The consolidation of newly formed memories and their retrieval are energetically demanding processes. Aerobic glycolysis (AG), also known as the Warburg effect, consists of the production of lactate from glucose in the presence of oxygen. The astrocyte neuron lactate shuttle hypothesis posits that astrocytes process glucose by AG to generate lactate, which is used as a fuel source within neurons to maintain synaptic activity. Studies in mice have demonstrated that lactate transport between astrocytes and neurons is required for long-term memory formation, yet the role of lactate production in memory acquisition and retrieval has not previously been explored. Here, we examined the effect of dichloroacetate (DCA), a chemical inhibitor of lactate production, on spatial learning and memory in mice using the Morris water maze (MWM).In vivohyperpolarized13C-pyruvate magnetic resonance spectroscopy revealed decreased conversion of pyruvate to lactate in the mouse brain following DCA administration, concomitant with a reduction in the phosphorylation of pyruvate dehydrogenase. DCA exposure before each training session in the MWM impaired learning, which subsequently resulted in impaired memory during the probe trial. In contrast, mice that underwent training without DCA exposure, but received a single DCA injection before the probe trial exhibited normal memory. Our findings indicate that AG plays a key role during memory acquisition but is less important for the retrieval of established memories. Thus, the activation of AG may be important for learning-dependent synaptic plasticity rather than the activation of signaling cascades required for memory retrieval.
29 October 2012 in Contrast Media & Molecular Imaging
We have used fast-ion-beam laser spectroscopy to measure the 1s2s-1s2 intervals in Be iii to an absolute accuracy of 1 part in . Our results are (in ): σ(1s2 -1s2 =28 864.6120(4), σ(1s2 1s2 =26 853.0534(3), σ(1s2 1s2 ) =26 867.9484(3). These results are an improvement over previous measurements by nearly 3 orders of magnitude and show evidence of uncalculated O( ) relativistic corrections. Once those terms are computed, our measurement will allow QED calculations in two-electron atoms to be tested at the 100 ppm level.
7 December 2012 in Journal of Materials Chemistry B
Polymer cross-linking was explored as an approach for increasing the relaxivity of macromolecular contrast agents for magnetic resonance imaging. Poly(ethylene glycol) methyl ether methacrylate, N-(2-aminoethyl)methacrylamide hydrochloride, and the cross-linker ethylene glycol dimethacrylate were copolymerized under free radical conditions. By tuning the cross-linker content and reaction concentration, it was possible to obtain 10 nm nanogels in a single synthetic step. The pendant amine moieties were functionalized with an isothiocyanate derivative of diethylenetriaminepentaacetic acid (DTPA) and Gd(III) was chelated. In comparison with a linear control polymer prepared under the same conditions in the absence of the cross-linking agent, the nanogel contrast agent did exhibit enhanced relaxivity with an r1 of 20.8 ± 0.2 at 20 MHz and 17.5 ± 0.4 at 60 MHz (corresponding to the clinical field strength of 1.5 T). The nuclear magnetic resonance dispersion profile was modeled to demonstrate that the enhanced relaxivity was a result of the nanogel agent's increased rotational correlation time, that is proposed to result from the constraint on motion imparted by the cross-linking. T1 weighted imaging in mice showed enhanced contrast and vascular circulation for the nanogel relative to Gd(III)–DTPA (Magnevist) demonstrating the future promise of these new agents.