High doses of vitamin E improve mitochondrial dysfunction in rat hippocampus and frontal cortex upon aging

Abstract

Rat aging from 4 to 12 mo was accompanied by hippocampus and frontal cortex mitochondrial dysfunction, with decreases of 23 to 53% in tissue and mitochondrial respiration and in the activities of complexes I and IV and of mitochondrial nitric oxide synthase (mtNOS) (P < 0.02). In aged rats, the two brain areas showed mitochondria with higher content (35-78%) of oxidation products of phospholipids and proteins and with higher (59-95%) rates of O(2)(-) and H(2)O(2) production (P < 0.02). Dietary supplementation with vitamin E (2.0 or 5.0 g/kg of food) from 9 to 12 mo of rat age, restored in a dose-dependent manner, the decreases in tissue and mitochondrial respiration (to 90-96%) and complexes I and IV and mtNOS activities (to 86-88%) of the values of 4-mo-old rats (P < 0.02). Vitamin E prevented, by 73-80%, the increases in oxidation products, and by 62-68%, the increases in O(2)(-) and H(2)O(2) production (P < 0.05). High resolution histochemistry of cytochrome oxidase in the hippocampal CA1 region showed higher staining in vitamin E-treated rats than in control animals. Aging decreased (19%) hippocampus mitochondrial mass, an effect that was restored by vitamin E. High doses of vitamin E seem to sustain mitochondrial biogenesis in synaptic areas.

Effects of Long-Term Rice Bran Extract Supplementation on Survival, Cognition and Brain Mitochondrial Function in Aged NMRI Mice

“…Additionally, mRNA expression of respiratory system complexes I and IV as well as protein expression of complexes I, IV and V was numerically or significantly decreased which might contribute to impaired mitochondrial respiration in the brains of aged NMRI mice. Our findings about impaired brain mitochondrial function in aged mice very well match existing literature data about brain mitochondrial dysfunction in aged mice (Afshordel et al 2015;Navarro et al 2002Navarro et al , 2005Navarro et al , 2011 as recently discussed in detail (Hagl et al 2016). We additionally found that mRNA and protein expression of proteins associated with fission and fusion processes were changed in aged NMRI mice.…”

“…Similarly, RBE administration to young guinea pigs ameliorated brain mitochondrial function by increasing mitochondrial content and by protecting cells from nitrosative stress (Hagl et al 2013). Navarro and coworkers reported that a-tocopherol, which is a key component of RBE, increased brain mitochondrial function (respiration, ATP production, mitochondrial content) in aging rats (Navarro et al 2011) and mice (Navarro et al 2005).…”

Mitochondrial Energy Metabolism and Redox Signaling in Brain Aging and Neurodegeneration

“…Although not free of discrepancy (236), multiple studies have shown the occurrence of a mitochondrial nitric oxide synthase (mtNOS) in several tissues [including brain (233) and with a function in rat brain development (200)] by its biochemical activity and by the inhibition of mitochondrial respiration elicited by NOS substrates and inhibitors (167,171,172). Mitochondrial metabolic states regulate the diffusion of both$NO and H 2 O 2 from mitochondria to cytosol (32,200).…”

Chronic α-Tocopherol Increases Central Monoamines Synthesis and Improves Cognitive and Motor Abilities in Old Rats

“…44,66,73 In this regard, vitamin E deficiency has been associated with cognitive and motor impairments 43 67,75 and reducing the degeneration of hippocampal cells. 76 Moreover, the antioxidant efficiency of vitamin E is increased after long-term treatments with α-tocopherol because brain tend to increase its concentration (within the lipid bilayer of membranes) 26 in a doseresponse manner, as observed in this work and reported previously.…”