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Bill & Melinda Gates Foundation.

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Repetitive activation of hippocampal mossy fibers evokes a long-term potentiation (LTP) of synaptic responses in pyramidal cells in the CA3 region that is independent of N-methyl-D-aspartate receptor activation. Previous results suggest that the site for both the induction and expression of this form of LTP is presynaptic. Experimental elevation of cyclic adenosine 3',5'-monophosphate (cAMP) both mimics and interferes with tetanus-induced mossy fiber LTP, and blockers of the cAMP cascade block mossy fiber LTP. It is proposed that calcium entry into the presynaptic terminal may activate Ca(2+)-calmodulin-sensitive adenylyl cyclase I which, through protein kinase A, causes a persistent enhancement of evoked glutamate release.

BackgroundTraffic-related particles induce oxidative stress and may exert adverse effects on central nervous system function, which could manifest as cognitive impairment.ObjectiveWe assessed the association between black carbon (BC), a marker of traffic-related air pollution, and cognition in older men.MethodsA total of 680 men (mean ± SD, 71 ± 7 years of age) from the U.S. Department of Veterans Affairs Normative Aging Study completed a battery of seven cognitive tests at least once between 1996 and 2007. We assessed long-term exposure to traffic-related air pollution using a validated spatiotemporal land-use regression model for BC.ResultsThe association between BC and cognition was nonlinear, and we log-transformed BC estimates for all analyses [ln(BC)]. In a multivariable-adjusted model, for each doubling in BC on the natural scale, the odds of having a Mini-Mental State Examination (MMSE) score ≤ 25 was 1.3 times higher [95% confidence interval (CI), 1.1 to 1.6]. In a multivariable-adjusted model for global cognitive function, which combined scores from the remaining six tests, a doubling of BC was associated with a 0.054 SD lower test score (95% CI, −0.103 to −0.006), an effect size similar to that observed with a difference in age of 1.9 years in our data. We found no evidence of heterogeneity by cognitive test. In sensitivity analyses adjusting for past lead exposure, the association with MMSE scores was similar (odds ratio = 1.3; 95% CI, 1.1 to 1.7), but the association with global cognition was somewhat attenuated (−0.038 per doubling in BC; 95% CI, −0.089 to 0.012).ConclusionsAmbient traffic-related air pollution was associated with decreased cognitive function in older men.

In adults, penetrating, moderate, and severe TBIs are associated with cognitive deficits 6 months or longer postinjury. There is insufficient evidence to determine whether mild TBI is associated with cognitive deficits 6 months or longer postinjury.

These data support the hypothesis that exposure to pesticides may increase risk for PD. Future studies should seek to identify the specific chemicals responsible for this association.