Insulin/PI3K signaling protects dentate neurons from oxygen–glucose deprivation in organotypic slice cultures

Sun, Xingzhi; Yao, Heng‐Chen; Douglas, Robert M.; Gu, Xiang; Wang, Juan; Haddad, Gabriel G.

doi:10.1111/j.1471-4159.2009.06450.x

Cited by 48 publications

(47 citation statements)

References 56 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…However, in an in vitro model of ischemia used by Hamabe et al, coincubation of neurons with insulin during 2 h of oxygen-glucose deprivation (as a model of cerebral ischemia) significantly decreased the hypoxia-induced neuronal necrosis [264]. In another study, Sun et al reported that insulin protection against neuronal injury induced by oxygen-glucose deprivation may vary in different subregions of the hippocampus, as the dentate gyrus was reported to be more sensitive to insulin neuroprotection and less vulnerable to ischemia, but CA-1 and CA-3 were reported to be less sensitive to insulin and more vulnerable to ischemia [291].…”

Section: Protective Effects Against Ischemiamentioning

confidence: 99%

Insulin in the Brain: Sources, Localization and Functions

et al. 2012

View full text Add to dashboard Cite

Historically, insulin is best known for its role in peripheral glucose homeostasis, and insulin signaling in the brain has received less attention. Insulin-independent brain glucose uptake has been the main reason for considering the brain as an insulin-insensitive organ. However, recent findings showing a high concentration of insulin in brain extracts, and expression of insulin receptors (IRs) in central nervous system tissues have gathered considerable attention over the sources, localization, and functions of insulin in the brain. This review summarizes the current status of knowledge of the peripheral and central sources of insulin in the brain, site-specific expression of IRs, and also neurophysiological functions of insulin including the regulation of food intake, weight control, reproduction, and cognition and memory formation. This review also considers the neuromodulatory and neurotrophic effects of insulin, resulting in proliferation, differentiation, and neurite outgrowth, introducing insulin as an attractive tool for neuroprotection against apoptosis, oxidative stress, beta amyloid toxicity, and brain ischemia.

show abstract

Section: Protective Effects Against Ischemiamentioning

confidence: 99%

Insulin in the Brain: Sources, Localization and Functions

et al. 2012

View full text Add to dashboard Cite

show abstract

“…Currently, direct evidence supporting this notion is limited to in vitro studies. For instance, it has been shown that insulin could protect neurons against a variety of insults, including glucose-oxygen deprivation (Sun et al, 2010), excitotoxicity (Kim and Han, 2005), and oxidative stress (Ribeiro et al, 2014). The neuroprotective action of insulin in vivo, however, remains unexplored.…”

Section: Introductionmentioning

confidence: 99%

Intranasal insulin protects against substantia nigra dopaminergic neuronal loss and alleviates motor deficits induced by 6-OHDA in rats

et al. 2016

View full text Add to dashboard Cite

Protection of substantia nigra (SN) dompaminergic (DA) neurons by neurotrophic factors (NTF) is one of the promising strategies in Parkinson’s disease (PD) therapy. A major clinical challenge for NTF-based therapy is that NTFs need to be delivered into the brain via invasive means, which often shows limited delivery efficiency. The nose to brain pathway is a non-invasive brain drug delivery approach developed in recent years. Of particular interest is the finding that intranasal insulin improves cognitive functions in Alzheimer’s patients. In vitro, insulin has been shown to protect neurons against various insults. Therefore, the current study was designed to test whether intranasal insulin could afford neuroprotection in the 6-hydroxylase dopamine (6-OHDA)-based rat PD model. 6-OHDA was injected into the right side of striatum to induce a progressive DA neuronal lesion in the ipsilateral SN pars compact (SNc). Recombinant human insulin was applied intranasally to rats starting from 24 h post lesion, once per day, for 2 weeks. A battery of motor behavioral tests was conducted on day 8 and 15. The number of DA neurons in the SNc was estimated by stereological counting. Our results showed that 6-OHDA injection led to significant motor deficits and a 53% of DA neuron loss in the ipsilateral side of injection. Treatment with insulin significantly ameliorated 6-OHDA-induced motor impairments, as shown in improved locomotor activity, tapered/ledged beam walking performance, Vibrissa-elicited forelimb-placing, initial steps, as well as methamphetamine-induced rotational behavior. Consistent with behavioral improvements, insulin treatment provided a potent protection of DA neurons in the SNc against 6-OHDA neurotoxicity, as shown by a 74.8 % of increase in tyrosine hydrolase (TH) positive neurons compared to the vehicle group. Intranasal insulin treatment did not affect body weight and blood glucose levels. In conclusion, our study showed that intranasal insulin provided strong neuroprotection in the 6-OHDA rat PD model, suggesting that insulin signaling may be a novel therapeutic target in a broad neurodegenerative disorders.

show abstract

“…This function of PTEN directly antagonizes PI3K to eventually down-regulate AKT (21,22). Several lines of evidence indicated that the AKT signaling pathway responds to oxidative stress (23) and exerts a neuroprotective function (24,25). Moreover, a large number of studies in vitro have illustrated that pharmacological compounds that protect cells against oxidative stress exert their neuroprotective effects through activation of the AKT pathway (26)(27)(28)(29)(30).…”

mentioning

confidence: 99%

DJ-1 protects the nigrostriatal axis from the neurotoxin MPTP by modulation of the AKT pathway

Aleyasin

Rousseaux

Marcogliese

et al. 2010

Proc. Natl. Acad. Sci. U.S.A.

155

118

View full text Add to dashboard Cite

Loss-of-function DJ-1 (PARK7) mutations have been linked with a familial form of early onset Parkinson disease. Numerous studies have supported the role of DJ-1 in neuronal survival and function. Our initial studies using DJ-1-deficient neurons indicated that DJ-1 specifically protects the neurons against the damage induced by oxidative injury in multiple neuronal types and degenerative experimental paradigms, both in vitro and in vivo. However, the manner by which oxidative stress-induced death is ameliorated by DJ-1 is not completely clear. We now present data that show the involvement of DJ-1 in modulation of AKT, a major neuronal prosurvival pathway induced upon oxidative stress. We provide evidence that DJ-1 promotes AKT phosphorylation in response to oxidative stress induced by H 2 O 2 in vitro and in vivo following 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) treatment. Moreover, we show that DJ-1 is necessary for normal AKT-mediated protective effects, which can be bypassed by expression of a constitutively active form of AKT. Taken together, these data suggest that DJ-1 is crucial for full activation of AKT upon oxidative injury, which serves as one explanation for the protective effects of DJ-1.neurodegeneration | Parkinson disease | reactive oxygen species

show abstract

Insulin/PI3K signaling protects dentate neurons from oxygen–glucose deprivation in organotypic slice cultures

Cited by 48 publications

References 56 publications

Insulin in the Brain: Sources, Localization and Functions

Insulin in the Brain: Sources, Localization and Functions

Intranasal insulin protects against substantia nigra dopaminergic neuronal loss and alleviates motor deficits induced by 6-OHDA in rats

DJ-1 protects the nigrostriatal axis from the neurotoxin MPTP by modulation of the AKT pathway

Contact Info

Product

Resources

About