ABSTRACT
AIM: Deficient glutamate reuptake occurs in the cerebral cortex of Huntington's disease (HD) patients and murine models. Here, we examine the effects of partial or complete blockade of glutamate transporters on excitatory postsynaptic currents (EPSCs) of cortical pyramidal neurons (CPNs). METHODS: Whole-cell patch clamp recordings of CPNs in slices from symptomatic R6/2 mice and wild-type (WT) littermates were used to examine the effects of selective or concurrent inhibition of glutamate reuptake transporters. RESULTS: Selective inhibition of the glial glutamate transporter 1 (GLT-1) or the glutamate aspartate transporter (GLAST) produced slight decreases in decay time of evoked EPSCs in CPNs from WT and R6/2 mice with no significant differences between genotypes. In contrast, concurrent inhibition of both transporters with DL-TBOA induced a significant increase in area and decay time and this effect was significantly greater in R6/2 CPNs. Furthermore, full blockade also reduced spontaneous EPSC frequency and exacerbated epileptiform activity in CPNs from symptomatic R6/2 mice. CONCLUSIONS: R6/2 CPNs are more sensitive to glutamate accumulation during full inhibition of both glutamate transporters, and these neurons have homeostatic mechanisms to cope with inhibition of GLT-1 or GLAST by a mechanism that involves upregulation of either transporter when the other is deficient.
Subject(s)
Cerebral Cortex/physiopathology , Disease Models, Animal , Excitatory Amino Acid Transporter 1/antagonists & inhibitors , Excitatory Amino Acid Transporter 2/antagonists & inhibitors , Huntington Disease/physiopathology , Animals , Aspartic Acid/pharmacology , Benzopyrans/pharmacology , Excitatory Amino Acid Transporter 1/physiology , Excitatory Amino Acid Transporter 2/physiology , Excitatory Postsynaptic Potentials/drug effects , Excitatory Postsynaptic Potentials/physiology , Female , Huntington Disease/genetics , Male , Mice , Mice, Transgenic , Organ Culture TechniquesABSTRACT
Low parent engagement is frequently identified as a barrier to effective implementation of family-based childhood obesity prevention and control programs. A more nuanced understanding of factors affecting parent engagement is important for improving implementation and, ultimately, program efficacy. This qualitative study examined factors influencing parent engagement in a family-based childhood obesity prevention and control program. Semistructured interviews informed by the health belief model and the transtheoretical model were conducted with 22 predominantly Latina mothers following the scheduled conclusion of program activities. Spanish- and English-language interviews were transcribed, translated into English (if Spanish), coded, and summarized using established protocols. Differences between parents who attended at least two thirds of program activities and those who did not were examined. There were no significant demographic differences between parents who did and did not complete two thirds of program activities. Findings indicated that differences in parent engagement may be at least partially explained by differences in parental motivations for participating and in barriers and facilitators, such as children's level of support and enthusiasm for the program. Parents were highly satisfied with the program content and the community health workers who delivered the program. This study adds to emergent literature regarding parents' experiences in family-based childhood obesity prevention and control programs. Potential targets for improving program engagement are discussed.
