Abstract
Mitochondrial ferritin (FtMt) is a mitochondrial iron storage protein which protects mitochondria from iron-induced oxidative damage. Our previous studies indicate that FtMt attenuates β-amyloid- and 6-hydroxydopamine-induced neurotoxicity in SH-SY5Y cells. To explore the protective effects of FtMt on β-amyloid-induced memory impairment and neuronal apoptosis and the mechanisms involved, 10-month-old wild-type and Ftmt knockout mice were infused intracerebroventricularly (ICV) with Aβ25–35 to establish an Alzheimer's disease model. Knockout of Ftmt significantly exacerbated Aβ25–35-induced learning and memory impairment. The Bcl-2/Bax ratio in mouse hippocampi was decreased and the levels of cleaved caspase-3 and PARP were increased. The number of neuronal cells undergoing apoptosis in the hippocampus was also increased in Ftmt knockout mice. In addition, the levels of L-ferritin and FPN1 in the hippocampus were raised, and the expression of TfR1 was decreased. Increased MDA levels were also detected in Ftmt knockout mice treated with Aβ25–35. In conclusion, this study demonstrated that the neurological impairment induced by Aβ25–35 was exacerbated in Ftmt knockout mice and that this may relate to increased levels of oxidative stress.
Highlights
Alzheimer’s disease (AD) is a multifaceted neurodegenerative disease of the elderly which is characterized by neuronal loss, neuroinflammation, and progressive memory and cognitive impairment [1]
The time spent in the target quadrant in the probe trial was less in both the wild-type mice (WT) + Aβ25–35 and the knockout mice (KO) + Aβ25–35 groups than in the control groups
The KO + Aβ25–35 group was in the target quadrant for even less time than the WT + Aβ25–35 group (Figure 1(d))
Summary
Alzheimer’s disease (AD) is a multifaceted neurodegenerative disease of the elderly which is characterized by neuronal loss, neuroinflammation, and progressive memory and cognitive impairment [1]. Aβ is considered to be a major factor in the pathophysiological mechanisms underlying AD and has been shown to directly induce neuronal cell death [3]. Aβ is a useful tool for establishing AD models and investigating the mechanisms involved in AD pathogenesis [4]. Single administration of Aβ25–35 into the lateral ventricles of mice or rats impairs memory and induces neurodegeneration in the hippocampus [6,7,8,9,10]. We have previously shown that Aβ25–35, like Aβ1–42, exerted neurotoxic effects on SH-SY5Y cells [11]. These data are among numerous studies confirming that Aβ25–35 is a useful tool for investigating AD-related mechanisms in animal models [10]
Sign-in/Register to view highlights & summary Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a callDisclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.
