Sex-dependent Actions of Amyloid Beta Peptides on Hippocampal Choline Carriers of Postnatal Rats

Abstract

It is suggested that amyloid beta peptides (Abeta) play a role in the pathogenesis of Alzheimer disease but their physiological function is still unknown. However, low pM-nM concentrations mediate a hypofunction of a basal forebrain cholinergic system without marked signs of neurotoxicity. In this study, we compared in vitro effects of soluble nonaggregated human Abeta 1-40 and 1-42 either on synaptosomal hemicholinium-3 sensitive choline carriers or on membrane fluidity in hippocampi of male and female Wistar rats aged 7 and 14 days or 2-3 months. The results indicate age- and sex-dependent effects mediated by peptides at nM concentrations but no significant differences between both fragments. Namely, opposite actions were observed in 14-day (the increase in the choline uptake and membrane fluidity) when compared to 7-day old and adult males (the mild drops). Lineweaver-Burk plot analysis revealed that the enhancement of the high-affinity choline transport in 14-day old males occurs via alterations in K (M )and the change was accompanied by a mild increase in the specific binding of [3H]hemicholinium-3. On the other hand, no age-dependent differences were found in females. Rat Abeta 1-40 mediated similar effects on 14-day old rats as the corresponding human fragment. Moreover, higher levels of soluble peptides were detected in immature when compared to mature male brains by means of competitive ELISA. Our study indicates that Abeta could play a role in postnatal sexual differentiation of hippocampal cholinergic system.

Complex of Amyloid β Peptides with 24-Hydroxycholesterol and Its Effect on Hemicholinium-3 Sensitive Carriers

“…High concentrations (100 lg/ml) of monomeric randomly structured Ab 1-42 also increase DPH anisotropy of highly depleted planar lipid bilayers probably via stabilization of local headgroup-headgroup interactions [40]. Nevertheless, our results support the studies reporting Ab-mediated cholesterol-dependent effects on DPH anisotropy [24] and are in accordance with our recent work performed on synaptosomes of immature male rats [41]. Moreover, a question arises whether DPH really intercalates between the acyl chains of fatty acids in hydrocarbon core of cholesterol depleted membranes.…”

Near‐complete adaptation of the PRiMA knockout to the lack of central acetylcholinesterase

“…High-affinity choline uptake was determined as previously described (Kristofiková et al 2006). We added 100 lL of synaptosomal suspension to 800 lL of Krebs-Ringer-HEPES-glucose buffer (128 mM NaCl, 5 mM KCl, 2.7 mM CaCl 2 , 1.2 mM MgSO 4 , 5 mM glucose and 10 mM HEPES, pH 7.4) and incubated the mixture for 4 min at 37°C.…”

Sex effect on presenilins expression in post-natal rat brain

“…Similar sex-dependent differences in PSEN1 gene expression were observed in the hippocampus limitedly to the first post-natal week, while no differences were observed in the mature brain. Kristofikova and colleagues also described a sex-dependent dimorphism during post-natal hippocampal development regarding the action of Aβ peptides on choline carriers in the rat brain, suggesting a role for the Aβ in the postnatal sexual differentiation of the hippocampal cholinergic system [31]. With regard to the quantitative expression profile of PSENs during post-natal life, we find a relatively high expression of PSEN1 transcripts at P0 in cerebral cortex and hippocampus in both sexes that steadily decreased during the period of synaptogenesis in early post-natal development.…”