Region-specific changes in the immunoreactivity of vasoactive intestinal peptide and pituitary adenylate cyclase-activating polypeptide receptors (VPAC2, and PAC1 receptor) in the aged rat brains

Lee, Jae Chul; Cho, Yu Jin; Kim, Jandi; Kim, Nahee; Kang, Bong Gu; Ik, Choong; Joo, Kyeung Min

doi:10.1016/j.brainres.2010.06.048

Cited by 21 publications

(18 citation statements)

References 37 publications

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“…Normal vascular responses are most likely achieved through receptor adaptation, as demonstrated already in young PACAP-KO mice [7]. It is unclear why carotid arteries of aging PACAP-KO mice improve PACAP1-38-induced relaxation, but we propose that increased receptor binding serves as a compensatory mechanism, especially if there is an increase in levels of PAC1R, as previously observed by Lee et al [26]. In addition, age-related vascular impairments and dysfunction [32] could also influence the magnitude of the vasomotor response to PACAP and VIP.…”

Section: Discussionsupporting

confidence: 54%

“…Tripathy et al [16] reported that the cerebrovascular level of PACAP is higher in young rats and lower in old rats. An interesting observation has been made regarding PACAP and VIP receptors in the brain of old rats showing increased PAC1R, decreased VPAC1R, and unchanged VPAC2R levels [26,27]. Several research groups have already attempted to identify possible compensatory mechanisms in PACAP deficiency.…”

Section: Discussionmentioning

confidence: 99%

“…During prenatal development and shortly after birth, there is a rapid increase in the mRNA and protein levels of PACAP and its receptors [1,26]. In contrast, these levels decrease with aging.…”

Section: Discussionmentioning

confidence: 99%

“…An age-related decrease in PACAP mRNA and protein levels [16,31] can alter PACAP-induced relaxation. Accordingly, in the old rat brain, Lee et al [26] reported increased PAC1R and unchanged VPAC2R levels with aging, which implies the adaptation of the PACAP system for either compensation (in the form of receptor overexpression) or switch to “alternative” PACAP-mediated responses (most likely VIP). The responses of arteries of aging PACAP-KO mice correspond with those of aging WT mice, suggesting that the signal transduction pathway is able to adapt as age progresses.…”

Section: Discussionmentioning

confidence: 99%

“…PACAP and VIP are highly conserved through evolution [1], indicating the importance of PACAP in a large array of physiological and pathophysiological processes [1,26]. During prenatal development and shortly after birth, there is a rapid increase in the mRNA and protein levels of PACAP and its receptors [1,26].…”

Section: Discussionmentioning

confidence: 99%

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Aging-Induced Modulation of Pituitary Adenylate Cyclase-Activating Peptide- and Vasoactive Intestinal Peptide-Induced Vasomotor Responses in the Arteries of Mice

Ivić¹,

Solymár

Fülöp³

et al. 2017

J Vasc Res

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Pituitary adenylate cyclase-activating peptide (PACAP; 1-38 and 1-27) and vasoactive intestinal peptide (VIP) are related neuropeptides of the secretin/glucagon family. Overlapping signaling through G-protein-coupled receptors mediates their vasomotor activity. We previously showed that PACAP deficiency (PACAP-KO) shifts the mechanisms of vascular response and maintains arterial relaxation through the VIP backup mechanism and (mainly) its VPAC1R, but their age-dependent modulation is still unknown. We hypothesized that backup mechanisms exist, which maintain the vasomotor activity of these peptides also in older age. Thus, we investigated the effects of exogenous VIP and PACAP peptides in isolated carotid arteries of 2- and 15-month-old wild-type (WT) and PACAP-KO mice. All peptides induced relaxation in the arteries of young WT mice, whereas in young PACAP-KO mice PACAP1-27 and VIP, but not PACAP1-38, induced relaxation. Unlike VIP, PACAP-induced vasomotor responses were reduced in aging WT mice. However, in the arteries of aging PACAP-KO mice, PACAP1-27- and VIP-induced responses were reduced, but PACAP1-38 showed a greater vasomotor response compared to that of young PACAP-KO animals. There were no significant differences between the vasomotor responses of aging WT and PACAP-KO mice. Our data suggest that, in the absence of PACAP both in young and old ages, the vascular response is mediated through backup mechanisms, most likely VIP, maintaining proper vascular relaxation in aging-induced PACAP insufficiency.

