2021 Targeting Trends Review

Liu X, Wang Y, Tao T, Zeng L, Wang D, Wen Y, Li Y, Zhao Z, Tao A (2021) GRPR/extracellular signal-regulated kinase and NPRA/extracellular signal-regulated kinase signaling pathways play a critical role in spinal transmission of chronic itch. J Invest Dermatol 141(4):863-873. doi: 10.1016/j.jid.2020.09.008

Summary: This study investigates whether there are certain key signaling molecules downstream of the recently identified peptides mediating itch in the spinal cord. Bombesin-SAP completely abolished extracellular signal-regulated kinase (ERK) activation. ERK was the most highly activated by their agonists BNP (Nppb, brain-derived natriuretic peptide) and octreotide. Nppb-SAP only partially reduced pERK in cervical spinal cord.

Related Products: Bombesin-SAP (Cat. #IT-40), Nppb-SAP (Cat. #IT-69)

Chen P, Pan M, Lin QS, Lin XZ, Lin Z (2021) CSF-CN contributes to cancer-induced bone pain via the MKP-1-mediated MAPK pathway. Biochem Biophys Res Commun 547:36-43. doi: 10.1016/j.bbrc.2021.02.010

Summary: Cerebrospinal fluid-contacting nucleus (CSF–CN) has been reported to be involved in the development of neuropathic pain and inflammatory pain. This study aimed to see whether it also has a role in cancer-induced bone pain (CIBP). Targeted ablation of CSF-CN dramatically aggravated pain sensitivity.

Usage: Injection via icv of CTB-SAP was performed to “knockout” the CSF-CN.

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

Xu Q, Wang DR, Dong H, Chen L, Lu J, Lazarus M, Cherasse Y, Chen GH, Qu WM, Huang ZL (2021) Medial parabrachial nucleus is essential in controlling wakefulness in rats. Front Neurosci 15:645877. doi: 10.3389/fnins.2021.645877

Summary: Lesions of the LC with 192-IgG-SAP have no significant effect on wakefulness in rats (Blanco-Centurion et al.). Only the Orexin-SAP lesion involved in the MPB region resulted in the dramatic decrease of wakefulness in rats (Fuller et al.).

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

See Also:

• Blanco-Centurion C et al. Effects of saporin-induced lesions of three arousal populations on daily levels of sleep and wake. J Neurosci 27:14041-14048, 2007.
• Fuller P et al. Reassessment of the structural basis of the ascending arousal system. J Comp Neurol 519(5):933-956, 2011.

Dinh HT, Nishimaru H, Le QV, Matsumoto J, Setogawa T, Maior RS, Tomaz C, Ono T, Nishijo H (2021) Preferential neuronal responses to snakes in the monkey medial prefrontal cortex support an evolutionary origin for ophidiophobia. Front Behav Neurosci 15:653250. doi: 10.3389/fnbeh.2021.653250

Summary: Ophidiophobia (snake phobia) is one of the most common specific phobias. Noninvasive imaging studies of patients with specific phobia reported that the medial prefrontal cortex (mPFC), especially the rostral part of the anterior cingulate cortex (rACC), and amygdala are activated during the presentation of phobogenic stimuli. Attentional bias to specific animals promotes anxiety and phobia. The mPFC is reported to be involved in attentional allocation to various salient visual stimuli. The findings suggest that the rACC focuses attention on snakes, and promotes aversive conditioning to snakes, which may lead to anxiety and ophidiophobia.

Usage: Prior work has demonstrated that lesions of the cortical cholinergic system of the basal forebrain impair performance in attentional tasks. 192-IgG-SAP (50 or 100 ng) was infused into the PFC of rats.

See: Dalley JW et al. Cortical cholinergic function and deficits in visual attentional performance in rats following 192 IgG-Saporin-induced lesions of the medial prefrontal cortex. Cereb Cortex 14(8):922-932, 2004.

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

Li T, Zhao J, Xie W, Yuan W, Guo J, Pang S, Gan WB, Gómez-Nicola D, Zhang S (2021) Specific depletion of resident microglia in the early stage of stroke reduces cerebral ischemic damage. J Neuroinflammation 18(1):81. doi: 10.1186/s12974-021-02127-w

Summary: The role of activated microglia during the development of ischemia remains controversial. The authors investigate the function of reactive microglia in the early stage of ischemic stroke. The results showed that specific depletion of microglia resulted in a significant decrease in ischemic infarct volume and improved performance in motor ability 3 days after stroke.

Usage: Mac-1-SAP is used to specifically eliminate microglia. Hippocampal slices from mouse were incubated with 13-nM Mac-1-SAP for 3 to 7 days.

