targeted-toxins

Fulton S, Horn CC, Zhang C (2024) Characterizing a new tool to manipulate area postrema GLP1R+ neurons across species. Physiol Behav 114474. doi: 10.1016/j.physbeh.2024.114474 PMID: 38272107

Objective: Characterize the ligand exenatide conjugated to saporin as a tool to ablate GLP1 receptor-expressing cells from human, mice, and shrews, a small animal model capable of emesis (vomiting).

Summary: Nausea is a distressing sensation that is a common side effect of many medications. Nausea and emesis are among the top adverse side effects of glucagon-like peptide-1 (GLP1) receptor (GLP1R) agonists-based medications to treat type 2 diabetes and obesity. The area postrema is a brain structure that mediates nausea effects. The authors provide characterization of Ex4-SAP (GLP-1-SAP) to specifically ablate GLP1R-expressing HEK293T cells in vitro and in area postrema neurons in mice and house musk shrews in vivo.

Usage: C57BL-6J mice were injected with Ex4-SAP (IT-90) or Blank-Streptavidin-SAP at 200 ng/ul, in a total of 400 nl at a rate of 2 nl/second. Musk shrews were injected with Ex4-SAP (IT-90) or Blank-Streptavidin-SAP at 500 ng/ul, in a total of 200 nl at a rate of 2 nl/second.

Related Products: Ex4-SAP (GLP-1-SAP) (Cat. #IT-90), Blank-Streptavidin-SAP (Cat. #IT-27B)

Janes TA, Cardani S, Saini JK, Pagliardini S (2024) Etonogestrel promotes respiratory recovery in an in vivo rat model of central chemoreflex impairment. Acta Physiol (Oxf) e14093. doi: 10.1111/apha.14093 PMID: 38258900

Objective: Examine the use of progestins and synthetic progestins in the stimulation of breathing, especially after chemoreflexive impairment.

Summary: Central CO2 chemoreflex is important for respiratory control. The retrotrapezoid nucleus is involved in CO2 chemosensitivity where its removal or inhibition attenuates CO2 chemoreflexes and diminishes restful breathing. Progesterone stimulates restful breathing and CO2 chemoreflexes. The authors investigated whether acute or chronic administration of the progestinic drug, etonogestrel, could help in the recovery of respiratory chemoreflexes following lesion of the retrotrapezoid nucleus via a SP-SAP.

Usage: Rats were injected with 26-43.3 ng/ul of SP-SAP (IT-11) or 46.7 ng/ul of Blank-SAP (IT-21), with 150 nl per injection.

Related Products: SSP-SAP (Cat. #IT-11), Blank-SAP (Cat. #IT-21)

Donovan LJ, Bridges CM, Nippert AR, Wang M, Wu S, Forman TE, Haight ES, Huck NA, Bond SF, Jordan CE, Gardner AM, Nair RV, Tawfik VL (2024) Repopulated spinal cord microglia exhibit a unique transcriptome and contribute to pain resolution. Cell Rep 43(2):113683. doi: 10.1016/j.celrep.2024.113683 PMID: 38261512

Objective: To study the role of microglia in pain resolution and determine if repopulated microglia actively resolve pain or initiate the transition from acute to chronic pain.

Summary: Pain resolution coincides with microglial repopulation in the spinal cord rather than depletion. Repopulated microglia exhibit unique gene expressions related to phagocytosis and stress response in mice. The study identified potential targets for developing microglial-targeted pain therapeutics by comparing mouse and human spinal cord microglial datasets.

Related Products: Mac-1-SAP mouse/human (Cat. #IT-06)

See Also:

• Echeverry S et al. Spinal microglia are required for long-term maintenance of neuropathic pain. Pain 158:1792-1801, 2017.
• Sorge R et al. Different immune cells mediate mechanical pain hypersensitivity in male and female mice. Nat Neurosci 18:1081-1083, 2015.

Masmudi-Martín M, López-Aranda MF, Navarro-Lobato I, Khan ZU (2024) A role of frontal association cortex in long-term object recognition memory of objects with complex features in rats. Eur J Neurosci 59(7):1743-1752. doi: 10.1111/ejn.16243 PMID: 38238909

Objective: Provide evidence that the frontal association cortex and not the Perirhinal cortex is essential for object recognition memory (ORM) of objects with complex features.

