Mitochondrial Ferritin Deletion Exacerbates β‐Amyloid‐Induced Neurotoxicity in Mice

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.

Induction of the Vitamin D Receptor Attenuates Autophagy Dysfunction-Mediated Cell Death Following Traumatic Brain Injury

“…Nuclei were counterstained with DAPI. The number of TUNEL-DAPI positive cells was counted as described previously [19]. The counting area was located in the same position in all groups.…”

TRPC1 Deficiency Exacerbates Cerebral Ischemia/Reperfusion-Induced Neurological Injury by Potentiating Nox4-Derived Reactive Oxygen Species Generation

“…The memory deficits and spatial learning of mice were examined using the Morris water maze as previously described [18,19]. The experimental apparatus (diameter = 120 cm, height = 50 cm) was divided into four quadrants, filled with water, and maintained at 25°C.…”

MicroRNA-107 prevents amyloid-β-induced neurotoxicity and memory impairment in mice

“…APP/PS mice exhibit typical Ad phenotypes, including the impairment of memory and hippocampal long-term potentiation (LTP), loss of pyramidal cells and accumulation of Aβ; however, these symptoms usually appear in mice at a late stage (>6 months of age) (4). Aβ injections induce neurotoxicity and this may be a novel method of inducing Ad in mice, enabling further research to be performed; cell death in mice with a typical Ad phenotype has been observed in a short period of time following injection of Aβ (6,7).…”

“…It has been demonstrated that miR-107 expression is downregulated in the temporal cortical grey matter during the early phases of Ad (17,18). Furthermore, accumulation of Aβ in the brain serves an important role in the pathogenesis of Ad (6). It has been reported that miRNAs regulate multiple aspects of Ad development and progression, indicating that targeting miRNAs may be a novel strategy of treating Ad (15,16).…”