Intranasal insulin rescues repeated anesthesia-induced deficits in synaptic plasticity and memory and prevents apoptosis in neonatal mice via mTORC1. | LitMetric
Department of Anesthesia and Faculty of Dentistry, McGill University, Montreal, QC, Canada.
Published: July 2021
AI Article Synopsis
Article Abstract
Long-lasting cognitive impairment in juveniles undergoing repeated general anesthesia has been observed in numerous preclinical and clinical studies, yet, the underlying mechanisms remain unknown and no preventive treatment is available. We found that daily intranasal insulin administration to juvenile mice for 7 days prior to repeated isoflurane anesthesia rescues deficits in hippocampus-dependent memory and synaptic plasticity in adulthood. Moreover, intranasal insulin prevented anesthesia-induced apoptosis of hippocampal cells, which is thought to underlie cognitive impairment. Inhibition of the mechanistic target of rapamycin complex 1 (mTORC1), a major intracellular effector of insulin receptor, blocked the beneficial effects of intranasal insulin on anesthesia-induced apoptosis. Consistent with this finding, mice lacking mTORC1 downstream translational repressor 4E-BP2 showed no induction of repeated anesthesia-induced apoptosis. Our study demonstrates that intranasal insulin prevents general anesthesia-induced apoptosis of hippocampal cells, and deficits in synaptic plasticity and memory, and suggests that the rescue effect is mediated via mTORC1/4E-BP2 signaling.
Focal intranasal drug delivery to the olfactory cleft is a promising avenue for pharmaceuticals targeting the brain. However, traditional nasal sprays often fail to deliver enough medication to this specific area. We present a laminar fluid ejection (LFE) method for precise delivery of medications to the olfactory cleft.
* Twenty-one patients and 18 controls underwent pre- and post-insulin cognitive and magnetic resonance spectroscopy (MRS) assessments to measure changes in brain metabolites.
* Results showed that while intranasal insulin increased glutathione levels and improved cognitive performance in healthy participants, it did not have the same effect in individuals with early psychotic disorders.
Objectives: To evaluate the effect of transmucosal glucagon powder (Baqsimi; Amphastar Pharmaceuticals) on blood glucose (BG) concentrations in healthy cats and describe adverse reactions to its administration.
Methods: A randomized, controlled, crossover study was conducted on six healthy cats with a 7-day washout period between treatments. Transmucosal glucagon powder was administered intranasally and rectally and compared with intranasal placebo.
Background: Insulin-like growth factor-1 (IGF-1) promotes neurogenesis, cell survival, and glial function, making it a promising candidate therapy in Alzheimer's disease (AD).
Objective: Long arginine 3-IGF-1 (LR3-IGF-1) is a potent IGF-1 analogue. We sought to determine whether intranasal (IN) LR3 treatment would delay cognitive decline and pathology in 5XFAD mice.
Aims: Central insulin has been shown to regulate eating behavior and cognitive processes in a sex-specific manner. Besides memory, the hippocampus is pivotal in the control of appetite. However, how insulin interacts with the hippocampal food cue response and the role of sex hormones in this context remain unclear.
