News tips from The Journal of Neuroscience1. Synaptic Sites of Endocannabinoid Synthesis
Takayuki Yoshida, Masahiro Fukaya, Motokazu Uchigashima, Eriko Miura, Haruyuki Kamiya, Masanobu Kano, and Masahiko Watanabe
The retrograde messenger endocannabinoid 2-arachidonoyl-glycerol (2-AG) is produced in postsynaptic cells only to act on CB1 receptors on presynaptic nerve terminals. In this week's Journal, Yoshida et al. examine--very closely--the subcellular localization of the 2-AG production machinery, diacylglycerol lipase-Š (DAGLŠ). The authors used immunostaining and immunoelectron microscopy to visualize DAGLŠ. Cerebellar Purkinje neurons expressed DAGLŠ predominantly on distal dendritic spiny branchlets, with less expression in more proximal, somatodendritic membrane. Interestingly, DAGLŠ was concentrated at the base of spine necks but was excluded from spine necks and heads. Hippocampal pyramidal cells expressed DAGLŠ in spines as well, but here expression was within spine heads and necks, with little in somatodendritic membrane. In the CA1 subfield, stratum radiatum was more heavily labeled than stratum lacunosummoleculare. See the paper by Katona et al. in the May 24, 2006 issue for more on this topic.
2. Neutralizing NG2 after Spinal Injury
Andrew M. Tan, Mario Colletti, Ann. T. Rorai, J. H. Pate Skene, and Joel M. Levine
Axons trying to regenerate after spinal cord injury face a major obstacle in the form of the glial scar. It's not only figuring out what makes axons grow, but also avoiding things that may inhibit growth, such as myelin-associated growth inhibitors, semaphorins, and chondroitin sulfate proteoglycans (CSPGs). This week, Tan et al. tried to take the proteoglycan NG2 out of action. The authors transected rat spinal cords and then treated the animals with neutralizing or nonneutralizing anti-NG2 monoclonal antibodies (mAbs). Antibodies were infused into the spinal cord over several days from gelfoam pledglets. In rats treated with non-neutralizing mAbs, afferent mechanosensory neuron axons usually stopped within the lesion penumbra and failed to enter the core. Neutralizing mAbs, however, allowed the axons to grow through the core of the glial scar. When the sensory nerve was preconditioned with a lesion to stimulate growth, axons grew well past the glial scar and into the white matter.
3. Top-Down Auditory Map Plasticity
Daniel B. Polley, Elizabeth E. Steinberg, and Michael M. Merzenich
During early critical periods, topographical maps are formed in sensory cortex based on dedicated afferent sensory input, a bottom-up organization. By training rats to respond either to frequency or to intensity of the same auditory stimuli, Polley et al. tested whether auditory rereceptive field plasticity in the adult was also affected by top-down task-dependent factors such as attention. In the authors' protocol, the bottom-up signals remained constant but the top-down focus differed. The proportion of primary auditory cortex (AI) and suprarhinal auditory field (SRAF) dedicated to auditory frequencies in the target range expanded in rats trained in frequency recognition (FR) but not in rats trained in loudness recognition (LR). Conversely, in FR-trained--but not LR-trained--rats, auditory stimuli in the trained decibel range evoked more responses. Perhaps surprising, AI responded as robustly to top-down effects as the SRAF, a "higher" processing center.
4. Refining A‚ Immunotherapy
Marcel Maier, Timothy J. Seabrook, Noel D. Lazo, Liying Jiang, Pritam Das, Christopher Janus, and Cynthia A. Lemere
In a second antibody-based study this week, Maier et al. attempt to refine immunotherapy for Alzheimer's disease (AD). Antibodies raised against A‚1Ė42 have shown some promise in clearing A‚ from brain, but some immunized patients developed signs of meningoencephalitis, possibly caused by a T-cell-mediated immune response. To avoid the immune response, the authors created immunogens that included the N terminus (A‚1Ė15) but not the C-terminal T-cell reactive site. They immunized wild-type mice intranasally with one of four peptides: a lysine-linked tandem repeat of A‚1Ė15; the same peptide linked to a three-amino-acid RGD (Arg-Gly-Asp) cell attachment motif to increase immunogenicity; and each of these coupled to a T1 T-helper cell epitope. These immunogens produced moderate to high antibody titers. Splenocytes collected from immunized mice proliferated upon restimulation with the immunogens but not with full-length A‚. In the AD model hAPPFAD (human amyloid precursor protein, familial AD) mouse, immunization reduced A‚ plaque load and cerebral A‚, and improved cognitive behavior.
Last reviewed: By John M. Grohol, Psy.D. on 30 Apr 2016
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