Helicobacter pylori filtrate impairs spatial learning and memory in rats and increases β-amyloid by enhancing expression of presenilin-2

Abstract

Helicobacter pylori (H. pylori) infection is related with a high risk of Alzheimer's disease (AD), but the intrinsic link between H. pylori infection and AD development is still missing. In the present study, we explored the effect of H. pylori infection on cognitive function and β-amyloid production in rats. We found that intraperitoneal injection of H. pylori filtrate induced spatial learning and memory deficit in rats with a simultaneous retarded dendritic spine maturation in hippocampus. Injection of H. pylori filtrate significantly increased Aβ42 both in the hippocampus and cortex, together with an increased level of presenilin-2 (PS-2), one key component of γ-secretase involved in Aβ production. Incubation of H. pylori filtrate with N2a cells which over-express amyloid precursor protein (APP) also resulted in increased PS-2 expression and Aβ42 overproduction. Injection of Escherichia coli (E.coli) filtrate, another common intestinal bacterium, had no effect on cognitive function in rats and Aβ production in rats and cells. These data suggest a specific effect of H. pylori on cognition and Aβ production. We conclude that soluble surface fractions of H. pylori may promote Aβ42 formation by enhancing the activity of γ-secretase, thus induce cognitive impairment through interrupting the synaptic function.

Response to comment: ‘Association between Helicobacter pylori burden and Alzheimer's disease’

“…We agree with Kountouras's hypothesis that H. pylori contributes to AD by sharing homologous epitopes with nerve components, thereby triggering autoimmune insults to brain neurons, and finally resulting in AD [5]. A recent study further links H. pylori infection with AD pathologies and suggests that intraperitoneal injection of H. pylori filtrate can promote Ab42 production by enhancing c-secretase and subsequently impairing cognitive performance in a rat model [6]. These studies suggest that autoimmune reactions to brain components might contribute to AD.…”

Extragastric Diseases and Helicobacter pylori

“…Wang et al. demonstrated that injection of H. pylori but not Escherichia coli filtrates induces spatial learning and memory deficit in rats and increases Aβ 42 both in the hippocampus and in the cortex, by enhancing the activity of γ‐secretase, thereby inducing cognitive impairment via an interruption of the synaptic function. These authors also investigated the effect of H. pylori on tau phosphorylation and showed that H. pylori filtrates induce tau hyperphosphorylation at several AD‐related tau phosphorylation sites in rat brains with glycogen synthase kinase‐3β (GSK‐3β) activation.…”

“…In this regard, Baudron et al [31], by investigating the impact of H. pylori infection on the brain of non-Alzheimer's disease (AD) predisposed mice, showed that H. pylori strain SS1 and Helicobacter felis infection induce gastric inflammation compared to noninfected mice, but without induction of brain neuroinflammation or amyloid-b (Ab) deposition. Wang et al [32] demonstrated that injection of H. pylori but not Escherichia coli filtrates induces spatial learning and memory deficit in rats and increases Ab 42 both in the hippocampus and in the cortex, by enhancing the activity of c-secretase, thereby inducing cognitive impairment via an interruption of the synaptic function. These authors also investigated the effect of H. pylori on tau phosphorylation and showed that H. pylori filtrates induce tau hyperphosphorylation at several AD-related tau phosphorylation sites in rat brains with glycogen synthase kinase-3b (GSK-3b) activation.…”

Association between Helicobacter pylori burden and Alzheimer's disease

“…Consistent associations with the Greek data were consequently shown in studies from France and in two large-scale epidemiological studies from the USA (one mentioned by the authors [1]) [5], supporting a role for Hp-I in AD pathobiology. In this respect, recent experimental data indicate that intraperitoneal injection of Hp filtrate, but not Escherichia coli, increases Ab42 production by enhancing the activity of c-secretase, thereby inducing cognitive impairment through interrupting the synaptic function [6].…”