Cellular/Molecular
Trading Secrets at the Synapse
Josef Spacek and Kristen M. Harris
(see pages 4233-4241)
Serial electron microscopy (EM) is a painstaking method generally used to give a high-resolution static image of neuropil. However, a snapshot at the right moment can provide clues to membrane dynamics at the synapse. This week Spacek and Harris provide enough snapshots by serial EM reconstructions to propose a novel and dynamic mechanism of transcellular communication in the rat hippocampus. They call it trans-endocytosis. They observed spine-like evaginations, originating primarily from dendritic spines, which were engulfed by adjacent cells to form double-membrane structures (spinules). Images of double-membrane structures within the cytoplasm supported the idea of trans-endocytosis. Spinules involving mushroom spines were associated primarily with presynaptic axons, whereas spinules involving thin spines were associated with axons or adjacent glial cells, indicating a highly ordered process. Although these studies do not reveal the function of this process, the authors suggest a number of intriguing possibilities, including synaptic remodeling or intercellular exchange of cytoplasmic and membrane components between cells.
Reconstruction of a spinule (turquoise) that emerges from a perforation in the postsynaptic density (surface area in red) and projects into a presynaptic axon (data not shown). See the article by Spacek and Harris for details.
Development/Plasticity/Repair
BMPs in the Development of Enteric Neurons
Alcmène Chalazonitis, Fabien D'Autréaux, Udayan Guha, Tuan D. Pham, Christophe Faure, Jason J. Chen, Daniel Roman, Lixin Kan, Taube P. Rothman, John A. Kessler, and Michael D. Gershon
(see pages 4266-4282)
The influence of the local environment drives the development of the enteric nervous system (ENS) that derives from the neural crest. Bone morphogenetic proteins (BMPs), not being deterred by their name, influence developmental processes in many tissues, including the gut. In this issue, Chalazonitis et al. set out to determine the role of BMP-2 and -4 on the specification and differentiation of enteric neurons. They examined the ENS of mice at embryonic day 12 when neurons first appear in the gut. BMPs, their cognate receptors, as well as several endogenous antagonists were identified in populations of neural crest-derived and non-crest-derived cells. Using transgenic mice that overexpress the endogenous antagonist noggin and thus sequester extracellular BMP, the authors find that BMP limits the size of the neuronal pool by encouraging postmitotic neuronal differentiation of proliferating cells. However, a subset of neurons expressing the trophic receptor TrkC was preferentially enhanced.
Behavioral/Systems/Cognitive
Collapse, Air, Stop, Bite: Controlling Ecdysis
Anthony C. Clark, Marta L. del Campo, and John Ewer
(see pages 4283-4292)
Steroid hormones coordinate molting, the process in insects of replacing the old exoskeleton to make room for growth. A series of behaviors are associated with ecdysis, the final step that frees the body from the old shell. These include collapse of the second instar trachea, filling of the third instar trachea, locomotor stopping, “biting behavior,” in which the larva appears to tear at the old cuticle, and then ecdysis. These stages are controlled by three neuropeptides, ecdysis triggering hormone (ETH), eclosion hormone (EH), and crustacean cardioactive peptide (CCAP), released by a handful of neurons. Although much of what we know about ecdysis behavior arises from work in the moth, this week Clark et al. examine larval ecdysis in Drosophila. They used behavioral and immunological observations in wild-type flies and those lacking neurons that release EH, CCAP, or both to examine neuropeptide regulation. Their results suggest an unexpected redundancy in the roles of EH and CCAP, and that the three peptides do not act in a simple linear cascade.
Neurobiology of Disease
Heparin Treatment and Alzheimer Mice
Luigi Bergamaschini, Emanuela Rossi, Claudio Storini, Simone Pizzimenti, Maria Distaso, Carlo Perego, Ada De Luigi, Carlo Vergani, and Maria Grazia De Simoni
(see pages 4181-4186)
Several recent publications have tested potential therapeutic strategies for clearing of β-amyloid (Aβ) protein-containing plaques. Aβ may influence disease progression by several mechanisms, including its proinflammatory properties. In this issue Bergamaschini et al. report that low molecular weight heparin, an anticoagulant in common clinical use, can reduce Aβ. Intraperitoneal delivery of enoxaparin (ENO) reduced the number and area of neocortical Aβ plaques in an Alzheimer's disease (AD) mouse (APP23) that overexpresses human amyloid precursor protein. Mice were treated three times weekly from 6 months to 1 year of age, a period in which these mice do not show neurodegeneration or behavioral symptoms. Consistent with a reduction in inflammation, GFAP-positive reactive astrocytes were all but absent in areas around plaques. Despite the promising effects, many questions remain, particularly regarding whether ENO acts in the periphery or in the CNS. However, the proven safety of ENO in humans may warrant its further study in AD.
