targeted-toxins

Mori A, Cross B, Uchida S, Kerrick Walker J, Ristuccia R (2021) How are adenosine and adenosine A2A receptors involved in the pathophysiology of amyotrophic lateral sclerosis?. Biomedicines 9(8):1027. doi: 10.3390/biomedicines9081027

Objective: To examine potential biomarkers and the acute symptomatic pharmacology, including respiratory motor neuron control, of adenosine A2A receptor antagonism, and to explore the potential of the A2A receptor as a target for Amyotrophic Lateral Sclerosis (ALS) therapy.

Summary: CTB-SAP is listed in a table of experimental animal models of ALS. Intrapleural CTB-SAP injected rats (neurotoxic model of respiratory motor neuron death).

See: Seven YB et al. Adenosine 2A receptor inhibition protects phrenic motor neurons from cell death induced by protein synthesis inhibition. Exp Neurol 323:113067, 2020.

Related Products: CTB-SAP (Cat. #IT-14)

Llorca-Torralba M, Camarena-Delgado C, Suárez-Pereira I, Bravo L, Mariscal P, Garcia-Partida JA, López-Martín C, Wei H, Pertovaara A, Mico JA, Berrocoso E (2022) Pain and depression comorbidity causes asymmetric plasticity in the locus coeruleus neurons. Brain 145(1):154-167. doi: 10.1093/brain/awab239

Summary: There is strong comorbidity between chronic pain and depression. This study explores how this comorbidity occurs. The authors refer to published research that shows icv administration of anti-DBH-SAP or intra-LC administration of lidocaine dampened the evoked pain in conditions of long-term nerve-injury. However, icv injection of anti-DBH-SAP disrupts all noradrenergic nuclei (A1-A7), some of which contribute to sensorial hypersensitivity.

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.
• Marques-Lopes J et al. The hyperalgesic effects induced by the injection of angiotensin II into the caudal ventrolateral medulla are mediated by the pontine A(5) noradrenergic cell group. Brain Res 1325:41-52, 2010.

Yue XF, Wang AZ, Hou YP, Fan K (2021) Effects of propofol on sleep architecture and sleep-wake systems in rats. Behav Brain Res 411:113380. doi: 10.1016/j.bbr.2021.113380

Objective: To characterize the effects of propofol on the profile of sleep–wake states and cortical electroencephalogram (EEG) power spectral density in rats following intraperitoneal injection.

Summary: The high dose of propofol produced high-quality sleep by increasing SWS2, whereas the medium dose produced fragmented and low-quality sleep by disrupting the continuity of wakefulness.

Usage: Bilateral injection of Orexin-SAP (92 and 184 ng/ml, 0.25 ml in the ventral tegmental area and 0.5 ml in the substantia nigra) of rats induced insomnia, as well as hyperactivity and stereotypic movements

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

See Also:

• Gerashchenko D et al. Insomnia following hypocretin2-saporin lesions of the substantia nigra. Neuroscience 137(1):29-36, 2006.

Whalley K (2021) Sneezing pathway revealed. Nat Rev Neurosci 22(8):455. doi: 10.1038/s41583-021-00491-3

See: Li F et al. Sneezing reflex is mediated by a peptidergic pathway from nose to brainstem. Cell 184(14):3762-3773.e10, 2021.

Related Products: NMB-SAP (Cat. #IT-70)

de Almeida AS, Bernardes LB, Trevisan G (2021) TRP channels in cancer pain. Eur J Pharmacol 904:174185. doi: 10.1016/j.ejphar.2021.174185 PMID: 34015320

Objective: To describe the role of TRP vanilloid 1 (TRPV1) and TRP ankyrin 1 (TRPA1) involved in cancer pain mechanisms.

Summary: Several studies have revealed that the administration of TRPV1 or TRPA1 agonists/antagonists and TRPV1 or TRPA1 knockdown reduced sensitivity to nociception in cancer pain models. Thus, TRP channels are potential targets for managing cancer-related pain syndromes.

Usage: Ablation of IB4 (+) neurons.

Related Products: IB4-SAP (Cat. #IT-10)

See Also:

• Ye Y et al. IB4(+) and TRPV1(+) sensory neurons mediate pain but not proliferation in a mouse model of squamous cell carcinoma. Behav Brain Funct 10(1):5, 2014.

Cano G, Hernan SL, Sved AF (2021) Centrally projecting edinger-westphal nucleus in the control of sympathetic outflow and energy homeostasis. Brain Sci 11(8):1005. doi: 10.3390/brainsci11081005

Objective: To test the hypothesis that Edinger-Westphal nucleus (EWcp) integrates multimodal signals (stress, thermal, metabolic, endocrine, etc.) and modulates the sympathetic output simultaneously to multiple effector organs to maintain energy homeostasis under different conditions that require adjustments of energy demands.

Summary: Besides its role in feeding/metabolic control and addiction, EWcp is involved in several important functions that are ultimately related to different aspects of stress responses, as well as stress coping and adaptation.

See: Xu L et al. Peptidergic Edinger-Westphal neurons and the energy-dependent stress response. Gen Comp Endocrinol 177(3):296-304, 2012.