See: Montero M et al. Immunotoxic depletion of microglia in mouse hippocampal slice cultures enhances ischemia-like neurodegeneration. Brain Res 1291:140-152, 2009.

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

Sun S, Ding Z, Yang X, Zhao X, Zhao M, Gao L, Chen Q, Xie S, Liu A, Yin S, Xu Z, Lu X (2021) Nanobody: a small antibody with big implications for tumor therapeutic strategy. Int J Nanomedicine 16:2337-2356. doi: 10.2147/IJN.S297631

Summary: This Journal Club commentary focuses on the publication by Kalinchuk et al.

Usage: The author refers to work with 192-IgG-SAP published by Blanco-Centurion et al. This group investigated whether basal forebrain cholinergic neurons are involved in adenosine regulation of sleep. 6 µg of 192-IgG-SAP was administered to the lateral ventricle of rats.

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

See Also:

• Blanco-Centurion C et al. Adenosine and sleep homeostasis in the basal forebrain. J Neurosci 26(31):8092-8100, 2006.
• Kalinchuk AV et al. The role of cholinergic basal forebrain neurons in adenosine-mediated homeostatic control of sleep: lessons from 192 IgG-saporin lesions. Neuroscience 157:238-253, 2008.

Eu WZ, Chen YJ, Chen WT, Wu KY, Tsai CY, Cheng SJ, Carter RN, Huang GJ (2021) The effect of nerve growth factor on supporting spatial memory depends upon hippocampal cholinergic innervation. Transl Psychiatry 11(1):162. doi: 10.1038/s41398-021-01280-3

Objective: To determine whether the supportive effect of NGF on learning and memory is specifically dependent upon intact hippocampal cholinergic innervation.

Summary: The results demonstrate that the hippocampal cholinergic system is required for maintaining spatial memory function, without having an impact on anxiety.

Usage: Twelve-week-old male C57BL/6Narl mice were used for hippocampal cholinergic denervation. Mice received bilateral injections into the hippocampus; 0.2 μg of mu p75-SAP was administered per site.

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

Sato M, Saitoh I, Akasaka E, Inada E (2021) Development of a novel pipette tip-aided cell cloning method for the effective isolation of genome-edited porcine cell. OBM Genetics 5(1):16. doi: 10.21926/obm.genet.2101126

Summary: Isolation of clonal cells from a single colony is an essential step in the process of obtaining pure populations of stably-transfected clones after gene transfer and the subsequent drug selection. In the present study, a novel, simple, and non-invasive technique for the isolation of cells from single colonies using a disposable pipette tip was developed.

Usage: A toxin-based, drug-free selection system involving IB4-SAP was employed in the present study.

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

Geraghty T, Winter DR, Miller RJ, Miller RE, Malfait AM (2021) Neuroimmune interactions and osteoarthritis pain: focus on macrophages. Pain Rep 6(1):e892. doi: 10.1097/PR9.0000000000000892

Summary: The contribution of macrophages to osteoarthritis (OA) joint damage has garnered much attention in recent years. The authors discuss how macrophages participate in the initiation and maintenance of pain in OA and provide a review of preclinical models of OA.

Usage: Using the rat monoiodoacetate-induced (MIA) model of advanced knee OA, increased microglia were observed in the ipsilateral and contralateral dorsal horn by day 7; specific ablation of spinal microglia through intrathecal injections of Mac-1-SAP (15 mcg per intrathecal injection on days 0, 1, and 2), attenuated mechanical allodynia by days 5 and 7 after MIA.

See: Mousseau M et al. Microglial pannexin-1 channel activation is a spinal determinant of joint pain. Sci Adv 4:1-12, 2018.

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

Andriessen AS, Donnelly CR, Ji RR (2021) Reciprocal interactions between osteoclasts and nociceptive sensory neurons in bone cancer pain. Pain Rep 6(1):e867. doi: 10.1097/PR9.0000000000000867

Summary: Current pharmacotherapies available for bone cancer pain are insufficient to provide safe and efficacious pain relief. The authors discuss the mechanisms used by cancer cells within the bone tumor microenvironment (TME) to drive bone cancer pain.

Usage: Microglial ablation using Mac-1-SAP (15 μg in 8.8 μl i.t.) and Saporin control (Cat. #PR-01, 8.8 μg in 8.8 μl), is sufficient to attenuate nerve injury-induced pain in male, but not female mice.

See: Sorge R et al. Different immune cells mediate mechanical pain hypersensitivity in male and female mice. Nat Neurosci 18:1081-1083, 2015.

Related Products: Mac-1-SAP mouse/human (Cat. #IT-06), Saporin (Cat. #PR-01)