McDougle M, Quinn D, Diepenbroek C, Singh A, de la Serre C, de Lartigue G (2021) Intact vagal gut-brain signalling prevents hyperphagia and excessive weight gain in response to high-fat high-sugar diet. Acta Physiol (Oxf) 231(3):e13530. doi: 10.1111/apha.13530

Objective: To assess the function of the vagus nerve lack specificity.

Summary: Intact sensory vagal neurons prevent hyperphagia and exacerbation of weight gain in response to a HFHS diet by promoting lipid-mediated satiation.

Usage: Rat nodose ganglia were injected bilaterally with either CCK-SAP or unconjugated saporin as a control.

Related Products: CCK-SAP (Cat. #IT-31)

Lee TH, Yau SY (2021) From obesity to hippocampal neurodegeneration: Pathogenesis and non-pharmacological interventions. Int J Mol Sci 22(1):201. doi: 10.3390/ijms22010201

Summary: This review provides insights into how chronic metabolic disorders, like obesity, could impair brain health and cognitive functions in later life. The authors reference the use of CCK-SAP into the nodose ganglia to impair spatial memory and contextual episodic memory.

See: Suarez AN et al. Gut vagal sensory signaling regulates hippocampus function through multi-order pathways. Nat Commun 9(1):2181, 2018.

Related Products: CCK-SAP (Cat. #IT-31)

Krieger JP (2020) Intestinal glucagon-like peptide-1 effects on food intake: Physiological relevance and emerging mechanisms. Peptides 131:170342. doi: 10.1016/j.peptides.2020.170342 PMID: 32522585

Objective: Review of findings of GLP-1 involvement in obesity.

Summary: The most selective method of gastrointestinal vagal deafferentation to date used CCK-SAP injected into the nodose ganglia which blunts the anorexigenic effect of IP GLP-1 administration.

Related Products: CCK-SAP (Cat. #IT-31)

See Also:

• Diepenbroek C et al. Validation and characterization of a novel method for selective vagal deafferentation of the gut. Am J Physiol Gastrointest Liver Physiol 313:G342-G352, 2017.

Tominaga M, Kusube F, Honda K, Komiya E, Takahashi N, Naito H, Suga Y, Takamori K (2019) OP11: Role of spinal cholecystokinin receptor 2 in alloknesis models. Itch 4:1-62. doi: 10.1097/itx.0000000000000030

Objective: To determine the detailed molecular and cellular mechanisms that induce alloknesis via the spinal CCK2 receptor.

Summary: Ablation of spinal CCK receptor-expressing cells by i.t. injection of CCK-SAP attenuated CCK8S-induced alloknesis in comparison with Blank-SAP control mice.

Usage: Intrathecal injection

Related Products: CCK-SAP (Cat. #IT-31), Blank-SAP (Cat. #IT-21)

Suarez AN, Liu CM, Cortella AM, Noble EN, Kanoski SE (2019) Medial septum cholinergic signaling regulates gastrointestinal-derived vagus sensory nerve communication to the hippocampus. Neuroscience 2019 Abstracts 601.19. Society for Neuroscience, Chicago, IL.

Summary: The vagus nerve delivers bi-directional communication between feeding-relevant gastrointestinal (GI) signals and the brain. Vagal sensory-mediated GI satiation signals, including gastric distension and intra-gastric nutrient infusion, activate neurons in the hippocampus (HPC). Recent work from our lab revealed that selective GI-derived vagal sensory signaling is required for HPC-dependent episodic and visuospatial memory, effects accompanied by reduced dorsal HPC (dHPC) expression of neurotrophic and neurogenic markers. To investigate the neural pathways mediating gut regulation of hippocampal-dependent memory, here we investigate the hypothesis that GI-derived signals communicate to dHPC neurons via cholinergic input from the medial septum, a memory-promoting pathway that is vulnerable to disruption in various degenerative dementia diseases. To explore this putative gut-to-brain pathway, we administered 192IgG-saporin, a neurotoxin that selectively kills cholinergic neurons via apoptosis, in the medial septum to determine whether septal cholinergic neurons regulate vagally-mediated neuronal activation in dHPC. Results revealed that elimination of cholinergic neurons in the MS reduced peripherally-administered cholecystokinin (CCK)-induced c-Fos expression in the dHPC, suggesting that cholinergic inputs from the MS transmit GI-derived signaling to the dHPC. Consistent with this interpretation, dHPC protein expression of vesicular acetylcholine transporter (VAChT), which promotes memory function and acetylcholine release without disrupting other co- released molecules, was significantly reduced in rats with GI-specific vagal sensory ablation via nodose ganglion injections of CCK conjugated to saporin. Collectively these results suggest that GI-derived vagal sensory signaling infuences memory function via enhancement of MS cholinergic signaling to the dPHC.

Related Products: 192-IgG-SAP (Cat. #IT-01), CCK-SAP (Cat. #IT-31)

Suarez AN, Noble EE, Kanoski SE (2019) Regulation of memory function by feeding-relevant biological systems: Following the breadcrumbs to the hippocampus. Front Mol Neurosci 12:101. doi: 10.3389/fnmol.2019.00101 PMID: 31057368

Objective: To review the literature describing interconnections between the memory and feeding circuits of the body.

