Intermittent Fasting Applied in Combination with Rotenone Treatment Exacerbates Dopamine Neurons Degeneration in Mice

Abstract

Intermittent fasting (IF) was suggested to be a powerful nutritional strategy to prevent the onset of age-related neurodegenerative diseases associated with compromised brain bioenergetics. Whether the application of IF in combination with a mitochondrial insult could buffer the neurodegenerative process has never been explored yet. Herein, we defined the effects of IF in C57BL/6J mice treated once per 24 h with rotenone (Rot) for 28 days. Rot is a neurotoxin that inhibits the mitochondrial complex I and causes dopamine neurons degeneration, thus reproducing the neurodegenerative process observed in Parkinson’s disease (PD). IF (24 h alternate-day fasting) was applied alone or in concomitance with Rot treatment (Rot/IF). IF and Rot/IF groups showed the same degree of weight loss when compared to control and Rot groups. An accelerating rotarod test revealed that only Rot/IF mice have a decreased ability to sustain the test at the higher speeds. Rot/IF group showed a more marked decrease of dopaminergic neurons and increase in alpha-synuclein (α-syn) accumulation with respect to Rot group in the substantia nigra (SN). Through lipidomics and metabolomics analyses, we found that in the SN of Rot/IF mice a significant elevation of excitatory amino acids, inflammatory lysophospholipids and sphingolipids occurred. Collectively, our data suggest that, when applied in combination with neurotoxin exposure, IF does not exert neuroprotective effects but rather exacerbate neuronal death by increasing the levels of excitatory amino acids and inflammatory lipids in association with altered brain membrane composition.

Intermittent fasting causes metabolic stress and leucopenia in young mice

“…Probably such pattern reflects develop ment of late stress situation resulting in exhausting easy available carbohydrate resources such as glucose or glycogen. Levels of TAG in our experiments also well corresponded to literature [31], but no difference on TAG level was found in the fasted group relatively to controls. A decrease in cholesterol levels (Fig.…”

Time-controlled fasting prevents aging-like mitochondrial changes induced by persistent dietary fat overload in skeletal muscle

“…It was conceivable that alternating protracted fasting periods to HFD may have favorable effects on body and SkM metabolism. It has been reported that in rodents IF slightly reduces body weight, affects mitochondrial bioenergetics and causes redox imbalance in a tissue-specific manner [ 31 , 32 ]. However, no differences in mitochondrial bioenergetics or redox homeostasis were observed upon this dietary intervention in SkM [ 31 ].…”

TMEM16A Inhibition Preserves Blood–Brain Barrier Integrity After Ischemic Stroke

“…The rotarod test was used to assess motor deficit and sensorimotor coordination (Tatulli et al, 2018). The mice were trained for 3 days before MCAO using a rotarod device (RWD Life Science, Shenzhen, China).…”