targeted-toxins

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.

Madrid LI, Bandhavkar S, Hafey K, Jimenez-Martin J, Milne M, Coulson EJ, Jhaveri DJ (2022) Stimulation of the muscarinic receptor M4 activates quiescent neural precursor cells and ameliorates medial septum cholinergic lesion-induced impairments in adult hippocampal neurogenesis. bioRxiv 2022.08.25.505357. doi: 10.1101/2022.08.25.505357

Objective: To investigate the contribution of basal forebrain medial septum (MS) and diagonal band of Broca (DBB) cholinergic neurons that innervate the hippocampus and the identity of the cholinergic receptor(s) that regulate the production and maturation of new neurons.

Summary: This work reveals stage-specific roles of cholinergic signaling in regulating functionally relevant adult hippocampal neurogenesis.

Usage: Medial septum cholinergic lesion was achieved by infusion of mu p75-SAP (0.4 µg/µl). Rabbit IgG-SAP (0.4 µg/µl) was used as control.

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

Imado E, Sun S, Abawa AR, Tahara T, Kochi T, Huynh TNB, Asano S, Hasebe S, Nakamura Y, Hisaoka-Nakashima K, Kotake Y, Irifune M, Tsuga K, Takuma K, Morioka N, Kiguchi N, Ago Y (2022) Prenatal exposure to valproic acid causes allodynia associated with spinal microglial activation. Neurochem Int 160:105415. doi: 10.1016/j.neuint.2022.105415

Objective: To further understand the mechanism underlying sensory phenotypes in autism spectrum disorder (ASD).

Summary: The authors investigated the age-dependent tactile sensitivity in an animal model of ASD induced by prenatal exposure to valproic acid and subsequently assessed the involvement of microglia in the spinal cord in pain processing.

Usage: To deplete microglia in the spinal cord, Mac-1-SAP (11.2 μg/5.5 μl) was injected intrathecally at the level of L4–L5 in adult (8-week-old) mice.

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

Llorente-Ovejero A, Bengoetxea de Tena I, Martínez-Gardeazabal J, Moreno-Rodríguez M, Lombardero L, Manuel I, Rodríguez-Puertas R (2022) Cannabinoid receptors and glial response following a basal forebrain cholinergic lesion. ACS Pharmacol Transl Sci 5(9):791-802. doi: 10.1021/acsptsci.2c00069 PMID: 36110372

Objective: The endocannabinoid system is involved in the control of learning, memory, and neuroinflammatory processes and plays a role in neurodegeneration, such as in Alzheimer’s disease (AD). The objective was to study the roles of cannabinoid receptors in the regulation of neuroinflammation.

Summary: Selective agonists and antagonists to the cannabinoid receptors CB1 and CB2 were studied for their binding to G-proteins after specific lesioning of the basal forebrain cholinergic neurons (BCFN) using 192-IgG-SAP. These neurons are the same cholinergic pathways that are lost in the early stages of Alzheimer’s disease (AD). In their study, an increase of microglia immunoreactivities (GFAP and Iba-1) and decrease of astrocyte immunoreactivities were seen which indicate microglia-mediated neuroinflammation. In cortical BFCN projection areas, CB1 receptor binding to Gi/o-proteins was upregulated and at the injection site, the area that showed the highest increase of microglia, only slight CB2 binding to Gi/o-proteins were detected. Dose: Rats received 135 ng/μLof 192IgG-saporin (1μL/hemisphere; 0.25μL/min).

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

Orciani C, Hall H, Pentz R, Foret MK, Do Carmo S, Cuello AC (2022) Long-term nucleus basalis cholinergic depletion induces attentional deficits and impacts cortical neurons and BDNF levels without affecting the NGF synthesis. J Neurochem doi: 10.1111/jnc.15683

Objective: To determine whether reciprocal interaction of basal forebrain cholinergic neurons (BFCN) impact neurotrophin availability and affect cortical neuronal markers.

Summary: There is a neuroprotective role of cholinergic neurotransmission in the adult, fully-differentiated cortex.

Usage: Immunolesioned BFCN projecting mainly to the cortex with 192-IgG-SAP (bilateral 0.5 ug/ul; 1.0 ul/hemisphere) in 2.5 month-old Wistar rats.

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

Akmese C, Sevinc C, Halim S, Unal G (2022) Differential role of GABAergic and cholinergic ventral pallidal neurons in behavioral despair, conditioned fear memory and active coping. bioRxiv 2022.07.21.500949. doi: 10.1101/2022.07.21.500949

Related Products: 192-IgG-SAP (Cat. #IT-01), GAT1-SAP (Cat. #IT-32)

Grady FS, Boes AD, Geerling JC (2022) A century searching for the neurons necessary for wakefulness. Front Neurosci 16:930514. doi: 10.3389/fnins.2022.930514

Objective: This review article attempts to summarize research that has investigated the neurons necessary for wakefulness.

Summary: The authors summarize animal experiments and research performed in different brain regions to further understand wakefulness. Several saporin conjugates are discussed.

