Neuroscience
-
Data from our laboratory indicate that the orexin system is involved in the regulation of both conditioned and unconditioned responding for palatable foods. Anticipation of food rewards activates orexin receptor containing neurons within the paraventricular nucleus of the thalamus (PVT). The PVT regulates mesolimbic dopamine neurochemistry through direct connections with the nucleus accumbens and modulates the processing of cognitive-emotional information, suggesting that the PVT may represent a unique brain region with the capacity to mediate orexinergic effects on brain dopamine and behavior. ⋯ Data from these studies indicate that orexin-A action in the PVT increases dopamine levels in the nucleus accumbens. In addition, endogenous orexin signaling in the PVT mediates locomotor activity and hedonic feeding responses. Together these data highlight the PVT as a critical site capable of mediating orexin action on brain dopamine and reward-based feeding.
-
The cerebellar uvula (lobule IX), a part of the vestibulocerebellum, is extensively connected to the areas of the brainstem that participate in cardiovascular regulation and vestibular signal processing. This suggests that the uvula regulates blood pressure (BP) during postural alterations. Previous studies showed that lesions of the uvula affected the baroreceptor reflex and cardiovascular responses during postural alterations. ⋯ By contrast, photoinhibition had no statistically significant effect on BP recovery during head-up tilts. The effects of photoinhibition on BP during tilts were significantly different from those observed during the resting condition, indicating that cerebellar control of BP during tilts is dynamic rather than static. Taken together, these results suggest that PCs in the uvula dynamically regulates BP maintenance during postural alterations.
-
Apolipoprotein (apo) E4 isoform, a major risk factor for Alzheimer disease (AD), is more susceptible to proteolysis than apoE2 and apoE3 isoforms. ApoE4 fragments have been found in AD patients' brain. In the present study, we examined the effect of full-length apoE4 and apoE4 fragments apoE4[Δ(186-299)] and apoE4[Δ(166-299)] on inflammation in human neuroblastoma SK-N-SH and human astrocytoma SW-1783 cells. ⋯ Additionally, apoE4[Δ(186-299)] leads to decreased IL-10 gene expression in SK-N-SH cells, whereas both apoE4 and apoE4[Δ(186-299)] lead to decreased TNFα gene expression without affecting IL-1β and IL-10 gene expression in SW-1783 cells. Overall, our findings indicate that a specific apoE4 fragment (apoE4[Δ(186-299)]), with molecular mass similar that of apoE4 fragments detected in AD patients' brain, can influence the level of inflammatory molecules in brain cell lines. It is possible that these phenomena contribute to AD pathogenesis.
-
We have previously reported that experimental mild traumatic brain injury results in increased sensitivity to stressful events during the first post-injury weeks, as determined by analyzing the hypothalamic-pituitary-adrenal (HPA) axis regulation following restraint-induced stress. This is the same time period when rehabilitative exercise has proven to be ineffective after a mild fluid-percussion injury (FPI). Here we evaluated effects of stress on neuroplasticity. ⋯ A suppression of MR was found at PID 1 in vehicle-treated FPI and Sham groups. Decreases in the precursor form of BDNF were observed in different FPI groups at PIDs 7 and 14. These findings suggest that the increased sensitivity to stressful events during the first post-injury weeks, after a mild FPI, has an impact on hippocampal neuroplasticity.
-
Patients with homonymous hemianopia often show a contralesional shift towards their blind field when bisecting horizontal lines ('hemianopic line bisection error', HLBE). The reasons for this spatial bias are not well understood and debated. Eccentric fixation and adaptive orienting of eye movements towards the blind field have been suggested as hypothetical explanations but were not tested experimentally yet. ⋯ Finally, the size of the saccadic search field in the scotoma was not significantly correlated to the HLBE in hemianopia. We conclude that eccentric fixation, contralesional hyperattention or ipsilesional hypoattention, or good or poor oculomotor compensation of the field loss itself are not likely causes of the HLBE in chronic homonymous hemianopia. Implications of these findings and alternative explanations are discussed.