The macrocyclic lactones ivermectin and moxidectin show differential effects on rotational behavior in the 6-hydroxydopamine mouse model of Parkinson's disease.

Parkinson's disease (PD) is a common neurodegenerative disease characterized by motor and cognitive deficits, the result of dopamine (DA)-depletion within the basal ganglia. Currently, DA replacement therapy in the form of Sinemet (L-DOPA plus Carbidopa) provides symptomatic motor benefits and remains the "gold standard" for treatment. Several pharmacological approaches can enhance DA neurotransmission including the administration of DA receptor agonists, the inhibition of DA metabolism, and enhancing pre-synaptic DA release. DA neurotransmission is regulated by several receptor subtypes including signaling through the purinergic system. P2 × 4 receptors (P2 × 4Rs) are a class of cation-permeable ligand-gated ion channels activated by the synaptic release of extracellular adenosine 5'-triphosphate (ATP). P2 × 4Rs are expressed throughout the central nervous system including the dopaminergic circuitry of the substantia nigra, basal ganglia, and related reward networks. Previous studies have demonstrated that P2 × 4Rs can modulate several DA-dependent characteristics including motor, cognitive, and reward behaviors. Ivermectin (IVM) and moxidectin (MOX) are two macrocyclic lactones that can potentiate P2 × 4Rs. In this study, we sought to investigate the role of P2 × 4Rs in mediating DA neurotransmission by exploring their impact on DA-dependent behavior, specifically rotation frequency in the unilateral 6-hydroxydopamine-lesioned mouse model of DA-depletion. While we did not observe any differences in the degree of lesioning based on immunostaining for tyrosine hydroxylase between sexes, male mice displayed a greater number of rotations with L-DOPA compared to female mice. In contrast, we observed that IVM plus L-DOPA increased the number of rotations (per 10 min) in female, but not male mice. These findings highlight the potential role of pharmacologically targeting the purinergic receptor system in modulating DA neurotransmission as well as the importance of sex differences impacting outcome measures.

Runoff losses of suspended sediment, nitrogen, and phosphorus from a small watershed in Korea.

Nutrients and sediments in runoff lead to the degradation of water quality of lakes and streams. The development of schemes to mitigate such degradation requires a characterization of the underlying transport processes. The objectives of this study were to develop annual and seasonal load-discharge relationships for suspended sediment (SS), total nitrogen (TN), and total phosphorus (TP) losses from a small mixed land use watershed and to use these relationships to explicate the annual and monthly patterns of losses of these species. Data from 1996 to 2004 were used to develop load-discharge relationships for SS, TN, and TP at the HP#6 watershed, a subwatershed of the Balhan reservoir watershed located in Bongdam-myun and Paltan-myun, Gyeonggi-do, Korea. Standard least squares curve fitting and S-estimation procedures were used to fit power functions to the data collected over this time period. The fitted load-discharge relationships are indicative of seasonal variations in SS and TN and of TP losses from HP#6. The exponents of the fitted power functions for TN and TP in the fall, for TP in summer season, and for SS in all seasons are >1, indicating that the concentrations of these species increase as flow rate increases. Most of the SS, TN, and TP transported in runoff left the watershed between April and September; thus, cost-efficient strategies can be established by focusing on this period. Further study of the seasonal variations is required for a better characterization of seasonal losses of SS, TN, and TP in runoff from the HP#6 watershed.