image: Phosphorylated n-cofilin (green) is present in the leading processes (arrowheads) of late-generated cortical neurons and in the cell bodies (asterisks) of early-generated neurons. Reelin (red) labels the marginal zone. Scale, 40 micrometers. See the article by Chai et al. for details. view more
Credit: J Neurosci. 2009 Jan 7;29(1):288-299.
1. Exocytosis Can Form Stable Membrane Deposits in Neurons
Joris de Wit, Ruud F. Toonen, and Matthijs Verhage.
Neurons secrete neuropeptides, neurotrophic factors, guidance molecules, and proteases via secretory dense-core vesicles. Although secretion of such molecules has been extensively studied in neuroendocrine cells, relatively little is known about release of these molecules by neurons. To remedy this, de Wit et al. labeled neuropeptide Y, brain-derived neurotrophic factor, semaphorin 3A, and the protease tPA (tissue plasminogen activator) with a pH-sensitive marker to track vesicle fusion in cultured mouse neurons. They found evidence that secretory vesicles in neurons sometimes exhibit partial fusion, in which only some of the cargo is released before the vesicle reforms and reacidifies. In addition, they discovered that neuronal exocytosis sometimes stably deposited vesicle cargo at the cell membrane. These stable deposits did not depend on the presence of extracellular matrix molecules, but instead appeared to result from interactions between basic residues of the cargo with the intravesicular matrix that persisted after incorporation of the vesicle into the plasma membrane.
2. Cofilin Links Reelin Signaling to Cytoskeletal Dynamics
Xuejun Chai, Eckart Förster, Shanting Zhao, Hans H. Bock, and Michael Frotscher.
During cerebral cortical development, layers are formed from the inside out, as newly generated neurons migrate past older neurons to form more superficial layers. Cajal-Retzius cells, which form the most superficial layer of the developing cortex, secrete the protein Reelin, which is required for proper layer formation. Although receptors, adaptor proteins, and several kinases involved in Reelin signaling have been identified, the downstream effectors of migratory control — which likely include cytoskeletal proteins — have remained elusive. Chai et al. report that one such effector is cofilin, an actin-depolymerizing protein that enables the formation of motile lamellipodia and is necessary for migration. They show that Reelin signaling increases phosphorylation of cofilin, which disrupts its ability to bind to actin and thereby increases neurite stability and hinders migration. They propose that the leading processes of migrating neurons become stabilized when they contact Reelin, and this allows proper migration of the neurons by nuclear translocation.
3. Oxytocin Improves Social Recognition in Humans
Ulrike Rimmele, Karin Hediger, Markus Heinrichs, and Peter Klaver.
In humans, oxytocin is best known for its effects during labor and lactation. Less is known about oxytocin's effects on social interactions in humans, although its effects in other animals have been extensively documented. In rodents, oxytocin is necessary for recognition of conspecifics, and it appears to reduce anxiety in social interactions and thus facilitate approach behaviors. Such effects are also thought to be present in humans, and deficiencies in oxytocin-mediated signaling have been implicated in social disorders such as autism and borderline personality disorder. This week, Rimmele et al. demonstrate a modest effect of oxytocin in a socially relevant task: face recognition. Oxytocin, administered intranasally before presentation of photographs, increased subjects' recognition of faces the next day. In contrast, oxytocin had no effect on recognition of objects. The largest effect appeared to be on the identification of novel faces, which oxytocin-treated subjects were less likely than controls to report as familiar.
4. Anti-Inflammatory Drug Mimics Effects of Omega-3 Fatty Acid
Cai Song, Xiang Yang Zhang, and Mehar Manku.
Omega-3 fatty acids (OFAs) are essential for normal cognitive function. OFA deficits have been linked to several neurological disorders including dementia, schizophrenia, and depression, and the OFA ethyl-eicosapentaenoate (EPA) has been used successfully to treat depression in humans. To gain insight into the molecular underpinnings of depression and how they are affected by EPA, Song et al. examined levels of inflammatory mediators and nerve growth factor (NGF) in olfactory bulbectomized rats, which show many of the behavioral, neural, and immunological changes observed in depressed humans. Bulbectomy increased phospholipase A2 and corticotrophin-releasing hormone expression in hypothalamus, increased interleukin-1β, prostaglandin E2, and corticosterone in blood, decreased expression of NGF in hippocampus, and slowed spatial learning. All these effects were prevented by treatment with EPA or an anti-inflammatory drug. The results support models of depression based on inflammation and reduced neurotrophic factor expression, and suggest that OFAs ameliorate depression by acting on these pathways.
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