ABSTRACT
AIMS: To explore the novel linkage between a Western diet combining high saturated fat, sugar, and salt (HFSS) and neurological dysfunctions during aging as well as Metformin intervention, we assessed cerebral cortex abnormalities associated with sensory and motor dysfunctions and cellular and molecular insights in brains using HFSS-fed mice during aging. We also explored the effect of Metformin treatment on these mice. METHODS: C57BL/6 mice were fed with HFSS and treated with metformin from 20 to 22 months of age, resembling human aging from 56 to 68 years of age (an entry phase of the aged portion of lifespan). RESULTS: The motor and sensory cortexes in mice during aging after HFSS diet showed: (A) decreased motor-muscular and sensory functions; (B) reduced inflammation-resolving Arg-1+ microglia; (C) increased inflammatory iNOs+ microglia and TNFα levels; (D) enhanced abundance of amyloid-ß peptide and of phosphorylated Tau. Metformin attenuated these changes. CONCLUSION: A HFSS-combined diet caused motor-muscular and sensory dysfunctions, neuroinflammation, and neurodegeneration, whereas metformin counteracted these effects. Our findings show neuroinflammatory consequences of a HFSS diet in aging. Metformin curbs the HFSS-related neuroinflammation eliciting neuroprotection.
Subject(s)
Aging/drug effects , Diet, Carbohydrate Loading/adverse effects , Diet, High-Fat/adverse effects , Diet, Western/adverse effects , Hypoglycemic Agents/pharmacology , Metformin/pharmacology , Neurodegenerative Diseases/drug therapy , Neuroinflammatory Diseases/drug therapy , Sensorimotor Cortex/drug effects , Sodium Chloride, Dietary/adverse effects , Aged , Aging/pathology , Aging/physiology , Animals , Disease Models, Animal , Humans , Hypoglycemic Agents/administration & dosage , Male , Metformin/administration & dosage , Mice , Mice, Inbred C57BL , Neurodegenerative Diseases/etiology , Neuroinflammatory Diseases/etiology , Sensorimotor Cortex/immunology , Sensorimotor Cortex/pathology , Sensorimotor Cortex/physiopathologyABSTRACT
BACKGROUND: Very early exercise has been reported to exacerbate motor dysfunction; however, its mechanism is largely unknown. OBJECTIVE: This study examined the effect of very early exercise on motor recovery and associated brain damage following intracerebral hemorrhage (ICH) in rats. METHODS: Collagenase solution was injected into the left striatum to induce ICH. Rats were randomly assigned to receive placebo surgery without exercise (SHAM) or ICH without (ICH) or with very early exercise within 24 hours of surgery (ICH+VET). We observed sensorimotor behaviors before surgery, and after surgery preexercise and postexercise. Postexercise brain tissue was collected 27 hours after surgery to investigate the hematoma area, brain edema, and Il1b, Tgfb1, and Igf1 mRNA levels in the striatum and sensorimotor cortex using real-time reverse transcription polymerase chain reaction. NeuN, PSD95, and GFAP protein expression was analyzed by Western blotting. RESULTS: We observed significantly increased skillful sensorimotor impairment in the horizontal ladder test and significantly higher Il1b mRNA levels in the striatum of the ICH+VET group compared with the ICH group. NeuN protein expression was significantly reduced in both brain regions of the ICH+VET group compared with the SHAM group. CONCLUSION: Our results suggest that very early exercise may be associated with an exacerbation of motor dysfunction because of increased neuronal death and region-specific changes in inflammatory factors. These results indicate that implementing exercise within 24 hours after ICH should be performed with caution.
