Restraint stress and repeated corticotrophin-releasing factor receptor activation in the amygdala both increase amyloid-ß precursor protein and amyloid-ß peptide but have divergent effects on brain-derived neurotrophic factor and pre-synaptic proteins in the prefrontal cortex of rats.

Both environmental stress and anxiety may represent important risk factors for Alzheimer's disease (AD) pathogenesis. Previous studies demonstrate that restraint stress is associated with increased amyloid beta (Aß) and decreased brain-derived neurotrophic factor (BDNF) levels in the brain. Aß deposition, synaptic loss, and neurodegeneration define major hallmarks of AD, and BDNF is responsible for the maintenance of neurons. In contrast to restraint stress, repeated injections of sub-anxiogenic doses of the corticotrophin releasing factor receptor agonist urocortin1 (Ucn1) administered in the basolateral amygdala (BLA) of rats elicits persistent anxiety-like responses. We hypothesized that both restraint stress and Ucn1-induced anxiety would contribute to a neurobiological abnormality that would change the levels of Aß precursor protein (APP) and Aß as well as BDNF and pre-synaptic markers. In the first experiment, adult male Wister rats (n=5) were subjected to 3-h restraint, as compared to unstressed controls. In the second experiment, adult male Wistar rats (n=6) were subjected to sub-anxiogenic doses of Ucn1 (6 fmol/100 nl) administered in the BLA for 5 consecutive days, as compared to controls. Following each respective treatment, the social interaction (SI) test was performed to measure anxiety-like behavior. Protein studies were then conducted to quantify levels of APP, Aß, BDNF and presynaptic proteins in the prefrontal cortex (PFC). In both experiments, we detected differences in either corticosterone levels or the SI test associated with a stress response. Furthermore, our findings indicate that both restraint stress and Ucn1 administration in the BLA lead to increased APP and Aß deposition. However, restraint-induced stress leads to reductions in the levels of BDNF and presynaptic markers, while Ucn1-induced anxiety is associated with increases in the levels of each respective protein. This demonstrates a convergent role for stress response and Ucn1-induced anxiety in the regulation of APP and Aß, but opposing roles for each respective treatment in the regulation of BDNF and presynaptic markers.

Restricting medicaid payments for transportation: effects on inner-city patients' health care.

BACKGROUND: Prior approval programs have been used to control spiraling costs of Medicaid, but they are rarely formally assessed. We evaluated the effect of a change in Indiana Medicaid's policy (effective October 1, 1993) requiring prior approval to pay transportation costs. METHODS: We performed a historical cohort study comparing the health care utilization of Medicaid patients during the first 6 months of 1993 versus the first 6 months of 1994. Subjects included all Medicaid patients who visited any inpatient or outpatient site affiliated with an inner-city public hospital in the first 6 months of 1993 (N = 23,015) and 1994 (N = 23,707). RESULTS: These Medicaid patients made 82,961 visits in the first 6 months of 1993 and 79,809 visits in the first 6 months of 1994. Visits to hospital-based primary care clinics declined 16% (P < 0.001), which was partially offset by a 7% increase in visits to neighborhood health centers (P < or = 0.001). Emergency and urgent visits fell by 8%; visits for medication refills fell by 18% (P < 0.001 for each). Hospitalizations increased slightly in 1994, with no change in the number of inpatient days. There was no change in inpatient or outpatient nontransportation charges. There were no systematic reductions in selected aspects of preventive care. However, there were fewer emergency and urgent visits among patients with reactive airway disease. CONCLUSIONS: Requiring prior approval for transportation was associated with reductions in visits for primary care visits and refilling prescriptions without measurable short-term effects on charges or selected clinical parameters. Neighborhood health centers partially ameliorated the decline in primary care visits.