1. Krox20 –Nab2 Interactions in Myelination
Anne Desmazières, Laurence Decker, Jean-Michel Vallat, Patrick Charnay, and Pascale Gilardi-Hebenstreit
The transcription factor Krox20 controls expression of genes that are essential for maturation of myelin sheaths. To study the mechanisms underlying myelination, Desmazières et al. produced transgenic mice that express a mutant form of Krox20 that causes congenital hypomyelinating neuropathy in humans: a mutation that causes a single amino acid substitution, which disrupts interaction between Krox20 and its cofactor Nab2. During the first 2.5 postnatal weeks, myelination proceeded slowly in mutant Krox20 mice, and the mice developed tremors and lost coordination. Between postnatal days 17 and 20, when myelination is completed in wild-type mice, the slow myelination in mutants stopped, and myelinated axons rapidly lost their sheaths. Macrophages infiltrated the nerves, and mice died by day 21. Although Krox20 is also important for hindbrain patterning, this patterning was unaffected by the mutation. Thus, interactions between Krox20 and Nab2 appear essential for Krox20 function in peripheral myelination, but not in hindbrain patterning.
2. Synaptic Maintenance by Cbln1
Aya Ito-Ishida, Eriko Miura, Kyoichi Emi, Keiko Matsuda, Takatoshi Iijima, Tetsuro Kondo, Kazuhisa Kohda, Masahiko Watanabe, and Michisuke Yuzaki
Precerebellin (Cbln1), a protein produced and secreted by cerebellar granule cells, is required to maintain synapses between granule cell parallel fibers (PFs) and Purkinje cells (PCs), according to Ito-Ishida et al. Previously, cbln1-null mice were found to be ataxic and to have fewer PF–PC synapses than normal. Ito-shida et al. now report that recombinant Cbln1 restores synaptic function to these mice in vitro and in vivo. In cerebellar slices from knock-out mice, Cbln1 rapidly increased to wild-type levels the frequency of PC miniature EPSCs and the amplitude of evoked EPSCs. Injecting Cbln1 in vivo restored movement and improved coordination of knock-out mice, and electron microscopy revealed that Cbln1 reduced the number of PC dendritic spines that lacked presynaptic contacts. These effects peaked 4 d after injection, but performance and synaptic density returned to original levels by 3 weeks after injection, indicating that continual presence of Cbln1 is required for synapse formation and maintenance.
3. Maternal Care and Contextual Fear Learning
Danielle L. Champagne, Rosemary C. Bagot, Felisa van Hasselt, Ger Ramakers, Michael J. Meaney, E. Ronald de Kloet, Marian Joëls, and Harm Krugers
Postnatal maternal behaviors impact the ability of animals to learn later in life. Champagne et al. recorded licking and grooming behaviors of mother rats during the first 6 d after birth, then waited 2–3 months before comparing hippocampal properties in pups that had received the least licking and grooming to those that had received the most. Dendritic length and spine density were reduced in minimally groomed rats. Moreover, minimally groomed rats did not exhibit long-term potentiation (LTP) after 60 min of tetanic stimulation. Surprisingly, corticosterone—which is elevated in the hippocampus during stress and reduced LTP in maximally groomed rats—increased LTP in minimally groomed rats. In addition, minimally groomed rats learned stressful contexts better than maximally groomed rats did: when trained to associate a box with an electric shock, minimally groomed rats froze more often when returned to the box (indicating greater contextual fear learning) than did maximally groomed rats.
4. Phagocytosis of Active Neutrophils by Microglia
Jens Neumann, Steven Sauerzweig, Raik Rönicke, Frank Gunzer, Klaus Dinkel, Oliver Ullrich, Matthias Gunzer, and Klaus G. Reymann
Ischemia damages the brain by depriving cells of oxygen and glucose, but it also activates microglia and allows immune cells—including polymorphonuclear neutrophils (PMNs)—to enter the brain, causing additional damage. Contradictory evidence has obscured the relative roles of PMNs and microglia in ischemic damage; but Reymann et al. now bring some clarity by presenting results from an in vitro model of ischemia in which hippocampal slices were subject to oxygen and glucose deprivation (OGD) and then exposed to PMNs and/or microglia. In the absence of OGD, exogenous cells had no effect on neuronal survival. After OGD, however, PMNs greatly increased damage, causing rapid loss of axons, dendrites, and neurons. In contrast, microglia reduced OGD-induced damage, whether or not PMNs were present. Both endogenous and exogenous microglia were observed engulfing apoptotic and even motile PMNs. Blocking integrin and lectin receptors blocked both the engulfment of PMNs and the neuroprotective effects of microglia.
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