Pituitary Adenylate Cyclase-Activating Polypeptide in the Ventromedial Hypothalamus Is Responsible for Food Intake Behavior by Modulating the Expression of Agouti-Related Peptide in Mice

Nguyen, Thanh Trung; Kambe, Yuki; Kurihara, Takashi; Nakamachi, Tomoya; Shintani, Norihito; Hashimoto, Hitoshi; Miyata, Atsuro

doi:10.1007/s12035-019-01864-7

Cited by 21 publications

(26 citation statements)

References 50 publications

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“…Here I increased the depth of the injection to 5.72mm from the brain surface and decreased the concentration of the virus by 10-fold. The reduction in concentration was supported by a recent, independent study, which showed successful expression of PACAP protein using an adeno-associated virus in the VMN, using 2 x 10 13 viral genome/ml (Nguyen et al, 2020), which is comparable to the dose we delivered (2.14 x 10 13 ). In conclusion, the combination of using revised coordinates and the reduced concentration of virus outlined in this ICV protocol successfully induced expression of eGFP specifically in the VMN of the hypothalamus (Figure 2.4).…”

Section: Discussionsupporting

confidence: 67%

Experimental approach to overexpress pituitary adenylate cyclase activating polypeptide (PACAP) specifically in the hypothalamus

Rahim¹

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Obesity is adetrimental health condition that occurs when energy intake, exceeds energy expenditure. Pituitary adenylatecyclase-activating polypeptide (PACAP) regulates energy expenditure, including adaptive thermogenesis, through the hypothalamic-sympatheticnervous system-brown adipose tissue axis. We hypothesize that PACAP expression in the ventromedial nucleus (VMN) is required for adaptive thermogenesis. To assess this, our goal is to develop an animal model that expresses PACAP specifically in the VMN of the hypothalamus. As a first step to achieving this goal, we established a protocol to deliver an adeno-associatedvirus (AAV) expressing the visible protein eGFP under the control of a VMN-specific promoter, steroidogenic factor 1 (SF1) using stereotaxic surgery. A second step was to develop a protocol to detect PACAP mRNA in the brain using in situ hybridization. Our results showed that the stereotaxic protocol was successful and provides significant progress towards achieving PACAP-specific expression in the VMN.

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Section: Discussionsupporting

confidence: 67%

Experimental approach to overexpress pituitary adenylate cyclase activating polypeptide (PACAP) specifically in the hypothalamus

Rahim¹

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“…Complete PACAP deficiency in PACAP homozygous knockout mice has been shown to have severe consequences in numerous physiological and pathological processes. Among others, mice with a complete lack of PACAP have high mortality, altered axonal arborization in the dentate gyrus [63], disturbed energy balance [64], and reduced food intake [65]. PACAP deficiency leads to increased vulnerability towards different stressors.…”

Section: Discussionmentioning

confidence: 99%

Presence of Systemic Amyloidosis in Mice with Partial Deficiency in Pituitary Adenylate Cyclase-Activating Polypeptide (PACAP) in Aging

et al. 2021

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Pituitary adenylate cyclase-activating polypeptide (PACAP), a neuropeptide with widespread expression and general cytoprotective effects, is also involved in aging. Previously, we observed accelerated systemic senile amyloidosis in PACAP knockout (KO) mice. As mice partially lacking PACAP (heterozygous-HZ) show variable symptoms, here we investigated whether HZ mice have accelerated aging, completed with observations in PAC1 receptor KO mice. As we have limited data on qualitative or quantitative changes in the blood of PACAP-deficient mice, we investigated whether these changes could be in the background of the amyloidosis. Routine histological staining was used to examine amyloid deposits, rated on a severity scale 0–3. Blood was collected from PACAP wild type/HZ mice for complete blood analysis. In contrast to receptor KO mice showing no amyloidosis, histopathological analysis revealed severe deposits in PACAP HZ mice, with kidney, spleen, skin, and intestines being most affected. Increased cholesterol, lipoprotein levels, and differences in several blood count parameters were found in HZ mice. In summary, amyloidosis also develops in partial absence of PACAP, in contrast to the lack of its PAC1 receptor. In addition to the earlier identified inflammatory and degenerative disturbances, the alteration in lipid metabolism and bone marrow activity can also be additional factors leading to systemic degenerative processes.

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“…Pituitary adenylate cyclase-activating polypeptide (PACAP) was initially isolated from the ovine hypothalamus as an activator of adenylyl cyclase in pituitary cells [10]. PACAP is made up of 38 amino-acid residues (PACAP38) and is C-terminally alpha-amidated; the sequence encompasses an internal cleavage-amidation site that generates a 27-residue alpha-amidated polypeptide fragment or PACAP27, which corresponds to the N-terminal 27 amino-acid portion of the PACAP38 [11].…”

Section: Pacap Its Receptors and Its Physiological Rolesmentioning

confidence: 99%

The PACAP/PAC1 Receptor System and Feeding

Kumar¹,

Saenz²,

Ahmad³

et al. 2021

Preprint

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Pituitary adenylyl cyclase activating polypeptide (PACAP) belongs to the vasoactive intestinal polypeptide (VIP)/secretin/glucagon superfamily. PACAP is present in two forms, PACAP-38 and PACAP-27, and binds to three guanine-regulatory (G) protein-coupled receptors (PAC1, VPAC1, and VPAC2). PACAP is expressed in the central and peripheral nervous systems with high PACAP levels found in the hypothalamus, a brain region involved in feeding and energy homeostasis. PAC1 receptors are high-affinity and PACAP-selective receptors, while VPAC1 and VPAC2 receptors show a comparable affinity to PACAP and VIP. PACAP and its receptors are expressed in the central and peripheral nervous systems, with moderate to high expression in the hypothalamus, amygdala, and other limbic structures. Consistent with their expression, PACAP is involved in several physiological responses and pathological states. A growing body of literature suggests that PACAP regulates food intake in laboratory animals. However, there is no comprehensive review of the literature on this topic. Thus, the purpose of this article is to review the literature regarding the role of PACAP and its receptors in food intake regulation and to synthesize how PACAP exerts its anorexic effects in different brain regions. To achieve this goal, we searched PubMed and reviewed 68 articles regarding the regulatory action of PACAP on food intake. Here, we present the literature regarding the effect of exogenous PACAP on feeding and the role of endogenous PACAP in this process. We also provide evidence regarding the effect of PACAP on the homeostatic and hedonic aspects of food intake, the neuroanatomical sites where PACAP exerts its regulatory action, which PACAP receptors may be involved, and the role of various signaling pathways and neurotransmitters in hypophagic effects of PACAP.

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Pituitary Adenylate Cyclase-Activating Polypeptide in the Ventromedial Hypothalamus Is Responsible for Food Intake Behavior by Modulating the Expression of Agouti-Related Peptide in Mice

Cited by 21 publications

References 50 publications

Experimental approach to overexpress pituitary adenylate cyclase activating polypeptide (PACAP) specifically in the hypothalamus

Experimental approach to overexpress pituitary adenylate cyclase activating polypeptide (PACAP) specifically in the hypothalamus

Presence of Systemic Amyloidosis in Mice with Partial Deficiency in Pituitary Adenylate Cyclase-Activating Polypeptide (PACAP) in Aging

The PACAP/PAC1 Receptor System and Feeding

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