targeted-toxins

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)

Zlatkovic J, Dalmau Gasull A, Hägg D, Font-Gironès F, Bellman J, Meister B, Palsdottir V, Ruud J, Ohlsson C, Dickson SL, Anesten F, Jansson JO (2023) Reduction of body weight by increased loading is associated with activation of norepinephrine neurones in the medial nucleus of the solitary tract. J Neuroendocrinol 35(12):e13352. doi: 10.1111/jne.13352 PMID: 37885347

Objective: To show that the feed-back regulation of body weight, initiated by a novel leptin-independent body weight homeostat, involves a CNS mechanism

Summary: In conclusion, increased load appears to reduce body weight and food intake via activation of norepinephrine neurones in the medial nucleus of the solitary tract.

Usage: 5 ng of Anti-DBH-SAP (IT-03) was bilaterally injected into the NTS in Male C57/B6J mice and Sprague–Dawley rats.

Related Products: Anti-DBH-SAP (Cat. #IT-03)

Gamage R, Rossetti I, Niedermayer G, Münch G, Buskila Y, Gyengesi E. (2023) Chronic neuroinflammation during aging leads to cholinergic neurodegeneration in the mouse medial septum. J Neuroinflammation 20(1):235. doi: 10.1186/s12974-023-02897-5 PMID: 37833764

Summary: This publication presents the findings of studies on age-related cholinergic decline. The authors mention a diffusion MRI study that documented a 25% reduction in the BFCN (Basal Forebrain Cholinergic Neurons) population and a significant loss of terminal cholinergic projections in the hippocampus after inducing selective BFCN degeneration in mice using mu p75-SAP.

Related Products: mu p75-SAP (Cat. #IT-16)

See Also:

• Kerbler GM et al. Diffusion-weighted magnetic resonance imaging detection of basal forebrain cholinergic degeneration in a mouse model. Neuroimage 66C:133-141, 2013.

Münzberg H, Berthoud HR, Neuhuber WL (2023) Sensory spinal interoceptive pathways and energy balance regulation. Mol Metab 78:101817. doi: 10.1016/j.molmet.2023.101817 PMID: 37806487

Objective: To review and discuss the roles of spinal sensory pathways, specifically dorsal root ganglia (DRG) afferents, in energy balance regulation, highlighting their contributions to metabolic homeostasis in health and disease.

Summary: This comprehensive review explores the emerging significance of spinal sensory neurons, beyond traditional gut-brain and adipose tissue-to-brain signaling pathways, in regulating energy intake and metabolism. It delves into the anatomy and functions of spinal sensory pathways, emphasizing the potential of DRG afferents in providing metabolic information to the brain. The review suggests that identifying specific DRG neurons and understanding their molecular mechanisms are crucial steps toward developing targeted therapies for metabolic diseases, such as obesity, diabetes, and cancer.

Usage: The publication references that CCK-SAP (IT-31) injected into the nodose ganglia of mice and rats selectively ablates vagal afferent neurons expressing CCKA receptors.

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.

Campideli-Santana AC, da Costa Silva KS, Araújo-Lopes R, Antunes LM, Szawka RE (2023) Submaximal loss of KNDy neurons accelerates and amplifies pulsatile LH secretion in female rats. J Endocrine Society 7(S1):bvad114.1214. doi: 10.1210/jendso/bvad114.1214

Objective: To investigate the impact of the submaximal loss of KNDy neurons on the pulsatile secretion of luteinizing hormone (LH) in female rats.

Summary: The study found that a partial loss of these neurons led to irregular estrous cycles and increased frequency and amplitude of LH pulses. This suggests a new role for KNDy neurons in moderating LH pulse frequency and amplitude in ovary-intact animals, with implications for early antral follicle recruitment.

Usage: Adult female rats underwent a neurochemical ablation of KNDy neurons via intra-ARC stereotaxic injections of NKB-SAP (IT-63), while control animals received Blank-SAP (IT-21).

Related Products: NKB-SAP (Cat. #IT-63), Blank-SAP (Cat. #IT-21)

Aquino NSS, Campideli-Santana AC, Antunes LM, Araújo-Lopes R, da Costa Silva KS, Costa Henriques P, de Oliveira Gusmão D, Bernuci MP, Szawka RE, dos Reis AM (2023) Partial loss of KNDy neurons in prenatally androgen treated female rats alters the LH secretion and ovarian morphology in a model of polycystic ovary syndrome. J Endocrine Society 7(S1):bvad114.1215. doi: 10.1210/jendso/bvad114.1215

Objective: To examine the impact of partial loss of KNDy neurons in prenatally androgen-treated female rats on luteinizing hormone (LH) secretion and ovarian morphology, as a model of polycystic ovary syndrome (PCOS).

Summary: The study found that the ablation of KNDy neurons resulted in increased LH pulse amplitude and mean LH levels without affecting pulse frequency, and partially restored the number of primordial follicles, suggesting KNDy neurons’ role in modulating LH release and ovarian reserve in PCOS.

Usage: Intra-ARC stereotaxic injections of the neurokinin-3 receptor agonist conjugated with Saporin (NKB-SAP, IT-63) to induce the lesion of KNDy neurons. Blank-SAP (IT-21) was used as a control.

Related Products: NKB-SAP (Cat. #IT-63), Blank-SAP (Cat. #IT-21)