targeted-toxins

Kaushal R, Taylor B, Jamal A, Zhang L, Ma F, Donahue R, Westlund K (2016) GABA-A receptor activity in the noradrenergic locus coeruleus drives trigeminal neuropathic pain in the rat; contribution of NAα1 receptors in the medial prefrontal cortex. Neuroscience 334:148-159. doi: 10.1016/j.neuroscience.2016.08.005

Summary: The goal of this study was to investigate the role of the locus coeruleus (LC) in a rat orofacial pain model of trigeminal neuropathy induced by chronic constrictive injury of the infraorbital nerve (CCI-ION). Mechanical thresholds to von Frey filaments were tested on whisker pads to evaluate neuropathic pain behavior; pain was indicated by development of mechanical hypersensitivity. Noradrenergic (NA) neurons were lesioned with 5-mcg injections of Anti-DBH-SAP (Cat. #IT-03) into the left lateral ventricle. Mouse-IgG-SAP (Cat. #IT-18) was used as a control. After ablation of NA neurons there was a notable increase in the mechanical threshold compared to control animals. They also targeted coeruleotrigeminal NA neurons by injecting Anti-DBH-SAP into the trigeminal brainstem nuclei bilaterally in one animal and saw similar results. Injecting a GABAA receptor antagonist into the LC after injury had an inhibitory effect on nerve injury induced hypersensitivity. Injection of a NAα1 receptor antagonist, but not a NAα2 receptor antagonist, into the medial prefrontal cortex (mPFC) alleviates mechanical hypersensitivity. They conclude that GABAA-mediated activation of NA neurons during CCI-ION can facilitate hypersensitivity through NAα1 receptors in the mPFC, and that the LC is a chronic pain generator.

Related Products: Anti-DBH-SAP (Cat. #IT-03), Mouse IgG-SAP (Cat. #IT-18)

Nam H, Kerman I (2016) A2 noradrenergic neurons regulate forced swim test immobility. Physiol Behav 165:339-349. doi: 10.1016/j.physbeh.2016.08.020

Summary: Wistar-Kyoto rats are often used as a model of depression, and exhibit high levels of immobility when subjected to a forced swim test (FST). Researchers discovered relative hyperactivation in the locus coeruleus of WKY rats compared to the genetically related Wistar rats when exposed to one- and two-day FSTs. Lesser activation of A2 noradrenergic cell group was seen by diminished levels of FOS after both days of the FST. A2 noradrenergic neurons of Winstar rats were lesioned by injecting 2.2 ug of Anti-DBH-SAP (Cat. #IT-03) into the nucleus tractus solitaris (NTS). Lesioned rats exhibited increased FST immobility on both days of the test, similar to natural WKY behavior in the same test. These data indicate that the A2 noradrenergic cell group regulates FST behavior and that its hypoactivation may contribute to the unique behavioral phenotype of WKY rats.

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

Paban V, Valable S, Baril N, Gilbert V, Chambon C, & Alescio-Lautier B (2016) Neuronal and glial changes in rat hippocampal formation after cholinergic deafferentation. J Biomol Res Ther 5(3):1000147. doi: 10.4172/2167-7956.1000147

Summary: The effects of cholinergic insult were studied in the hippocampal formation of cholinergic lesioned rats at metabolic and cellular levels by in vivo nuclear magnetic resonance spectrometry and immuno-histochemical approaches.

Usage: Cholinergic deafferentation was induced by injection of the cholinergic immunotoxin 192-IgG-SAP into the medial septum (37.5 ng/side).

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

Kumar JR, Rajkumar R, Lee LC, Dawe GS (2016) Featured Article: Targeted lesioning reveals role of nucleus incertus in the anxiogenic effect of buspirone. Targeting Trends 17(4)

Related Products: CRF-SAP (Cat. #IT-13)

Read the featured article in Targeting Trends.

See Also:

• Kumar J et al. Nucleus incertus contributes to an anxiogenic effect of buspirone in rats: Involvement of 5-HT1A receptors. Neuropharmacology 110:1-14, 2016.

Cai Y, Chew C, Muñoz F, Sengelaub D (2017) Neuroprotective effects of testosterone metabolites and dependency on receptor action on the morphology of somatic motoneurons following the death of neighboring motoneurons. Dev Neurobiol 77:691-707.. doi: 10.1002/dneu.22445

Summary: In this study the authors examined whether the protective effects of testosterone could be mediated via its androgenic or estrogenic metabolites and if these neuroprotective effects were mediated through steroid hormone receptors. Analysis was done using receptor antagonists to attempt to prevent the neuroprotective effects of hormones after partial motoneuron depletion. These motoneurons were selectively killed by intramuscular injection of CTB-SAP (2 ul, 0.1%) (Cat. #IT-14). Compared with intact normal animals, partial motoneuron depletion resulted in decreased dendritic length in remaining quadriceps motoneurons. Dendritic atrophy was attenuated with both dihydrotestosterone and estradiol treatment to a degree similar to that seen with testosterone and attenuation of atrophy was prevented by receptor blockade. Together, the results suggest that neuroprotective effects on motoneurons can be mediated by either androgenic or estrogenic hormones and require action via steroid hormone receptors, further supporting a role for hormones as neurotherapeutic agents in the injured nervous system.

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

Young J (2016) Hunger, thirst, sex, and sleep: How the brain controls our passions. Rowman & Littlefield Publishers.

