control-conjugates

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: SP-SAP (Cat. #IT-07), Blank-SAP (Cat. #IT-21)

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)

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)

Goodman RL, Moore AM, Onslow K, Hileman SM, Hardy SL, Bowdridge EC, Walters BA, Agus S, Griesgraber MJ, Aerts EG, Lehman MN, Coolen LM (2023) Lesions of kndy and kiss1r neurons in the arcuate nucleus produce different effects on lh pulse patterns in female sheep. Endocrinology 164(11):bqad148. doi: 10.1210/endocr/bqad148 PMID: 37776515

Objective: To test the functional role of ovine KNDy neurons in pulse generation and identify the roles of nearby Kiss1 receptor (Kiss1R)-containing cells.

Summary: Injection of NK3-SAP (NKB-SAP) ablated over 90% of the KNDy cells, Kiss-SAP lesioned about two-thirds of the Kiss1R population. This led to a significant decrease in LH pulse amplitude and altering LH pulse patterns. NK3-SAP increased the interpulse interval without affecting the regularity of LH pulses, whereas Kiss-SAP disrupted their regular hourly occurrence but not the interpulse interval. The findings suggest that KNDy neurons are critical for GnRH pulse generation in ewes, while ARC Kiss1R cells support the amplitude and regularity of these pulses, possibly as part of a positive feedback loop involving GABA or glutamate.

Usage: Saporin conjugates were injected into the arcuate nucleus. Kiss-SAP (kisspeptin54-SAP) was diluted to 700 ng/μL in PBS immediately before use. In preliminary work to test the effectiveness of Kiss-SAP, a single unilateral injection (1 μL of 700 ng/μL) of this conjugate was made in the preoptic area of 3 ewes. The contralateral side was used as control and either received no injections or Blank-SAP (1 μL of 700 ng/μL) (IT-21).

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

Harris RBS (2023) Low dose peripheral leptin infusion produces selective activation of ventromedial hypothalamic and hindbrain STAT3. Am J Physiol Endocrinol Metab doi: 10.1152/ajpendo.00083.2023 PMID: 37285599

Objective: To show that the deletion of leptin-receptor expressing cells in the ventromedial hypothalamus (VMH) has no effect on basal body weight or body fat mass, but greatly attenuates the inhibition of food intake.

Summary: This study evaluates leptin’s impact on hypothalamic pSTAT3 in leptin-infused versus injected rats. High-dose leptin suppressed food intake and reduced weight and fat mass without affecting energy metrics, with pSTAT3 increases observed in the VMH only during intake suppression and in the nucleus of the solitary tract over both short and extended periods. These results highlight the role of VMH and hindbrain receptors in mediating leptin’s effects on food intake and metabolic changes.

Usage: Leptin-SAP is referenced in Seamon et al 2019: Male Sprague-Dawley rats received bilateral VMH 75 nl injections of 260 ng/microliter of Leptin-SAP (IT-47) or Blank-Saporin (IT-21).

Related Products: Leptin-SAP (Cat. #IT-47), Blank-SAP (Cat. #IT-21)

See Also:

• Seamon M et al. Leptin receptor-expressing neurons in ventromedial nucleus of the hypothalamus contribute to weight loss caused by fourth ventricle leptin infusions. Am J Physiol Endocrinol Metab 317(4):E586-E596, 2019.

Chen CH, Tsai TC, Wu YJ, Hsu KS (2023) Gastric vagal afferent signaling to the basolateral amygdala mediates anxiety-like behaviors in experimental colitis mice. JCI Insight e161874. doi: 10.1172/jci.insight.161874 PMID: 37200091

Objective: This study aimed to characterize gut-to-brain signaling and brain circuitry responsible for anxiety-like behaviors in a mouse model of inflammatory bowel disease.

Summary: The researchers found that mice with experimental colitis induced by dextran sulfate sodium administration displayed increased anxiety-like behaviors, which were prevented by cutting the vagus nerve connecting the gut to the brain. Further experiments showed that silencing brain cells in the locus coeruleus that project to the basolateral amygdala reduced anxiety behaviors in the colitis mice.

Usage: CCK-SAP (250 ng/µl) or Blank-SAP (250 ng/µl) were unilaterally or bilaterally injected to rostral (0.5 µl) and caudal (0.5 µl) parts of the nodose ganglia using a beveled injection pipette controlled by a microprocessor-controlled injector at the speed of 50 nl/sec.

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

Zhou XA, Ngiam G, Qian L, Sankorrakul K, Coulson EJ, Chuang KH (2022) The basal forebrain volume reduction detected by MRI does not necessarily link with the cholinergic neuronal loss in the Alzheimer’s disease mouse model. Neurobiol Aging 117:24-32. doi: 10.1016/j.neurobiolaging.2022.03.017 PMID: 35640461

Objective: Assess basal forebrain (BF) cholinergic neuron number by histological counts and compare with the volume measurements from an in vivo MRI Alzheimer’s disease (AD) mouse model.

Summary: Degeneration of cholinergic neurons in the BF contributes to cognitive impairment in AD. A decrease of BF volume measured by structural MRI is thought to represent loss of cholinergic neurons. As there are various types of neurons in the BF, whether this MRI measurement actually reflects the change of cholinergic neurons has not been verified. To test whether specific loss of cholinergic neurons results in BF reduction, the authors ablated cholinergic neurons in the Medial septum.

Usage: Lesions were made via injections of mu-p75-SAP (0.5 mg/ml) or control Rabbit-IgG-SAP (0.5 mg/mL) into ten-week-old female C57Bl/6J mice. However, there was no detectable change in MRI volume between lesioned and unlesioned mice. The results indicate that although loss of cholinergic neurons within the BF likely contribute to volume loss, this change in volume cannot be taken as a direct biomarker of cholinergic neuron number.

Related Products: mu p75-SAP (Cat. #IT-16), Rabbit IgG-SAP (Cat. #IT-35)