Modeling fall propensity in Parkinson's disease: deficits in the attentional control of complex movements in rats with cortical-cholinergic and striatal-dopaminergic deafferentation.

Cognitive symptoms, complex movement deficits, and increased propensity for falls are interrelated and levodopa-unresponsive symptoms in patients with Parkinson's disease (PD). We developed a test system for the assessment of fall propensity in rats and tested the hypothesis that interactions between loss of cortical cholinergic and striatal dopaminergic afferents increase fall propensity. Rats were trained to traverse stationary and rotating rods, placed horizontally or at inclines, and while exposed to distractors. Rats also performed an operant Sustained Attention Task (SAT). Partial cortical cholinergic and/or caudate dopaminergic deafferentation were produced by bilateral infusions of 192 IgG-saporin (SAP) into the basal forebrain and/or 6-hydroxydopamine (6-OHDA) into the caudate nucleus, respectively, modeling the lesions seen in early PD. Rats with dual cholinergic-dopaminergic lesions (DL) fell more frequently than SAP or 6-OHDA rats. Falls in DL rats were associated with incomplete rebalancing after slips and low traversal speed. Ladder rung walking and pasta handling performance did not indicate sensorimotor deficits. SAT performance was impaired in DL and SAP rats; however, SAT performance and falls were correlated only in DL rats. Furthermore, in DL rats, but not in rats with only dopaminergic lesions, the placement and size of dopaminergic lesion correlated significantly with fall rates. The results support the hypothesis that after dual cholinergic-dopaminergic lesions, attentional resources can no longer be recruited to compensate for diminished striatal control of complex movement, thereby "unmasking" impaired striatal control of complex movements and yielding falls.

Sustained attention in mice: expanding the translational utility of the SAT by incorporating the Michigan Controlled Access Response Port (MICARP).

Advances in mouse genetic technology have spurred increasing interest in the development of cognitive tasks for mice. Here, we describe and discuss the modifications necessary to adapt a task for the assessment of sustained attention performance for use in mice, including for taxing the top-down control of such performance. The validity of the Sustained Attention Task (SAT), including the distractor version (dSAT), has previously been demonstrated in rats and humans. This task requires moveable or retractable operanda; insertion of operanda into the operant chambers cues animals to respond to a prior signal or non-signal event, reporting either a hit or a miss, or a correct rejection or false alarm, respectively. Retractable levers did not support sufficiently high and stable levels of performance in mice. Given the widespread use of static nose-poke devices for testing operant performance in mice, we therefore designed and fabricated a retractable nose-poke device. As this device extends into chambers, a hole for nose-poking is slowly opened and closed again as the device retracts (termed the "Michigan Controlled Access Response Port", MICARP). Results describe the effects of variation of signal duration and event rate, trial outcome and trial type probability, effects of mice deprivation levels, and the reliability of SAT and dSAT performance. Mice perform the SAT and dSAT at levels comparable to those observed in rats. This task will be of assistance in expanding the translational usefulness of the SAT and dSAT.

Ascorbic acid: a review of its chemistry and reactivity in relation to a wine environment.

Extensive reviews of research are available on the use of ascorbic acid, and its consequent degradation pathways, in physiological conditions or food matrices. However, very little information can be found for wine-related systems. This review highlights the relevant chemistry and reactivity of ascorbic acid with a focus on its behavior and potential behavior in a wine environment. The review describes the use of ascorbic acid as a complementary antioxidant preservative to sulfur dioxide along with the metal-catalyzed and radical-dependent manner by which it achieves this role. The relevant degradation products of ascorbic acid in aerobic and anaerobic conditions are presented as well as the interaction of these degradation products with sulfur dioxide and other wine-relevant sulfur compounds. Limitations in existing knowledge, especially regarding the crossover between the antioxidant and pro-oxidant roles of ascorbic acid, are identified.