targeted-toxins

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.

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 163(2):149-167. doi: 10.1111/jnc.15683 PMID: 35921478

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.