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

McMahon D, O’Reilly MA, Hynynen K (2021) Therapeutic agent delivery across the blood-brain barrier using focused ultrasound. Annu Rev Biomed Eng 23:89-113. doi: 10.1146/annurev-bioeng-062117-121238 PMID: 33752471

Summary: Review of the use of focused ultrasound, in combination with circulating microbubbles, can be used to transiently and noninvasively increase cerebrovascular permeability with a high level of spatial precision. For minutes to hours following sonication, drugs can be administered systemically to extravasate in the targeted brain regions and exert a therapeutic effect, after which permeability returns to baseline levels.

Usage: Shin et al. reported improved spatial memory following FUS+MB exposure in a rat model of cholinergic neuron degeneration. 192-IgG-SAP was injected bilaterally into the lateral ventricle (4  μl at a concentration of 0.63  μg/μl at a rate of 1 μl/min).

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

See Also:

• Shin J et al. Focused ultrasound-induced blood-brain barrier opening improves adult hippocampal neurogenesis and cognitive function in a cholinergic degeneration dementia rat model. Alzheimers Res Ther 11(1):110, 2019.

Takeuchi Y, Nagy AJ, Barcsai L, Li Q, Ohsawa M, Mizuseki K, Berényi A (2021) The medial septum as a potential target for treating brain disorders associated with oscillopathies. Front Neural Circuits 15:701080. doi: 10.3389/fncir.2021.701080

Summary: The medial septum (MS) may be a potential target for treating neurological and psychiatric disorders with abnormal oscillations (oscillopathies) to restore healthy patterns or erase undesired ones. The time-targeted strategy for the MS stimulation may provide an effective way of treating multiple disorders.

Usage: 192-IgG-SAP. The MS cholinergic neurons along with theta oscillations are known to be essential for memory because selective lesion of the cholinergic neurons resulted in spatial memory impairments (150 ng; Easton et al., 2011) (5.04 μg icv; Jeong et al., 2014). Orexin-SAP. The enhanced gamma oscillations and altered PPI and auditory gating created by psychoactive drugs in rats were mediated by GABAergic neurons in the MS because they were abolished by ablation of these neurons by Orexin-SAP (140 ng total bilateral; Ma et al., 2012). mu p75-SAP. Anxious environment-induced type 2 theta oscillation and associated anxiety were shown to be dependent on the MS cholinergic neurons because lesion of MS cholinergic neurons reduced them (0.65 or 1.3 µg, bilateral; Nag et al., 2009).

Related Products: 192-IgG-SAP (Cat. #IT-01), mu p75-SAP (Cat. #IT-16), Orexin-B-SAP (Cat. #IT-20)

See Also:

• Easton A et al. Medial septal cholinergic neurons are necessary for context-place memory but not episodic-like memory. Hippocampus 21(9):1021-1027, 2011.
• Jeong D et al. Improvements in memory after medial septum stimulation are associated with changes in hippocampal cholinergic activity and neurogenesis. Biomed Res Int 2014:568587, 2014.
• Ma J et al. Septohippocampal GABAergic neurons mediate the altered behaviors induced by n-methyl-D-aspartate receptor antagonists. Hippocampus 22(12):2208-2218, 2012.
• Nag N et al. Efficacy of a murine-p75-saporin immunotoxin for selective lesions of basal forebrain cholinergic neurons in mice. Neurosci Lett 452:247-251, 2009.

Li F, Jiang H, Shen X, Yang W, Guo C, Wang Z, Xiao M, Cui L, Luo W, Kim BS, Chen Z, Huang AJW, Liu Q (2021) Sneezing reflex is mediated by a peptidergic pathway from nose to brainstem. Cell 184(14):3762-3773.e10. doi: 10.1016/j.cell.2021.05.017

Objective: To test the hypothesis that a neuronal population postsynaptic to nasal sensory neurons mediates sneezing.

Summary: Chemical activation of neuromedin B (NMB)-sensitive neurons elicits action potentials in caudal ventral respiratory group (cVRG) neurons and leads to sneezing behavior. This study delineates a peptidergic pathway mediating sneezing, providing molecular insights into the sneezing reflex arc.

Usage: Microinjection of NMB-saporin into the sneeze-evoking region abolished the sneezing responses to capsaicin and histamine.

Related Products: NMB-SAP (Cat. #IT-70)

Li Y, Bao Y, Zheng H, Qin Y, Hua B (2021) Can Src protein tyrosine kinase inhibitors be combined with opioid analgesics? Src and opioid-induced tolerance, hyperalgesia and addiction. Biomed Pharmacother 139:111653. doi: 10.1016/j.biopha.2021.111653

Summary: In this review the authors discuss the important role Src protein tyrosine kinase plays in the adverse consequences of clinical application of opioids

Usage: Intrathecal injection of Mac-1-SAP depletes microglial cells in the spinal dorsal horn and alleviates the loss of anti-nociception of morphine and prevents the decrease in morphine potency. This demonstrates that spinal microglial cells are necessary for morphine tolerance (15 µg; Leduc-Pessah et al., 2017).

See: Leduc-Pessah H et al. Site-Specific Regulation of P2X7 Receptor Function in Microglia Gates Morphine Analgesic Tolerance. J Neurosci 37:10154-10172, 2017.

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