Intranasal Delivery of a Peptide with Antidepressant-Like Effect

Brown, Virginia; Liu, Fang

doi:10.1038/npp.2014.61

Cited by 29 publications

(23 citation statements)

References 51 publications

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“…3A ). To target Fas in vivo we utilized the IN route to deliver FBP directly to the brain using a pressurized olfactory device (POD) 35 . Intranasal inoculation of A 488 -labeled FBP resulted in brain localization of the fluorescence labeled peptide in normal as well as MCAO-induced rats at 12 h (Fig.…”

Section: Resultsmentioning

confidence: 99%

Intranasal delivery of a Fas-blocking peptide attenuates Fas-mediated apoptosis in brain ischemia

Ullah

Chung

et al. 2018

Sci Rep

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Ischemic stroke-induced neuronal cell death results in the permanent disabling of brain function. Apoptotic mechanisms are thought to play a prominent role in neuronal injury and ample evidence implicates Fas signaling in mediating cell death. In this study, we describe the neuroprotective effects of a Fas-blocking peptide (FBP) that by obstructing Fas signaling in cerebral ischemia inhibits apoptosis. Using an intranasal administration route in a rat model of focal cerebral ischemia, we demonstrate that nose-to-brain delivery of FBP after middle cerebral artery occlusion (MCAO) surgery results in the delivery and retention of FBP in Fas-expressing ischemic areas of the brain. A single intranasal administration of 2 mg/kg FBP resulted in significantly reduced neuronal cell death by inhibiting Fas-mediated apoptosis leading to decreased infarct volumes, reduced neurologic deficit scores and recovery from cerebral ischemia. Intranasally delivered FBP might be a promising strategy for the treatment of cerebral ischemic stroke.

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Section: Resultsmentioning

confidence: 99%

Intranasal delivery of a Fas-blocking peptide attenuates Fas-mediated apoptosis in brain ischemia

Ullah

Chung

et al. 2018

Sci Rep

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“…The results of the present study indicate that oxytocin may have the potential to reduce heavy drinking in moderate to severe alcohol use disorder. (2) Oxytocin’s anti-drinking effects in rats can be achieved by intranasal administration, using a device designed to allow noninvasive drug delivery across the blood-brain barrier [53]. (3) Intranasal administration reduced alcohol consumption and motivation for alcohol in dependent rats without causing nonspecific locomotor, grooming, motor coordination, and consumption of nonalcoholic sweet or caloric palatable solutions, suggesting that oxytocin’s effects on alcohol drinking are specific to the pharmacological effects of alcohol.…”

Section: Discussionmentioning

confidence: 99%

Oxytocin blocks enhanced motivation for alcohol in alcohol dependence and blocks alcohol effects on GABAergic transmission in the central amygdala

et al. 2019

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Oxytocin administration has been reported to decrease consumption, withdrawal, and drug-seeking associated with several drugs of abuse and thus represents a promising pharmacological approach to treat drug addiction. We used an established rat model of alcohol dependence to investigate oxytocin’s effects on dependence-induced alcohol drinking, enhanced motivation for alcohol, and altered GABAergic transmission in the central nucleus of the amygdala (CeA). Intraperitoneal oxytocin administration blocked escalated alcohol drinking and the enhanced motivation for alcohol in alcohol-dependent but not nondependent rats. Intranasal oxytocin delivery fully replicated these effects. Intraperitoneal administration had minor but significant effects of reducing locomotion and intake of non-alcoholic palatable solutions, whereas intranasal oxytocin administration did not. In dependent rats, intracerebroventricular administration of oxytocin or the oxytocin receptor agonist PF-06655075, which does not cross the blood-brain barrier (i.e., it would not diffuse to the periphery), but not systemic administration of PF-06655075 (i.e., it would not reach the brain), decreased alcohol drinking. Administration of a peripherally restricted oxytocin receptor antagonist did not reverse the effect of intranasal oxytocin on alcohol drinking. Ex vivo electrophysiological recordings from CeA neurons indicated that oxytocin decreases evoked GABA transmission in nondependent but not in dependent rats, whereas oxytocin decreased the amplitude of spontaneous GABAergic responses in both groups. Oxytocin blocked the facilitatory effects of acute alcohol on GABA release in the CeA of dependent but not nondependent rats. Together, these results provide converging evidence that oxytocin specifically and selectively blocks the enhanced motivation for alcohol drinking that develops in alcohol dependence likely via a central mechanism that may result from altered oxytocin effects on CeA GABA transmission in alcohol dependence. Neuroadaptations in endogenous oxytocin signaling may provide a mechanism to further our understanding of alcohol use disorder.

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“…Thus in our study, we chose intranasal administration of IFNβ treatment since it is clinically viable and noninvasive ( Brown and Liu, 2014 ). Also intranasal delivery of IFNβ has previously been shown to effectively bypass the blood–brain barrier and directly target the CNS in a rat model of multiple sclerosis ( Ross et al., 2004 ).…”

Section: Discussionmentioning

confidence: 99%

Intranasal Administration of Interferon Beta Attenuates Neuronal Apoptosis via the JAK1/STAT3/BCL-2 Pathway in a Rat Model of Neonatal Hypoxic-Ischemic Encephalopathy

et al. 2016

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Neonatal hypoxic-ischemic encephalopathy (HIE) is an injury that often leads to detrimental neurological deficits. Currently, there are no established therapies for HIE and it is critical to develop treatments that provide protection after HIE. The objective of this study was to investigate the ability of interferon beta (IFNβ) to provide neuroprotection and reduce apoptosis after HIE. Postnatal Day 10 rat pups were subjected to unilateral carotid artery ligation followed by 2.5 hr of exposure to hypoxia (8% O2). Intranasal administration of human recombinant IFNβ occurred 2 hr after HIE and infarct volume, body weight, neurobehavioral tests, histology, immunohistochemistry, brain water content, blood–brain barrier permeability, enzyme-linked immunosorbent assay, and Western blot were all used to evaluate various parameters. The results showed that both IFNβ and the Type 1 interferon receptor expression decreases after HIE. Intranasal administration of human recombinant IFNβ was able to be detected in the central nervous system and was able to reduce brain infarction volumes and improve neurological behavior tests 24 hr after HIE. Western blot analysis also revealed that human recombinant IFNβ treatment stimulated Stat3 and Bcl-2 expression leading to a decrease in cleaved caspase-3 expression after HIE. Positive Fluoro-Jade C staining also demonstrated that IFNβ treatment was able to decrease neuronal apoptosis. Furthermore, the beneficial effects of IFNβ treatment were reversed when a Stat3 inhibitor was applied. Also an intraperitoneal administration of human recombinant IFNβ into the systemic compartment was unable to confer the same protective effects as intranasal IFNβ treatment.

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Intranasal Delivery of a Peptide with Antidepressant-Like Effect

Cited by 29 publications

References 51 publications

Intranasal delivery of a Fas-blocking peptide attenuates Fas-mediated apoptosis in brain ischemia

Intranasal delivery of a Fas-blocking peptide attenuates Fas-mediated apoptosis in brain ischemia

Oxytocin blocks enhanced motivation for alcohol in alcohol dependence and blocks alcohol effects on GABAergic transmission in the central amygdala

Intranasal Administration of Interferon Beta Attenuates Neuronal Apoptosis via the JAK1/STAT3/BCL-2 Pathway in a Rat Model of Neonatal Hypoxic-Ischemic Encephalopathy

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