Summary: The author reviews what has been learned about feeding, “Other clever techniques have confirmed that leptin specifically acts upon NPY-containing neurons to depress feeding. One technique is to infuse the hypothalamus with a form of NPY that is linked to a poisonous molecule called saporin. Neurons that normally contain NPY usually release it into their surroundings and then specifically take it back up into the cell so that it is not wasted. When NPY-containing neurons are tricked into taking up NPY linked to saporin, they die but leave other adjacent neurons completely unaffected. Rats treated in this way become completely insensitive to the feeding-restraining effects of leptin because they lack NPY-containing neurons in the arcuate nucleus.”

Related Products: Blank-SAP (Cat. #IT-21), NPY-SAP (Cat. #IT-28)

See Also:

• Bugarith K et al. Basomedial hypothalamic injections of neuropeptide Y conjugated to saporin selectively disrupt hypothalamic controls of food intake. Endocrinology 146(3):1179-1191, 2005.

Silva T, Takakura A, Moreira T (2016) Acute hypoxia activates hypothalamic paraventricular nucleus-projecting catecholaminergic neurons in the C1 region. Exp Neurol 285:1-11. doi: 10.1016/j.expneurol.2016.08.016

Summary: Catecholaminergic C1 cells reside in the rostral and intermediate portions of the ventrolateral medulla (RVLM) and can be activated by hypoxia. These neurons regulate the hypothalamic pituitary axis via direct projections to the hypothalamic paraventricular nucleus (PVH) and regulate the autonomic nervous system via projections to sympathetic and parasympathetic preganglionic neurons. The present results suggest that catecholaminergic C1-PVH projection is hypoxia-sensitive and the pathway between these two important brain areas can be one more piece in the complex puzzle of neural control of autonomic regulation during hypoxia. Male Wistar rats were injected with the targeted toxin Anti-DβH-SAP (Cat. #IT-03), 21 ng/100 nl, or saline, unilaterally into the PVH using the following coordinates: 1.2 mm caudal to bregma, 0.4 mm lateral to the midline and 7.8 mm below the dura mater. The author’s work adds a piece in the complex puzzle of the physiological role of the C1 cells by showing that this catecholaminergic group of cells must be activated only in emergency situations such as acute hypoxia, producing autonomic, metabolic, and neuroendocrine responses designed to help the organism survive major acute physical stresses.

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

Coradazzi M, Gulino R, Fieramosca F, Falzacappa L, Riggi M, Leanza G (2016) Selective noradrenaline depletion impairs working memory and hippocampal neurogenesis. Neurobiol Aging 48:93-102. doi: 10.1016/j.neurobiolaging.2016.08.012

Summary: Neuronal loss in the locus coeruleus (LC) of Alzheimer’s patients is well known, but the contribution of LC-derived noradrenergic afferents to learning and memory function is unknown. To model noradrenergic neuron degeneration in the LC, rats were bilaterally injected directly into the LC with 0.2 ug of Anti-DBH-SAP (Cat. #IT-03). Lesioned and sham-lesioned animals were tested behaviorally and exhibited robust working memory deficits but lesioning did not affect reference memory. They concluded that ascending noradrenergic afferents might be involved in more complex aspects of working memory, possibly via newly generated progenitors in the hippocampus.

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

Kucinski A, de Jong IEM, Sarter M (2017) Reducing falls in Parkinson’s disease: interactions between donepezil and the 5‐HT6 receptor antagonist idalopirdine on falls in a rat model of impaired cognitive control of complex movements. Eur J Neurosci 45:217-231.. doi: 10.1111/ejn.13354

Objective: To assess the effects of treatment on MCMCT performance and attention in DL rats. The combined treatment of the acetylcholinesterase inhibitor donepezil and the 5-HT6 receptor antagonist idalopirdine (Lu AE58054) was use because it has been reported to exhibit synergistic pro-cholinergic activity in rats and improved cognition in patients with moderate Alzheimer’s disease.

Summary: This treatment may reduce fall propensity in patients.

Usage: 192-IgG-SAP aCSF infused bilaterally (120 ng/uL; 0.5 uL/hemisphere).

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

Araldi D, Ferrari L, Levine J (2016) Gi-protein-coupled 5-HT1B/D receptor agonist sumatriptan induces type I hyperalgesic priming. Pain 157:1773-1782. doi: 10.1097/j.pain.0000000000000581

Summary: The present study explored the possibility that, like MOR and A1-adenosine receptor agonists, triptans would also induce type II hyperalgesic priming. In addition, they explored the 5-HT receptor subtypes at which triptans act (5-HT1B, 5-HT1D and 5-HT7) to induce priming. They report that while sumatriptan, a prototypical 5-HT1B/D receptor agonist induces hyperalgesic priming, this priming meets the criteria for type I rather than type II priming. Isolectin B4 (IB4)-saporin (Cat. #IT-10), was diluted in saline, and a dose of 3.2 μg, in a volume of 20 μL was administered intrathecally to rats. The neurotoxin [Sar9,Met(O2) 11]-substance P-saporin (SSP-Saporin, Cat. #IT-11) was diluted in saline, and a dose of 100 ng, in a volume of 20 μL was administered intrathecally. In a model of pain chronification, sumatriptan induces both mechanical hyperalgesia at the site of injection and type I hyperalgesic priming, in nociceptors innervating the cutaneous injection site.

Related Products: IB4-SAP (Cat. #IT-10), SSP-SAP (Cat. #IT-11)