targeted-toxins

Sharma R, Sahota P, Thakkar M (2017) Lesion of the basal forebrain cholinergic neurons attenuates sleepiness and adenosine after alcohol consumption. J Neurochem 142:710-720.. doi: 10.1111/jnc.14054

Summary: This project examined the sleep-promoting effect of alcohol and which neurons in the brain are involved in the process. 192-IgG-SAP (Cat. #IT-01; 0.3 µg/500 nL/side) was administered through bilateral basal forebrain infusions in rats. Based on the results, the authors suggest that alcohol promotes sleep by increasing extracellular adenosine via its action on cholinergic neurons of the basal forebrain.

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

Fu C, Xue J, Wang R, Chen J, Ma L, Liu Y, Wang X, Guo F, Zhang Y, Zhang X, Wang S (2017) Chemosensitive Phox2b-expressing neurons are crucial for hypercapnic ventilatory response in the nucleus tractus solitarius. J Physiol 595:4973-4989.. doi: 10.1113/JP274437

Objective: To investigate whether paired-like homeobox 2b  (Phox2b)-expressing NTS neurons are recruited in hypercapnic ventilatory response (HCVR)  and whether these neurons exhibit intrinsic chemosensitivity.

Summary: Respiratory deficits caused by injection of SSP-SAP into the NTS are attributable to proportional lesions of CO2/H+-sensitive Phox2b-expressing neurons.

Usage: Two protocols were applied for SSP-SAP injections. In immunostaining experiments, to determine how many Phox2b-containing cells were destroyed, a total volume of 100 nl of PBS containing 6 ng of SSP-SAP (3 ng in 50 nl; 2 injections) was injected into one side of the NTS and the contralateral NTS was used as a control (no injection).  For in vivo experiments, to determine whether loss of Phox2b cells led to impaired HCVR, bilateral injections with a total volume of 200 nl of PBS containing 6 ng (1.5 ng in 50 nl per injection; 2 injections per side) or 12 ng (3 ng in 50 nl per injection; two injections per side) of toxin into NTS.  Breathing was studied in conscious, freely moving mice treated with SSP-SAP and Blank-SAP.

Related Products: SSP-SAP (Cat. #IT-11), Blank-SAP (Cat. #IT-21)

Yaksh T, Fisher C, Hockman T, Wiese A (2017) Current and future issues in the development of spinal agents for the management of pain. Curr Neuropharmacol 15:232-259.. doi: 10.2174/1570159×14666160307145542

Summary: Although conscious pain experience is driven by signals mediated supraspinally, the more high intensity pain generated by strong stimuli, tissue injury, and nerve injury is encoded at the spinal dorsal horn level. The control of pain signals at the spinal dorsal horn level is a tempting target for targeted pain therapy. This review discusses the potential targets for pain therapeutics in the spinal dorsal horn, and some of the spinal agents used to modulate pain transmission through that location. The use of SSP-SAP (Cat. #IT-11) is mentioned as a neurokinin-1 targeted molecule that can block some pain transmission.

Related Products: SSP-SAP (Cat. #IT-11)

Taxini CL, Moreira TS, Takakura AC, Bicego KC, Gargaglioni LH, Zoccal DB (2017) Role of A5 noradrenergic neurons in the chemoreflex control of respiratory and sympathetic activities in unanesthetized conditions. Neuroscience 354:146-157.. doi: 10.1016/j.neuroscience.2017.04.033

Summary: The authors utilize Anti-DBH-SAP (Cat. #IT-03) to investigate the involvement of the A5 noradrenergic neurons to the basal and chemoreflex control of the sympathetic and respiratory activities in unanesthetized conditions.

Related Products: Anti-DBH-SAP (Cat. #IT-03)

Taylor BK, Westlund KN (2017) The noradrenergic locus coeruleus as a chronic pain generator. J Neurosci Res 95(6):1336-1346. doi: 10.1002/jnr.23956 PMID: 27685982

Objective: To evaluate whether noradrenergic neurons of the locus coeruleus contribute to the generation and maintenance of chronic neuropathic pain rather than serving solely a pain inhibitory role.

Summary: This review synthesizes evidence showing that noradrenergic signaling from the locus coeruleus can facilitate neuropathic pain following nerve injury, challenging the traditional view of the LC as purely analgesic. Collectively, lesion, pharmacological, and circuit-level studies support a time dependent shift from pain inhibition to pain facilitation mediated by noradrenergic pathways.

Usage: This review summarizes multiple studies that utilized Anti-DBH-SAP (IT-03) to selectively ablate central noradrenergic neurons via intracerebroventricular or region-specific injections, demonstrating reduced mechanical and cold hypersensitivity in rodent models of neuropathic pain.

Related Products: Anti-DBH-SAP (Cat. #IT-03)

Lee S, Cho W, Lee Y, Han J (2018) Impact of chronic stress on the spatial learning and GR-PKAc-NF-κB signaling in the hippocampus and cortex in rats following cholinergic depletion. Mol Neurobiol 55:3976-3989. doi: 10.1007/s12035-017-0620-5

Objective: Examine the effects of chronic stress on cognitive status and GR-PKAc-NF-κB signaling in rats with a loss of cholinergic input to the hippocampus and cortex.

Summary: The activation of NF-κB induced by cholinergic depletion appears to be aggravated by chronic stress, and this might explain the increased susceptibility of patients with Alzheimer’s disease to stress since activation of NF-κB is associated with stress.

Usage: Male Sprague-Dawley rats received injections of 192 IgG-SAP dissolved in sterile 0.01 M PBS) at a concentration of 0.25 μg/μl.

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

Havelin J, Imbert I, Sukhtankar D, Remeniuk B, Pelletier I, Gentry J, Okun A, Tiutan T, Porreca F, King T (2017) Mediation of movement-induced breakthrough cancer pain by IB4-binding nociceptors in rats. J Neurosci 37:5111-5122.. doi: 10.1523/JNEUROSCI.1212-16.2017

Objective: To define a novel preclinical measure of movement-induced breakthrough pain (BTP) that is observed in the presence of morphine controlling ongoing pain.

Summary: Novel compounds targeting IB4-binding nociceptors may improve pain management for cancer pain patients and other patient populations suffering from BTP that is inadequately treated by currently available medications.

Usage: To determine the effect of eliminating input from IB4-binding fibers, separate groups of rats received spinal administration of IB4-SAP or the control, Blank-SAP (3.2 mcg/20 mcl saline) followed by a 10 mcl flush of saline. Movement of an air bubble placed between drug solution and saline was used to monitor progress of the injection.

Related Products: IB4-SAP (Cat. #IT-10), Blank-SAP (Cat. #IT-21)

Craig TA, Brown SM, Nichols NL (2017) Adenosine 2A (A2A) receptor expression in rats with motor neuron death from intrapleural CTB-saporin injections. FASEB J 31(S1):873.14. Experimental Biology 2017 Meeting Abstracts. doi: 10.1096/fasebj.31.1_supplement.873.14

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

Nichols NL, Tanner M (2017) Phrenic long-term facilitation (pLTF) following acute intermittent hypoxia (AIH) is TrkB and PI3K/Akt dependent in rats with motor neuron death from intrapleural CTB-saporin injections. FASEB J 31(S1):1053.13. Experimental Biology 2017 Meeting Abstracts. doi: 10.1096/fasebj.31.1_supplement.1053.13

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

Jenrette T, Logue J, Horner KA (2017) Striatal patch compartment lesions reduce habitual behaviors. FASEB J 31(S1):1059.6. Experimental Biology 2017 Meeting Abstracts. doi: 10.1096/fasebj.31.1_supplement.1059.6

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