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Section: Discussionsupporting

confidence: 54%

Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

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Aging-Induced Modulation of Pituitary Adenylate Cyclase-Activating Peptide- and Vasoactive Intestinal Peptide-Induced Vasomotor Responses in the Arteries of Mice

Ivić¹,

Solymár

Fülöp³

et al. 2017

J Vasc Res

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Age-related changes in the distribution of transient receptor potential vanilloid 4 channel (TRPV4) in the central nervous system of rats

Lee

Choe

2014

J Mol Hist

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Transient receptor potential vanilloid type 4 (TRPV4) channels are expressed in the central nervous system, but their role in regulating the aging process under physiological and pathological conditions is still largely unknown. To identify age-related changes in the TRPV4 channel that contribute to the central nervous system, we investigated the distribution of TRPV4 in the brain and spinal cord regions of adult and aged rats. The expression of TRPV4 in the brain and spinal cord of adult and aged Sprague-Dawley rats was compared using immunohistochemistry performed with antibodies recognizing TRPV4 on free floating sections and western blotting analysis. TRPV4 immunoreactivity was significantly increased in the cerebral cortex, hippocampal formation, thalamus, basal nuclei, cerebellum and spinal cord of aged rats compared with adult control rats. In the cerebral cortex, TRPV4 immunoreactivity was significantly increased in pyramidal cells of aged rats. In addition, TRPV4 immunoreactivity was increased in the spinal cord, hippocampal formation, thalamus, basal nuclei and cerebellum of aged rats. This first demonstration of age-related increases in TRPV4 expression in the brain and spinal cord may provide useful data for investigating the pathogenesis of age-related neurodegenerative diseases. The exact regulatory mechanism and its functional significance require further elucidation.

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PACAP deficiency as a model of aging

et al. 2018

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Dysregulation of neuropeptides may play an important role in aging-induced impairments. In the long list of neuropeptides, pituitary adenylate cyclaseactivating polypeptide (PACAP) represents a highly effective cytoprotective peptide that provides an endogenous control against a variety of tissue-damaging stimuli. PACAP has neuro-and general cytoprotective effects due to anti-apoptotic, anti-inflammatory, and antioxidant actions. As PACAP is also a part of the endogenous protective machinery, it can be hypothesized that the decreased protective effects in lack of endogenous PACAP would accelerate age-related degeneration and PACAP knockout mice would display age-related degenerative signs earlier. Recent results support this hypothesis showing that PACAP deficiency mimics aspects of age-related pathophysiological changes including increased neuronal vulnerability and systemic degeneration accompanied by increased apoptosis, oxida-tive stress, and inflammation. Decrease in PACAP expression has been shown in different species from invertebrates to humans. PACAP-deficient mice display numerous pathological alterations mimicking early aging, such as retinal changes, corneal keratinization and blurring, and systemic amyloidosis. In the present review, we summarize these findings and propose that PACAP deficiency could be a good model of premature aging.

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Region-specific changes in the immunoreactivity of vasoactive intestinal peptide and pituitary adenylate cyclase-activating polypeptide receptors (VPAC2, and PAC1 receptor) in the aged rat brains

Cited by 21 publications

References 37 publications

Aging-Induced Modulation of Pituitary Adenylate Cyclase-Activating Peptide- and Vasoactive Intestinal Peptide-Induced Vasomotor Responses in the Arteries of Mice

Aging-Induced Modulation of Pituitary Adenylate Cyclase-Activating Peptide- and Vasoactive Intestinal Peptide-Induced Vasomotor Responses in the Arteries of Mice

Age-related changes in the distribution of transient receptor potential vanilloid 4 channel (TRPV4) in the central nervous system of rats

PACAP deficiency as a model of aging

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