Summary: The Perirhinal cortex is a brain area that has been seen as being crucial for ORM. However, the authors challenge that thought by using an ORM enhancer named RGS14414. Used as a tool, expression of it in rat brain frontal association cortex induced the formation of long-term complex ORM whereas the expression of the enhancer in Perirhinal cortex didn’t illicit the same effect. The authors also showed that expression of the enhancer in Perirhinal cortex instead caused formation of ORM of objects with only simple features. Furthermore, the selective elimination of frontal association cortex neurons via OX7-SAP (IT-02) completely removed the formation of complex ORM.

Usage: OX7-SAP (IT-02) was injected into the frontal association cortex of rats at a dose of 0.2 ug in 1 ul.

Related Products: OX7-SAP (Cat. #IT-02)

Maiarù M, Leese C, Silva-Hucha S, Fontana-Giusti S, Tait L, Tamagnini F, Davletov B, Hunt SP (2024) Substance P-botulinum mediates long-term silencing of pain pathways that can be re-instated with a second injection of the construct in mice. J Pain 25(6):104466. doi: 10.1016/j.jpain.2024.01.331 PMID: 38218509

Summary: The authors discuss how Substance P-Botulinum is used to try to replicate the permanent results achieved with Substance P-Saporin (SP-SAP, SSP-SAP).

Related Products: SSP-SAP (Cat. #IT-11)

See Also:

• Mantyh PW et al. Inhibition of hyperalgesia by ablation of lamina I spinal neurons expressing the substance P receptor. Science 278:275-279, 1997.
• Nichols ML et al. Transmission of chronic nociception by spinal neurons expressing the substance P receptor. Science 286:1558-1561, 1999.
• Brown DC et al. Intrathecal substance p-saporin in the dog: efficacy in bone cancer pain. Anesthesiology 119(5):1178-1185, 2013.
• Wiley RG et al. Anti-nociceptive effects of selectively destroying substance P receptor-expressing dorsal horn neurons using [Sar(9),Met(O(2))(11)]-substance P-saporin: Behavioral and anatomical analyses. Neuroscience 146:1333-1345, 2007.
• Vierck CJ et al. Comparison of operant escape and innate reflex responses to nociceptive skin temperatures produced by heat and cold stimulation of rats. Behav Neurosci. 2004;118(3):627-35.

Ivanova D, O’Byrne KT (2024) New methods to investigate the GnRH pulse generator. J Mol Endocrinol 72(2):e230079. doi: 10.1530/JME-23-0079 PMID: 38085702

Objective: To review the latest methodologies and insights into the GnRH pulse generator and its role in regulating reproductive hormone secretion.

Summary: The paper discusses recent advancements in understanding the GnRH pulse generator and its role in reproductive hormone secretion. It highlights the involvement of kisspeptin/neurokinin B/dynorphin (KNDy) neurons and the use of advanced techniques like genetic mouse models, electrophysiology, optogenetics, and calcium imaging. These findings enhance our comprehension of the KNDy network’s oscillatory behavior and its regulation by gonadal steroids, which is crucial for developing better infertility treatments.

Related Products: NKB-SAP (Cat. #IT-63)

See Also:

• Helena C et al. KNDy neurons modulate the magnitude of the steroid-induced luteinizing hormone surges in ovariectomized rats. Endocrinology 156:4200-4213, 2015.

McDougle M, de Araujo A, Singh A, Yang M, Braga I, Paille V, Mendez-Hernandez R, Vergara M, Woodie LN, Gour A, Sharma A, Urs N, Warren B, de Lartigue G (2024) Separate gut-brain circuits for fat and sugar reinforcement combine to promote overeating. Cell Metab 36:1-15. doi: 10.1016/j.cmet.2023.12.014 PMID: 38242133

Objective: To investigate the separate gut-brain circuits for sugar and fat reinforcement and their combined effect on overeating.

Summary: This study reveals that intestinal fats and sugars are sensed by distinct vagal populations, each engaging separate central reward circuits to cause dopamine release and reinforcement. Combining fat and sugar triggers both circuits, leading to increased dopamine efflux and promoting overeating, highlighting a subconscious drive to consume obesogenic diets.

