NSPCs) in the mammalian brain retain the ability to generate new neurones throughout life in discrete brain regions, through a process called adult neurogenesis. Adult neurogenesis, a dramatic form of adult brain circuitry plasticity, has been implicated in physiological brain function and appears to be of pivotal importance for certain forms of learning and memory. In addition, failing or altered neurogenesis has been associated with a variety of brain diseases such as major depression, epilepsy and age-related cognitive decline. Here we review recent advances in our understanding of the basic biology underlying the neurogenic process in the adult brain, focusing on mechanisms that regulate quiescence, proliferation and differentiation of NSPCs. In addition, we discuss how neurogenesis influences normal brain function, and in particular its role in memory formation, as well as its contribution to neuropsychiatric diseases. Finally, we evaluate the potential of targeting endogenous NSPCs for brain repair.

A functional role for adult hippocampal neurogenesis in spatial pattern separation.

The dentate gyrus (DG) of the mammalian hippocampus is hypothesized to mediate pattern separation-the formation of distinct and orthogonal representations of mnemonic information-and also undergoes neurogenesis throughout life. How neurogenesis contributes to hippocampal function is largely unknown. Using adult mice in which hippocampal neurogenesis was ablated, we found specific impairments in spatial discrimination with two behavioral assays: (i) a spatial navigation radial arm maze task and (ii) a spatial, but non-navigable, task in the mouse touch screen. Mice with ablated neurogenesis were impaired when stimuli were presented with little spatial separation, but not when stimuli were more widely separated in space. Thus, newborn neurons may be necessary for normal pattern separation function in the DG of adult mice.

[Reducing approach-associated morbidity in fracture dislocation of the femoral head--a longitudinal study (1982-2000)]. / Reduktion der zugangsassoziierten Morbidität bei Pipkinfrakturen - Eine Verlaufsbeobachtung (1982-2000).

Fractures of the femoral head occur during displacement injuries of the hip joint (Pipkin-type fractures). Reasons are high-energy traumas, usually dash-board injuries. Typical complications are posttraumatic necrosis of the femoral head (prevalence according to the literature: 15-66 %), and arthritis of the hip joint. It is yet uncertain, however, whether the type of surgical approach can influence the rate of necrosis. From June 1982 to December 2000, a total of 30 patients underwent surgery for Pipkin-type fractures, with 28 of them being posterior displacements, and 2 being anterior ones. Average age was 35.8 years, 2/3 were male, and 1/3 female. Total hip prosthesis was implanted primarily in 4 cases. 26 underwent osteosynthesis. Anterior displacements were stabilized via a lateral approach, whereas posterior ones were managed via a posterior approach. Reason for this procedure was the intention to use the one side of the joint-capsule for approach, that had been torn already by the displacement-injury. 21 of 26 operatively stabilized patients were followed-up between 6 and 54 months postoperatively. With this regimen of treatment, we had to face no case of necrosis of the femoral head. For fracture displacement of the femoral head we therefore suggest a posterior approach in posterior displacement, as well as an anterior approach for anterior displacement. Using this principle, rate of necrosis of the femoral head may clearly diminish (in our series 0 out of 21).

The polo-like protein kinases Fnk and Snk associate with a Ca(2+)- and integrin-binding protein and are regulated dynamically with synaptic plasticity.

In order to stabilize changes in synaptic strength, neurons activate a program of gene expression that results in alterations of their molecular composition and structure. Here we demonstrate that Fnk and Snk, two members of the polo family of cell cycle associated kinases, are co-opted by the brain to serve in this program. Stimuli that produce synaptic plasticity, including those that evoke long-term potentiation (LTP), dramatically increase levels of both kinase mRNAs. Induced Fnk and Snk proteins are targeted to the dendrites of activated neurons, suggesting that they mediate phosphorylation of proteins in this compartment. Moreover, a conserved C-terminal domain in these kinases is shown to interact specifically with Cib, a Ca(2+)- and integrin-binding protein. Together, these studies suggest a novel signal transduction mechanism in the stabilization of long-term synaptic plasticity.