Usage: Lesions of the basal forebrain were done by injecting a 0.1% solution of either 192-IgG-SAP or Orexin-SAP at four different sites (Fuller et al. and Geraschenko et al.); Intraventricular injection of Anti-DBH-SAP (Gompf et al.); Bilateral injections of 192-IgG-SAP (Kaur et al.).

Related Products: Orexin-B-SAP (Cat. #IT-20)

See Also:

• Fuller P et al. Reassessment of the structural basis of the ascending arousal system. J Comp Neurol 519(5):933-956, 2011.
• Gerashchenko D et al. Insomnia following hypocretin2-saporin lesions of the substantia nigra. Neuroscience 137(1):29-36, 2006.
• Gompf HS et al. Locus ceruleus and anterior cingulate cortex sustain wakefulness in a novel environment. J Neurosci 30(43):14543-14551, 2010.
• Kaur S et al. Effects of ibotenate and 192IgG-saporin lesions of the nucleus basalis magnocellularis/substantia innominata on spontaneous sleep and wake states and on recovery sleep after sleep deprivation in rats. J Neurosci 28:491-504, 2008.

Q: What are neuropeptide-toxins and how do they work?

A: Neuropeptide-toxin conjugates are made up of the ribosome-inactivating protein, saporin, coupled to a naturally-occurring or synthetically-modified neuropeptide such as Substance P or dermorphin. The conjugate has binding specificity similar to the native, unconjugated neuropeptide. When the neuropeptide binds to its cognate receptor, the conjugate is internalized. Once inside the target cell within an endosome, the neuropeptide and saporin separate and some of the saporin translocates into the cytoplasm where it catalytically inactivates ribosomes resulting in cell death.

Q: Are neuropeptide-toxins effective suicide transport agents?

A: The general answer to this question is not currently known. However, in the instance of intrathecally injected dermorphin-SAP (Cat. #IT-12), the evidence does NOT favor suicide transport of the neuropeptide-toxin conjugate. When supramaximal doses of dermorphin-SAP (750 ng) are injected into the lumbar subarachnoid space of adult rats, less than 1% of lumbar dorsal root ganglion cells show evidence of saporin activity. This is in spite of the fact that many of these neurons express the targeted mu opioid receptor on their central terminals in the superficial dorsal horn of the spinal cord. This assertion is based on analysis of over 16,000 neurons from dorsal root ganglia in six rats.

See: Targeted Toxins

Alhassan M (2022) Sensory and motor visual functions in Parkinson’s Disease with respect to freezing of gait symptoms. J Ophthalmol & Vis Sci 7(2):1069.

Objective: This review article summarizes the results from previous studies focusing on visual functions in Parkinson’s Disease patients.

Summary: Freezing of gait (FOG) is considered to be a motor disorder symptom that affects some Parkinson Disease (PD) patients; however, it is hypothesized that sensory systems may also be involved in FOG. Visual functions include high contrast visual acuity, low contrast visual acuity, contrast sensitivity, Vernier acuity, mesopic vision, stereopsis, motion perception, and vergence eye movements and are all affected in PD patients with FOG patients having more deficits in some of these functions. FOG patients also had impairments in non-dopaminergic mediated functions which suggests greater impairment in two functions that involve cholinergic neurotransmitters. 192-IgG-SAP (Cat. IT-01) was used to create a PD rat animal model to study the contribution of the cholinergic system to motor functions. It was found that the fall rates were more frequent in rats, that were injected with dual 192 IgG-saporin /6-hydroxydopamine (6-OHDA) than rats with either isolated cholinergic or isolated dopaminergic lesions.

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

See Also:

• Kucinski A et al. Modeling fall propensity in Parkinson’s disease: deficits in the attentional control of complex movements in rats with cortical-cholinergic and striatal-dopaminergic deafferentation. J Neurosci 33(42):16522-16539, 2013.

Levine AS, Jewett DC, Kotz CM, Olszewski PK (2022) Behavioral plasticity: Role of neuropeptides in shaping feeding responses. Appetite 174:106031. doi: 10.1016/j.appet.2022.106031 PMID: 35395362

Objective: Review studies on feeding behavior involving neuropeptides that influence behavioral plasticity – primarily opioids, orexin, neuropeptide Y, and oxytocin.

Summary: Eating behavior is influenced by a number of external factors, including time of day, type of food available, energy balance state, and stressors. The reviewed work underscores that environmental factors play a critical role in feeding behavior and energy balance, but changes in eating behavior also result from a multitude of non-environmental factors, such that there can be no single mechanism or variable that can explain ingestive behavior.

Usage: References a previous publication using Oxytocin-SAP (IT-46).

Related Products: Oxytocin-SAP (Cat. #IT-46)

See Also:

• Baskin DG et al. A new oxytocin-saporin cytotoxin for lesioning oxytocin-receptive neurons in the rat hindbrain. Endocrinology 151(9):4207-4213, 2010.