Usage: 0.5 µl of CCK-SAP (IT-31) or Blank-SAP as a negative control (IT-21) were injected bilaterally into the nodose ganglion for selective vagal deafferentation of the upper GI tract of mice.

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

de Paula FS (2023) Immunomodulatory impact of memory T lymphocyties in periodontitis. Univ Minnesota Thesis.

Objective: This thesis paper sought to determine whether local reactivation of oral tissue resident memory cells (TRM) of a defined antigen specificity could exacerbate ligature-induced periodontal (LIP), a model for periodontal disease in mice.

Summary: Reactivation of oral TRM aggravated alveolar bone loss and amplified gingival and cervical lymph node (cLN) inflammation. Furthermore, oral TRM reactivation enhanced transcriptional changes in pro-inflammatory and periodontitis-related genes. Therapeutic depletion of CD103-expressing oral TRM in advanced of LIP mitigated alveolar bone loss and associated gingiva and cLN inflammation. The study provides evidence that local reactivation of oral TRM can potentiate periodontitis.

Usage: Anti-CD103-SAP (IT-50) was administered in mice via i.p. injection (7 ug in PBS).

Related Products: Anti-CD103-SAP (Cat. #IT-50)

Loftén A, Adermark L, Ericson M, Söderpalm B (2023) Regulation of ethanol-mediated dopamine elevation by glycine receptors located on cholinergic interneurons in the nucleus accumbens. Addict Biol 28(12):e13349. doi: 10.1111/adb.13349 PMID: 38017639

Objective: The aim of this study was to explore the role of glycine receptors (GlyRs) on cholinergic interneurons (CIN) in sustaining extracellular dopamine levels and in ethanol-induced dopamine release.

Summary: Alcohol use disorder is one of the major psychiatric disorders worldwide. Ethanol reward is one of the many factors contributing to the disorder. The rewarding and reinforcing properties of ethanol have been linked to activation of the mesolimbic dopamine system, an effect that involves glycine receptors (GlyRs) in the nucleus accumbens. The study suggests that CIN are not important for GlyR-mediated regulation of basal dopamine output, but that CIN ablation blunts the ethanol-induced dopamine release by reducing the release of GlyR agonists.

Usage: CIN were ablated by Anti-ChAT-SAP administered locally in the nucleus accumbens of male Wistar rats. Rabbit-IgG-SAP was used as a control. Microinfusion was performed unilaterally into the nAc at a concentration of 0.5 ug/ul at 0.05 ul/min for 10 min for a total of 0.5 ul.

Related Products: Anti-ChAT-SAP (Cat. #IT-42), Rabbit IgG-SAP (Cat. #IT-35)

Takanami K, Kuroiwa M, Ishikawa R, Imai Y, Oishi A, Hashino M, Shimoda Y, Sakamoto H, Koide T (2023) Function of gastrin-releasing peptide receptors in ocular itch transmission in the mouse trigeminal sensory system. Front Mol Neurosci 16:1280024. doi: 10.3389/fnmol.2023.1280024 PMID: 38098939

Objective: To investigate the role of gastrin-releasing peptide (GRP) and GRP receptor (GRPR) in itch transmission in the spinal somatosensory system, and to determine whether the GRP system is involved in itch neurotransmission of the eyes in the trigeminal sensory system

Summary: Administering itch mediators like histamine (His) and chloroquine (CQ) caused high levels of eye scratching in a concentration-dependent manner, with significant gender differences observed for His. Histological studies showed that His and CQ significantly activated GRPR-expressing neurons in a specific brain region of transgenic mice. Blocking these neurons with a GRPR antagonist or eliminating them reduced CQ-induced scratching. Injecting a GRPR agonist without an itch stimulus led to excessive facial scratching, indicating the central role of GRPR neurons in mediating itch responses.

Usage: 500 ng Blank-SAP (IT-21) or 500 ng Bombesin-SAP (IT-40) were intracisternally administered (5-uL volume) 2 weeks prior to behavioral experiments.

Related Products: Bombesin-SAP (Cat. #IT-40), Blank-SAP (Cat. #IT-21)