Kinetics of arginine-vasopressin uptake at the blood-brain barrier

Zloković, Berislav V.; Hyman, Shigeyo; McComb, J. Gordon; Lipovac, M. N.; Tang, Gong‐Li; Davson, Hugh

doi:10.1016/0005-2736(90)90097-8

Cited by 100 publications

(50 citation statements)

References 41 publications

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“…However, nutrients such as glucose, amino acids, and vitamins cross the BBB using specific transporters (48). Peptides in general poorly cross the BBB (49,50), but can be transported into the brain if specific transporters and/or receptors with a transport function are expressed in brain endothelium either under physiological (51,52) or pathological conditions, as in the case of RAGE and Aβ transport (43). Recent studies have independently confirmed earlier observations that circulating Aβ is an important precursor for brain Aβ (7,10,33) by demonstrating that peripheral Aβ can accelerate cerebral β-amyloidosis in a mouse model (11) and that liver serves as an important source of brain Aβ (53).…”

Section: Discussionmentioning

confidence: 99%

A multimodal RAGE-specific inhibitor reduces amyloid β–mediated brain disorder in a mouse model of Alzheimer disease

Deane¹,

Singh²,

Sagare³

et al. 2012

J. Clin. Invest.

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517

446

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In Alzheimer disease (AD), amyloid β peptide (Aβ) accumulates in plaques in the brain. Receptor for advanced glycation end products (RAGE) mediates Aβ-induced perturbations in cerebral vessels, neurons, and microglia in AD. Here, we identified a high-affinity RAGE-specific inhibitor (FPS-ZM1) that blocked Aβ binding to the V domain of RAGE and inhibited Aβ40-and Aβ42-induced cellular stress in RAGE-expressing cells in vitro and in the mouse brain in vivo. FPS-ZM1 was nontoxic to mice and readily crossed the blood-brain barrier (BBB). In aged APP sw/0 mice overexpressing human Aβ-precursor protein, a transgenic mouse model of AD with established Aβ pathology, FPS-ZM1 inhibited RAGE-mediated influx of circulating Aβ40 and Aβ42 into the brain. In brain, FPS-ZM1 bound exclusively to RAGE, which inhibited β-secretase activity and Aβ production and suppressed microglia activation and the neuroinflammatory response. Blockade of RAGE actions at the BBB and in the brain reduced Aβ40 and Aβ42 levels in brain markedly and normalized cognitive performance and cerebral blood flow responses in aged APP sw/0 mice. Our data suggest that FPS-ZM1 is a potent multimodal RAGE blocker that effectively controls progression of Aβ-mediated brain disorder and that it may have the potential to be a disease-modifying agent for AD.

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Section: Discussionmentioning

confidence: 99%

A multimodal RAGE-specific inhibitor reduces amyloid β–mediated brain disorder in a mouse model of Alzheimer disease

Deane¹,

Singh²,

Sagare³

et al. 2012

J. Clin. Invest.

Self Cite

517

446

View full text Add to dashboard Cite

show abstract

“…Early studies seemed to indicate that oxytocin and vasopressin, or at least physiologically significant amounts of these peptides, are excluded access to most regions of the CNS by the blood-brain barrier (BBB) (Ermisch et al, 1988;Meisenberg and Simmons, 1983b). However, more recently, a bidirectional saturable active transport mechanism across the BBB has been demonstrated for vasopressin (Banks et al, 1987;Zlokovic et al, 1990). The behavioral effects of peripherally circulating peptides may be indirect such as via the alteration of the BBB permeability to other substances.…”

Section: Discussionmentioning

confidence: 99%

Oxytocin Infusion Reduces Repetitive Behaviors in Adults with Autistic and Asperger's Disorders

Hollander

Novotny

Hanratty

et al. 2003

Neuropsychopharmacol

621

403

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Autism is a neurodevelopmental disorder characterized by dysfunction in three core behavioral domains: repetitive behaviors, social deficits, and language abnormalities. There is evidence that abnormalities exist in peptide systems, particularly the oxytocin system, in autism spectrum patients. Furthermore, oxytocin and the closely related peptide vasopressin are known to play a role in social and repetitive behaviors. This study examined the impact of oxytocin on repetitive behaviors in 15 adults with autism or Asperger's disorder via randomized double-blind oxytocin and placebo challenges. The primary outcome measure was an instrument rating six repetitive behaviors: need to know, repeating, ordering, need to tell/ask, self-injury, and touching. Patients with autism spectrum disorders showed a significant reduction in repetitive behaviors following oxytocin infusion in comparison to placebo infusion. Repetitive behavior in autism spectrum disorders may be related to abnormalities in the oxytocin system, and may be partially ameliorated by synthetic oxytocin infusion.

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“…Future studies are needed to determine if AVT treatment impacts behavior independently via effects on the brain or if the observed effects work primarily through its activation of the HPA axis and stimulation of corticosterone release. There is some indication, in mammals, that a small but measurable portion of peripherally administered radiolabelled-AVP can cross the blood-brain barrier (Zlokovic et al, 1990). While there have been several studies on the structure and permeability of the blood-brain barrier in the green anole (Kenny and Shivers, 1974;Shivers, 1979;Shivers and Harris, 1984), the specific permeability to AVT has not been examined.…”

Section: Research Articlementioning

confidence: 99%

Arginine vasotocin, steroid hormones, and social behavior in the green anole lizard, Anolis carolinensis

Dunham

Wilczynski

2014

Journal of Experimental Biology

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Arginine vasotocin (AVT) is a potent regulator of social behavior in many species, but little is known about its role in reptilian behavior. Here we examine the effect of exogenous AVT on aggressive responding and courtship behavior in the green anole lizard (Anolis carolinensis). Aggressive behavior was stimulated in two ways: (1) mirror presentation (no relative status formed) and (2) size-matched pairs (where a social status is achieved). To elicit courtship behavior, a novel female was introduced into the home cage of a male. Regardless of the behavior condition, male anoles were injected i.p. with either reptile Ringer solution (vehicle) or AVT prior to testing. Animals treated with AVT performed fewer aggressive display bouts during mirror presentation but AVT treatment did not affect the overall number of aggressive display bouts within size-matched pairs. Male courtship behavior was not affected by AVT; however, untreated females displayed more frequently when paired with an AVT-treated male than a vehicle-injected control, suggesting that AVT-treated males were more attractive to females. Regardless of behavior condition, AVT injections led to increases in circulating corticosterone. Overall, we found that AVT tended to reduce aggressive behavior as has been reported for other territorial species. AVT did not perceptibly alter male courtship but did increase the display behavior of untreated females paired with treated males. Our study supports a role for AVT in the regulation of reptile social behavior.

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Kinetics of arginine-vasopressin uptake at the blood-brain barrier

Cited by 100 publications

References 41 publications

A multimodal RAGE-specific inhibitor reduces amyloid β–mediated brain disorder in a mouse model of Alzheimer disease

A multimodal RAGE-specific inhibitor reduces amyloid β–mediated brain disorder in a mouse model of Alzheimer disease

Oxytocin Infusion Reduces Repetitive Behaviors in Adults with Autistic and Asperger's Disorders

Arginine vasotocin, steroid hormones, and social behavior in the green anole lizard, Anolis carolinensis

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