Protective effects of vasoactive intestinal peptide against delayed glutamate neurotoxicity in cultured retina

Shoge, Keisuke; Mishima, Hiromu K.; Saitoh, Tomoya; Ishihara, Kumatoshi; Tsutsumi, Yutaka; Shiomi, Hirohito; Sasa, Masashi

doi:10.1016/s0006-8993(98)00789-6

Cited by 33 publications

(21 citation statements)

References 37 publications

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“…The first report on the retinoprotective effects of PACAP was a study showing that PACAP protected cultured retinal neurons against glutamate toxicity 55 . This study was the logical continuation of a previous study of the same authors demonstrating similar protective effects of VIP, a peptide structurally related to PACAP 56 . Elevated glutamate concentrations lead to excitotoxic cell death in the nervous system, including apoptotic cell death in the retina 35,36 …”

Section: The In Vitro Retinoprotective Effects Of Pacapmentioning

confidence: 60%

Pituitary adenylate cyclase activating polypeptide in the retina: focus on the retinoprotective effects

Atlasz

Szabadfi

Kiss

et al. 2010

Annals of the New York Academy of Sciences

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Pituitary adenylate cyclase activating polypeptide (PACAP) is a neurotrophic and neuroprotective peptide that has been shown to exert protective effects against different neuronal injuries, such as traumatic brain and spinal cord injury, models of neurodegenerative diseases, and cerebral ischemia. PACAP and its receptors are present in the retina. In this study, we summarize the current knowledge on retinal PACAP with focus on the retinoprotective effects. Results of histological, immunohistochemical, and molecular biological analysis are reviewed. In vitro, PACAP shows protection against glutamate, thapsigargin, anisomycin, and anoxia. In vivo, the protective effects of intravitreal PACAP treatment have been shown in the following models of retinal degeneration in rats: excitotoxic injury induced by glutamate and kainate, ischemic injury, degeneration caused by UV-A light, optic nerve transection, and streptozotocin-induced diabetic retinopathy. Studying the molecular mechanism has revealed that PACAP acts by activating antiapoptotic and inhibiting proapoptotic signaling pathways in the retina in vivo. These studies strongly suggest that PACAP is an excellent candidate retinoprotective agent that could be a potential therapeutic substance in various retinal diseases.

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Section: The In Vitro Retinoprotective Effects Of Pacapmentioning

confidence: 60%

Pituitary adenylate cyclase activating polypeptide in the retina: focus on the retinoprotective effects

Atlasz

Szabadfi

Kiss

et al. 2010

Annals of the New York Academy of Sciences

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“…In addition, effects via the common VIP/PACAP receptors (VPAC1 and VPAC2) cannot be excluded, since these receptors are also present in the retina . Although the cAMP increasing effects of VIP is much less pronounced in various tissues, including the retina (Olianas et al, 1997;Shoge et al, 1999), protective effects of VIP in retinal ischemia/reperfusion injury and in vitro glutamate-toxicity have been demonstrated (Tuncel et al, 1996;Shoge et al, 1998).…”

Section: Discussionmentioning

confidence: 99%

Degree of damage compensation by various pacap treatments in monosodium glutamate-induced retinal degeneration

et al. 2005

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Pituitary adenylate cyclase activating polypeptide (PACAP) has been shown to be neuroprotective in retinal ischemia and monosodium L-glutamate (MSG)-induced retinal degeneration. Here we describe how different MSG treatments (1x and 3x application) cause retinal damage and finally lead to the destruction of the entire inner retina and how PACAP attenuates this effect. Newborn rats from both sexes were injected subcutaneously with 2 mg/g bodyweight MSG on postnatal days 1, 5 and 9. The left eye was left intact while we injected 5 microl PACAP38 solution (100 pmol) into the vitreous of the right eye with a Hamilton syringe at the time of (i) the first, (ii) the first two or (iii) all three MSG injections. Histological analysis has shown that the above described MSG treatment caused the entire inner plexiform layer (IPL) to degenerate, and the inner nuclear (INL) and ganglion cell layers (GCL) seemed fused. One time PACAP38 treatment at the first MSG application did not change the degenerative capacity of MSG. However, if animals received PACAP38 into the vitreous of the eye at the first 2 or all 3 times, a substantial protective effect could be observed. The IPL remained well discernible, the INL retained 2-3 cell rows and the number of cells in the GCL was substantially higher than in the MSG-treated retinas, and was not significantly different from that observed in the control tissue. We conclude that (i) 2 or 3 times PACAP treatment attenuates retinal degeneration; (ii) one PACAP treatment does not provide protection against repeated excitotoxic insults, and (iii) repeated application of PACAP under these experimental conditions may lead to a primed state in which further neurotoxic insults are ineffective.

