targeted-toxins

Leanza G, Zorec R (2023) Towards astroglia-based noradrenergic hypothesis of Alzheimer’s disease. Function (Oxf) 4(1):zqac060., IT. doi: 10.1093/function/zqac060 PMID: 36590326

Summary: These results indicate a prominent role of NA-neurons vs. ACh neurons in impairments of working memory, relevant for AD, and are consistent with an astrocyte-specific metabolic impairment in a mouse model of intellectual disability.

Usage: Bilateral icv injection of 192-IgG-SAP and/or Anti-DBH-SAP

Related Products: 192-IgG-SAP (Cat. #IT-01), Anti-DBH-SAP (Cat. #IT-03)

Fullerton E (2022) The impact of advanced age on morphine anti-hyperalgesia and the role of mu opioid receptor signaling in the periaqueductal gray of male and female rats. Georgia State University Thesis. doi: 10.57709/30509896

Objective: To investigate the impact of advanced age on the antihyperalgesic effect of morphine, as well as its association with changes in μ-opioid receptor expression and binding in the rat midbrain Periaqueductal Gray (PAG) in both male and female rats.

Summary: This study examined the effects of advanced age on the antihyperalgesic properties of morphine and its relationship with mu-opioid receptor expression and binding in the rat midbrain Periaqueductal Gray (PAG). The findings revealed that advanced age attenuated the antihyperalgesic effect of morphine, accompanied by a decrease in mu-opioid receptor expression and binding in the PAG of both male and female rats, suggesting age-related alterations in opioid signaling that may contribute to reduced analgesic efficacy in older individuals.

Related Products: Dermorphin-SAP / MOR-SAP (Cat. #IT-12)

Maunze B (2022) Pituitary adenylate cylase-activating polypeptide receptor: Multiple signaling pathways involved in energy homeostasis. Marquette University Dissertations 1212. Thesis.

Objective: To determine the endogenous role of pituitary adenylate cyclase activating polypeptide (PACAP) in affecting the ventromedial nuclei (VMN) of the hypothalamus and its control of feeding and energy expenditure through the Type I PAC1 receptor (PAC1R).

Summary: VMN cells expressing PAC1 receptors in Male Sprague Dawley rats were knocked down via injection of Saporin or PACAP-SAP and trafficking also pharmacologically inhibited. This increased meal sizes, reduced total number of meals, and induced body weight gain. PACAP signaling replicates the effects of leptin administration in the VMN and appears to enable leptin regulation of energy homeostasis. Co-immunoprecipitation was used to show that VMN PAC1 and leptin receptors are found in the same cell, and they form an immunocomplex. Inhibiting downstream effectors of PACAP signaling, such as PKA and PKC, enhanced or prevented leptin signaling respectively. The current findings revealed that endogenous PACAP signaling in the VMN has a potent regulatory influence over both energy intake in the form of feeding, and energy output via thermogenesis and locomotor activity. Moreover, PACAP actions in the VMN share nearly identical secondary effects as with leptin administration in the same brain region suggesting that these two neuropeptides could functionally intersect.

Related Products: PACAP-SAP (Cat. #IT-84)

Yamamoto-Fukuda T, Akiyama N, Tatsumi N, Okabe M, Kojima H (2022) Keratinocyte growth factor stimulates growth of p75+ neural crest lineage cells during middle ear cholesteatoma formation in mice. Am J Pathol 192(11):1573-1591. doi: 10.1016/j.ajpath.2022.07.010 PMID: 36210210

Objective: To identify the role of neural crest (NC) lineage epithelial cells during cholesteatoma formation and to detect specific cell markers to identify these NC lineage epithelial cells in human cholesteatoma tissues.

Summary: Cholesteatoma is a pathologic condition associated with otitis media and is a gradually destructive epithelial tumor within the middle ear and temporal bone. NC lineage epithelium controls the homeostasis of the middle ear and plays a role in repairing otitis media. Keratinocyte growth factor (KGF) stimulates epithelial cell growth and is associated with the recurrence of cholesteatomas. Injections of the immunotoxin mu p75-SAP (Cat. #IT-16) into the cholesteatoma tissue eliminated p75-postitive NC cells and diminished the cholesteatoma. This helped demonstrate that NC lineages are the cellular origin of cholesteatoma and that p75 transcription under KGF is required for the development of cholesteatoma. Controlling p75 signaling may reduce the proliferation of NC cells and could represent a new therapeutic target for cholesteatoma.

Usage: 10 uL mu-p75-SAP (0.2 or 0.6 mg/mL) was injected into the cholesteatoma region or tympanic membrane.

