Nicotine increases eclampsia-like seizure threshold and attenuates microglial activity in rat hippocampus through the α7 nicotinic acetylcholine receptor.

OBJECTIVE: A considerable number of studies have demonstrated that nicotine, a α7-nicotinic acetylcholine receptor (α7-nAChR) agonist, can dampen immune response through the cholinergic anti-inflammatory pathway. Evidence suggests that inflammation plays a critical role in eclampsia, which contributes to maternal and fetal morbidity and mortality. In the present study, possible anti-inflammation and neuro-protective effects of nicotine via α7-nAChRs have been investigated after inducing eclampsia-like seizures in rats. METHODS: Rat eclampsia-like models were established by administering lipopolysaccharide (LPS) plus pentylenetetrazol (PTZ) in pregnant rats. Rats were given nicotine from gestation day (GD) 14-19. Then, clinical symptoms were detected. Seizure severity was recorded by behavioral tests, serum levels of inflammatory cytokines were measured by Luminex assays, microglia and astrocyte expressions were detected by immunofluorescence, and changes in neuronal number in the hippocampal CA1 region among different groups were detected by Nissl staining. RESULTS: Our results revealed that nicotine effectively improved fetal outcomes. Furthermore, it significantly decreased systolic blood pressure, and maternal serum levels of Th1 cytokines (TNF-α, IL-1ß, IL-6 and IL-12P70) and an IL-17 cytokine (IL-17A), and dramatically increased eclampsia-like seizure threshold. Moreover, this attenuated neuronal loss and decreased the expression of microglial activation markers of the hippocampal CA1 region in the eclampsia-like group. Additionally, pretreatment with α-bungarotoxin, a selective α7-nAChR antagonist could prevent the protective effects of nicotine in eclampsia-like model rats. CONCLUSION: Our findings indicate that the administration of nicotine may attenuate microglial activity and increase eclampsia-like seizure threshold in rat hippocampus through the α7 nicotinic receptor.

Visually guided reaching: bilateral posterior parietal lesions cause a switch from fast visuomotor to slow cognitive control.

The visually guided reaching of two patients with bilateral optic ataxia was explored in two experiments. In Experiment 1 simple delayed pointing was compared with immediate pointing. In the immediate pointing task both variable and constant errors increased with target eccentricity. In contrast to the performance of control subjects and contrary to their own beliefs, the patients both showed improved accuracy in the delay condition. This improvement was manifest as a reduction in both pointing variability and in the constant angular error towards the point of fixation. Both angular errors and their improvement with the delay were proportional to target eccentricity. Experiment 2 used a task in which the target was pre-viewed 5s prior to its re-exposure for pointing ('delayed real pointing'). On some trials a conflict was introduced between the present and previous visual information by changing the target's location during the delay. In contrast to control subjects, who ignored the pre-viewed location and aimed directly at the current target, both patients with optic ataxia initiated their movements towards the previously viewed target location. Evidently they relied on off-line information in preference to on-line visual information. In addition, the patients often failed to detect the changes in target location. One of the patients sometimes even guessed incorrectly that the target had changed its location, and her movement trajectory was then more affected by her false belief than by the target's actual location. These findings confirm that posterior parietal lesions severely disrupt direct visuomotor transformations, and suggest that the residual performance is mediated indirectly by expectations or beliefs about target position.