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“…For studies involving antagonism of PACAP receptors, rats were bilaterally pretreated with saline, PACAP(6 -38) (500 pmol/0.25 l per side, Anaspec) or VIP(6 -28) (500 pmol/0.25 l per side, Bachem). PACAP(6 -38) is a widely used PAC1R antagonist; however, it also has antagonistic properties at the VPAC2R (19,27,40,52), and VIP(6 -28) is reported to be a potent nonselective VPAC receptor antagonist (16,38,54) shown to be effective in the hypothalamus (28). Five minutes later, rats received a second bilateral injection of either saline or 50 pmol PACAP followed by subsequent physiological and behavioral measurements.…”

Section: Methodsmentioning

confidence: 99%

Intrahypothalamic pituitary adenylate cyclase-activating polypeptide regulates energy balance via site-specific actions on feeding and metabolism

Resch

Maunze

Gerhardt

et al. 2013

American Journal of Physiology-Endocrinology and Metabolism

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Resch JM, Maunze B, Gerhardt AK, Magnuson SK, Phillips KA, Choi S. Intrahypothalamic pituitary adenylate cyclase-activating polypeptide regulates energy balance via site-specific actions on feeding and metabolism. Am J Physiol Endocrinol Metab 305: E1452-E1463, 2013. First published October 22, 2013; doi:10.1152/ajpendo.00293.2013.-Numerous studies have demonstrated that both the hypothalamic paraventricular nuclei (PVN) and ventromedial nuclei (VMN) regulate energy homeostasis through behavioral and metabolic mechanisms. Receptors for pituitary adenylate cyclase-activating polypeptide (PACAP) are abundantly expressed in these nuclei, suggesting PACAP may be critical for the regulation of feeding behavior and body weight. To characterize the unique behavioral and physiological responses attributed to select hypothalamic cell groups, PACAP was site-specifically injected into the PVN or VMN. Overall food intake was significantly reduced by PACAP at both sites; however, meal pattern analysis revealed that only injections into the PVN produced significant reductions in meal size, duration, and total time spent eating. PACAP-mediated hypophagia in both the PVN and VMN was abolished by PAC1R antagonism, whereas pretreatment with a VPACR antagonist had no effect. PACAP injections into the VMN produced unique changes in metabolic parameters, including significant increases in core body temperature and spontaneous locomotor activity that was PAC1R dependent whereas, PVN injections of PACAP had no effect. Finally, PACAP-containing afferents were identified using the neuronal tracer cholera toxin subunit B (CTB) injected unilaterally into the PVN or VMN. CTB signal from PVN injections was colocalized with PACAP mRNA in the medial anterior bed nucleus of the stria terminalis, VMN, and lateral parabrachial nucleus (LPB), whereas CTB signal from VMN injections was highly colocalized with PACAP mRNA in the medial amygdala and LPB. These brain regions are known to influence energy homeostasis perhaps, in part, through PACAP projections to the PVN and VMN.feeding; activity; temperature; hypothalamus; rat PITUITARY ADENYLATE CYCLASE-ACTIVATING polypeptide (PACAP) is a key regulator of several hypothalamic systems, including stress (1), osmoregulation (17), thermoregulation (21), and body weight (27). PACAP was first discovered to influence energy homeostasis through inhibition of feeding in mice following a single intracerebroventricular (icv) injection of the peptide (39). These results combined with reports of dietspecific alterations of PACAP mRNA expression in the hypothalamic ventromedial nuclei (VMN) suggest that PACAP is responsive to nutritional status and directly tied to metabolic systems linked to energy expenditure (27,40). In addition to reducing food intake, icv administration of PACAP modulates autonomic nerve activity (55) as well as hepatic glucose production (60). As a ligand, PACAP binds to three different G protein-coupled receptors, the PAC1 receptor (PAC1R), and the receptors originally discovered as targets...

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Protective effects of vasoactive intestinal peptide against delayed glutamate neurotoxicity in cultured retina

Cited by 33 publications

References 37 publications

Pituitary adenylate cyclase activating polypeptide in the retina: focus on the retinoprotective effects

Pituitary adenylate cyclase activating polypeptide in the retina: focus on the retinoprotective effects

Degree of damage compensation by various pacap treatments in monosodium glutamate-induced retinal degeneration

Intrahypothalamic pituitary adenylate cyclase-activating polypeptide regulates energy balance via site-specific actions on feeding and metabolism

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