Summary: Gastrointestinal and memory systems within the body are heavily intertwined, something that has been evolutionarily selected for by having to remember food locations, social factors, etc. CCK-SAP (IT-31) has been used to study the connection of gastrointestinal-derived vagal-sensory neurons by selectively lesioning them. These CCK-SAP-treated rats were compared to un-lesioned animals and showed reduced brain-derived neurotrophic factor and memory impairment

Related Products: CCK-SAP (Cat. #IT-31)

See Also:

• Suarez AN et al. Gut vagal sensory signaling regulates hippocampus function through multi-order pathways. Nat Commun 9(1):2181, 2018.

Han W, Tellez LA, Perkins MH, Perez IO, Qu T, Ferreira J, Ferreira TL, Quinn D, Liu Z-W, Gao X-B, Kaelberer MM, Bohórquez DV, Shammah-Lagnado SJ, de Lartigue G, de Araujo IE (2018) A neural circuit for gut-induced reward. Cell 175:665-678. doi: 10.1016/j.cell.2018.08.049

Objective: To determine relevant gut-brain neuronal circuitry to motivational and emotional states.

Summary: There is a critical role for the vagal gut-to-brain axis in motivation and reward.

Usage: Injected 0.5 µl of CCK-SAP (250 ng/µl) into the R-NG of VGlut2-ires-Cre mice.

Related Products: CCK-SAP (Cat. #IT-31)

Suarez AN, Hsu TM, Liu CM, Noble EE, Cortella AM, Nakamoto EM, Hahn JD, de Lartigue G, Kanoski SE (2018) Gut vagal sensory signaling regulates hippocampus function through multi-order pathways. Nat Commun 9(1):2181. doi: 10.1038/s41467-018-04639-1

Objective: To determine the  endogenous relevance of GIderived vagal HPC communication.

Summary: Endogenous derived vagal sensory signaling promotes HPC-dependent memory function via a multi-order brainstem–septal pathway, thereby identifying a previously unknown role for the gut–brain axis in memory control.

Usage: A 1-µl volume of CCK-SAP (250 ng/µl) or control Saporin (250 ng/µl) was injected at two sites: 0.5 µl rostral and 0.5 µl caudal to the laryngeal nerve branch.

Related Products: CCK-SAP (Cat. #IT-31), Saporin (Cat. #PR-01)

Suarez AN, Hsu TM, DeLartigue G, Kanoski SE (2017) Gastrointestinal vagal afferent signaling promotes hippocampal-dependent memory function in rats. Neuroscience 2017 Abstracts 510.22 / PP13. Society for Neuroscience, Washington, DC.

Summary: The vagus nerve is the primary conduit of communication between feeding-relevant gastrointestinal (GI) signals and the brain. Vagally-mediated GI satiation signals, including gastric distension and intra-gastric nutrient infusion, activate neurons in the hippocampus (HPC) through unidentified polysynaptic pathways. The functional relevance of GI-derived communication to the HPC is unknown. Here we first explored whether chronic disruption of gut-to-brain vagal tone via subdiaphragmatic vagotomy (SDV) negatively impacts HPC-dependent memory function in rats. While SDV did not impair HPC-dependent appetitive learning based on interoceptive energy status cues or social food-related cues, SDV did impair spatial working memory (Barnes maze) and contextual episodic memory (novel object in context; NOIC), two HPC-dependent tasks that involve processing of visuospatial stimuli. Next, to determine whether vagal sensory/afferent vs. motor/efferent signaling regulates HPC-dependent memory function, we employed a novel approach in which a saporin conjugated to cholecystokinin (CCK-SAP) or an unconjugated control saporin is injected into the nodose ganglia, a strategy that preserves 100% of vagal efferent signaling while eliminating ~80% of GI-derived vagal afferent signaling. Similar to SDV rats, CCK-SAP rats were impaired in both the Barne’s maze task and NOIC learning relative to controls. Consistent with the memory deficits, immunoblot protein analyses in hippocampus lysates revealed reduced neurotophic [brain- derived neurotrophic factor (BDNF)], and neurogenesis [doublecortin (DCX)] markers in both SDV and CCK-SAP rats relative to controls. These findings indicate that GI-derived vagal afferent signaling is critical in regulating HPC-dependent mnemonic function. Results have direct clinical relevance, as procedures that chronically disrupt vagus nerve signaling (e.g., vBloc) have recently been FDA-approved for obesity treatment.

Related Products: CCK-SAP (Cat. #IT-31)

Diepenbroek C, Quinn D, Stephens R, Zollinger B, Anderson S, Pan A, de Lartigue G (2017) Validation and characterization of a novel method for selective vagal deafferentation of the gut. Am J Physiol Gastrointest Liver Physiol 313:G342-G352. doi: 10.1152/ajpgi.00095.2017

Objective: To develop a new method that allows targeted lesioning of vagal afferent neurons that innervate the upper GI tract while sparing vagal efferent neurons.

Summary: CCK-SAP ablates a subpopulation of VAN in culture. In vivo, CCK-SAP injection into the NG reduces VAN innervating the mucosal and muscular layers of the stomach and small intestine but not the colon, while leaving vagal efferent neurons intact.

Usage: In vitro: each well was treated with a different dose of saporin conjugates (0, 2.4, 24, or 240 ng) for 24 h. In vivo: An equal volume (rat: 1 µl; mouse: 0.5 µl) of CCK-SAP (250 ng/µl) or Saporin (250 ng/µl) was injected at two sites rostral and caudal to the laryngeal nerve branch.

Related Products: CCK-SAP (Cat. #IT-31)