targeted-toxins

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.

Zhang JJ, Song CG, Dai JM, Li L, Yang XM, Chen ZN (2022) Mechanism of opioid addiction and its intervention therapy: Focusing on the reward circuitry and mu-opioid receptor. MedComm 3(3):e148. doi: 10.1002/mco2.148 PMID: 35774845

Objective: To examine the mechanism of opioid addiction, with a specific focus on the reward circuitry and the role of the mu-opioid receptor, and to explore potential intervention therapies.

Summary: The authors discuss the neurobiological processes underlying addiction and highlight the importance of understanding these mechanisms in developing effective intervention therapies for opioid addiction.

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

See Also:

• Jenrette TA et al. Lesions of the patch compartment of dorsolateral striatum disrupt stimulus-response learning. Neuroscience 415:161-172, 2019.

Griffin JM, Healy FM, Dahal LN, Floisand Y, Woolley JF (2022) Worked to the bone: antibody-based conditioning as the future of transplant biology. J Hematol Oncol 15(1):65. doi: 10.1186/s13045-022-01284-6

Objective: To analyze the current status of antibody-based drugs in pre-transplant conditioning regimens and assess their potential in the future of transplant biology.

Summary: This review article suggests that antibody-based conditioning regimens may be the next big advancement in hematopoietic stem cell transplantation.

Related Products: Anti-CD117-SAP (Cat. #IT-83)

See Also:

• Palchaudhuri R et al. Non-genotoxic conditioning for hematopoietic stem cell transplantation using a hematopoietic-cell-specific internalizing immunotoxin. Nat Biotechnol 34:738-745, 2016.
• Castiello MC et al. Efficacy and safety of anti-CD45-saporin as conditioning agent for RAG deficiency. J Allergy Clin Immunol 147(1):309-320.e6, 2021.
• Czechowicz A et al. Selective hematopoietic stem cell ablation using CD117-antibody-drug-conjugates enables safe and effective transplantation with immunity preservation. Nat Commun 10:617, 2019.
• Li Z et al. Hematopoietic chimerism and donor-specific skin allograft tolerance after non-genotoxic CD117 antibody-drug-conjugate conditioning in MHC-mismatched allotransplantation. Nat Commun 10:616, 2019.

Krieger JP, Asker M, Van der Velden P, Börchers S, Richard JE, Maric I, Longo F, Singh A, De Larigue G, Skibicka KP (2022) Neural pathway for gut feelings: vagal interoceptive feedback from the gastrointestinal tract is a critical modulator of anxiety-like behavior. Biological Psychiatry in press. doi: 10.1016/j.biopsych.2022.04.020

Objective: To determine how the sensing of gastrointestinal state affects anxiety.

Summary: Vagal sensory signals from the gastrointestinal tract are critical for baseline and feeding-induced tuning of anxiety via the central amygdala in rats. The article results suggest vagal gut-brain signaling as a target to normalize interoception in anxiety.

Usage: 1.5 ul of CCK-SAP or Blank-SAP were delivered into each nodose ganglion at 250 ng/ul.

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

Bosecke C (2022) A novel anxiety process biomarker via electrovestibulography. University of Manitoba Thesis.

Objective: Use electrophysiological technique of Electrovestibulography to measure field potentials caused by vestibular neurons in the ear canal in order to identify biomarkers associated with anxiety disorder.

Summary: Anxiety disorders have no known biomarkers and are diagnosed based on symptoms. Identifying biomarkers could help improve the accuracy of anxiety disorder diagnosis, but can be difficult because the brain regions implicated in anxiety are very deep within the brain.

Usage: 192 IgG-SAP (Cat. #IT-01) was used to lesion the cholinergic medial septum inputs to the hippocampus. 192 IgG-saporin was diluted to 0.35 µg/µl with sterile saline, and 0.4 µl was infused bilaterally into each ventral site of the medial septum.

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