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

Hoffman S, Alvares D, Adeli K (2022) GLP-1 attenuates intestinal fat absorption and chylomicron production via vagal afferent nerves originating in the portal vein. Mol Metab 65:101590. doi: 10.1016/j.molmet.2022.101590 PMID: 36067913

Objective: To examine the effect of vagal GLP-1 signaling on intestinal fat absorption and lipoprotein production.

Summary: Selective deafferentation of GLP-1R-containing nodose neurons with GLP-1R (Exenatide)-SAP caused significant increases in postprandial (but not fasting) plasma TG, plasma cholesterol, and TRL TG following an olive oil gavage. Over a 2-week period, increased food consumption and elevated liver lipids were also observed.

Usage: GLP-1R-SAP or Blank-SAP was administered to Syrian golden hamsters (bilateral nodose ganglia; 1 µg/1 µl).

Related Products: Ex4-SAP (GLP-1-SAP) (Cat. #IT-90), Blank-SAP (Cat. #IT-21)

Aikins AO, Little JT, Rybalchenko N, Cunningham JT (2022) Norepinephrine innervation of the supraoptic nucleus contributes to increased copeptin and dilutional hyponatremia in male rats. Am J Physiol Regul Integr Comp Physiol 323(5):R797-R809. doi: 10.1152/ajpregu.00086.2022 PMID: 36189988

Objective: Authors hypothesized that the A1/A2 noradrenergic neurons support chronic release of arginine vasopressin in cirrhosis leading to dilutional hyponatremia.

Summary: Dilutional hyponatremia associated with liver cirrhosis is due to inappropriate release of arginine vasopressin (AVP). The A1/A2 neurons stimulate the release of AVP from the supraoptic nucleus (SON) in response to nonosmotic stimuli. Injection of Anti-DBH-SAP (Cat. # IT-03) resulted in: 1) significantly reduced number of DBH immunoreactive A1/A2 neurons, 2) significantly reduced number of A1/A2 neurons immunoreactive to both DBH and Delta FosB positive neurons, 3) reduced number of SON neurons immunoreactive to both AVP and Delta FosB, 4) preventing the increase in plasma copeptin observed in vehicle-injected common bileduct (BDL) rats, and 5) normalizing plasma osmolality and hematocrit as compared with vehicle injection. The data suggest that A1/A2 neurons contribute to increased plasma copeptin and hypoosmolality in male BDL rats.

Usage: Bilateral injection of Anti-DBH-SAP into the supraoptic nucleus at (50 ng/500 nL)

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

Campideli-Santana AC, Gusmao DO, Almeida FRCL, Araujo-Lopes R, Szawka RE (2022) Partial loss of arcuate kisspeptin neurons in female rats stimulates luteinizing hormone and decreases prolactin secretion induced by estradiol. J Neuroendocrinol 34(11):e13204. doi: 10.1111/jne.13204 PMID: 36319592

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

Silva AR (2022) Uncovering central and peripheral pain mechanisms in Alzheimer’s disease. King’s College London Thesis.

Objective: To investigate alterations within the nociceptive pathways, under neuropathic pain conditions.

Summary: The data suggest a disrupted opioidergic tone in TASTPM mice, which followed by peripheral nerve injury, is mediated by peripheral immune cells.

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

See Also:

• Brightwell JJ et al. Noradrenergic neurons in the locus coeruleus contribute to neuropathic pain. Neuroscience 160:174-185, 2009.

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)

Lee W, Song G, Bae H (2022) Laminarin attenuates ros-mediated cell migration and invasiveness through mitochondrial dysfunction in pancreatic cancer cells. Antioxidants (Basel) 11(9):1714. doi: 10.3390/antiox11091714 PMID: 36139787

Objective: To determine the effects of laminarin on pancreatic cancer.

Summary: Laminarin showed synergistic effects when combined with 5-FU, a standard anticancer agent for pancreatic ductal adenocarcinoma (PDAC) with potential as a treatment for PDAC.

Usage: Lund et al. work on 5-FU resistant EMT-like pancreatic cancer cells are hypersensitive to photochemical internalization of the novel endoglin-targeting immunotoxin Anti-CD105-SAP.

Related Products: Anti-CD105-SAP (Cat. #IT-80)

See Also:

• Lund K et al. 5-FU resistant EMT-like pancreatic cancer cells are hypersensitive to photochemical internalization of the novel endoglin-targeting immunotoxin CD105-saporin. J Exp Clin Cancer Res 36(1):185, 2017.