targeted-toxins

Díaz HS, Andrade DC, Toledo C, Pereyra KV, Schwarz KG, Díaz-Jara E, Lucero C, Arce-Álvarez A, Schultz HD, Silva JN, Takakura AC, Moreira TS, Marcus NJ, Del Rio R (2020) Episodic stimulation of central chemoreceptor neurons elicits disordered breathing and autonomic dysfunction in volume overload heart failure. Am J Physiol Lung Cell Mol Physiol 318(1):L27-L40. doi: 10.1152/ajplung.00007.2019

Objective: To determine the role of the central chemoreflex in the development of respiratory and autonomic dysfunction in volume overload heart failure (HF).

Summary: Episodic hypercapnic stimulation triggers ventilatory plasticity and elicits cardiorespiratory abnormalities in HF that are largely dependent on retrotrapezoid nucleus (RTN) chemoreceptor neurons.

Usage: Bilateral injections of SSP-SAP, 0.6 ng/30 nL, into the RTN were administered to destroy chemoreceptor neurons.

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

Shin J, Kong C, Lee J, Choi BY, Sim J, Koh CS, Park M, Na YC, Suh SW, Chang WS, Chang JW (2019) 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. doi: 10.1186/s13195-019-0569-x

Objective: To investigate the decrease of adult hippocampal neurogenesis (AHN) in Alzheimer’s disease (AD).

Summary: This work studied the effect of FUS on AHN in a cholinergic degeneration rat model of dementia.

Usage: 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)

Kelly SC, McKay EC, Beck JS, Collier TJ, Dorrance AM, Counts SE (2019) Locus coeruleus degeneration induces forebrain vascular pathology in a transgenic rat model of alzheimer’s disease. J Alzheimers Dis 70(2):371-388. doi: 10.3233/JAD-190090 PMID: 31177220

Objective: To understand the extent to which locus coeruleus projection system degeneration influences vascular pathology.

Summary: Noradrenergic locus coeruleus (LC) neuron loss is a significant feature of mild cognitive impairment and Alzheimer’s disease (AD). The authors stereotactically lesioned LC projection neurons innervating the prefrontal cortex of six-month-old Tg344–19 AD rats using DBH-SAP, or an untargeted control IgG-SAP. DBH-sap-lesioned animals performed significantly worse than IgG-sap animals on the Barnes maze task in measures of both spatial and working memory. DBH-sap-lesioned rats also displayed increased amyloid and inflammation pathology compared to IgG-sap controls. Results indicate that LC projection system degeneration is a nexus lesion that compromises both vascular and neuronal function in cognitive brain areas during the prodromal stages of AD.

Usage: Anti-DBH-SAP (IT-03) or control Mouse IgG-sap (IT-18) were administered to the PFC bilaterally ( 2.5 μg/injection).

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

Rizvanovic H, Pinheiro AD, Kim K, Thomas J (2019) Chlorotoxin conjugated with saporin reduces viability of ML-1 thyroid cancer cells in vitro. bioRxiv 885483. doi: 10.1101/2019.12.20.885483

Objective: To determine whether Chlorotoxin-conjugated Saporin (CTX-SAP) would inhibit the growth of aggressive thyroid cancer cell lines expressing MMP-2.

Summary: This in vitro study demonstrated the efficacy of a CTX-SAP conjugate in reducing the viability of ML-1 thyroid cancer cells in a dose dependent manner.

Usage: There was a statistically significant reduction in cell viability with increasing concentrations of the CTX-SAP conjugate (biotinylated Chlorotoxin mixed with Streptavidin-ZAP). The cell viability of ML-1 cells was decreased by 49.77% with the treatment of 600 nM of CTX-SAP (F=44.24). Unconjugated Chlorotoxin or Saporin had no significant effect on cell viability a using similar assay.

Related Products: Streptavidin-ZAP (Cat. #IT-27), Saporin (Cat. #PR-01), Chlorotoxin-SAP (Cat. #IT-86)

Souza GMPR, Stornetta RL, Stornetta DS, Abbott SBG, Guyenet PG (2019) Contribution of the retrotrapezoid nucleus and carotid bodies to hypercapnia- and hypoxia-induced arousal from sleep. J Neurosci 39(49):9725-9737. doi: 10.1523/JNEUROSCI.1268-19.2019

Objective: To examine the contribution of two lower brainstem nuclei that could be implicated in CO2 and hypoxia-induced arousal.

Summary: RTN, a brainstem nucleus that mediates the effect of brain acidification on breathing, also contributes to arousal elicited by CO2 but not hypoxia.

Usage: To ablate the retrotrapezoid nucleus (RTN), SSP-SAP was administered (2.4 ng) through bilateral injections via a dorsal craniotomy.

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

Thorsdottir D, Cruickshank NC, Einwag Z, Hennig GW, Erdos B (2019) BDNF downregulates β-adrenergic receptor-mediated hypotensive mechanisms in the paraventricular nucleus of the hypothalamus. Am J Physiol Heart Circ Physiol 317(6):H1258-H1271. doi: 10.1152/ajpheart.00478.2019

Objective: To determine whether BDNF increases blood pressure in part by diminishing inhibitory hypotensive input from nucleus of the solitary tract (NTS) catecholaminergic neurons projecting to the PVN.

Summary: BDNF, a key hypothalamic regulator of blood pressure, disrupts catecholaminergic signaling between the NTS and the PVN by reducing the responsiveness of PVN neurons to inhibitory hypotensive β-adrenergic input from the NTS.

Usage: Bilateral NTS injections of sterile PBS (for control) or Anti-DBH-SAP (22 ng).

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

Goodman RL, He W, Lopez JA, Bedenbaugh MN, McCosh RB, Bowdridge EC, Coolen LM, Lehman MN, Hileman SM (2019) Evidence that the LH surge in ewes involves both neurokinin B–dependent and –independent actions of kisspeptin. Endocrinology 160(12):2990-3000. doi: 10.1210/en.2019-00597

Objective: To determine if NKB is involved in the RCh of the ewe in the LH surge.

Summary: NKB signaling in the RCh increases kisspeptin levels critical for the full amplitude of the LH surge in the ewe, but kisspeptin release occurs independently of retrochiamatic area (RCh) input at the onset of the surge to initiate GnRH secretion.

Usage: Bilaterial injections in the RCh of either NK3-SAP or Blank-SAP.

Related Products: NKB-SAP (Cat. #IT-63), Blank-SAP (Cat. #IT-21)

Toledo C, Andrade DC, Díaz HS, Pereyra KV, Schwarz KG, Díaz-Jara E, Oliveira LM, Takakura AC, Moreira TS, Schultz HD, Marcus NJ, Del Rio R (2019) Rostral ventrolateral medullary catecholaminergic neurones mediate irregular breathing pattern in volume overload heart failure rats. J Physiol 597(24):5799-5820. doi: 10.1113/JP278845

Objective: To investigate the potential contribution of RVLM‐C1 neurons to irregular breathing.

Summary: Findings suggest that RVLM‐C1 neurons play a pivotal role in breathing irregularities in volume overload HF, and mediate the sympathetic responses induced by acute central chemoreflex activation.

Usage: Anti-DBH-SAP was used to selectively lesion RVLM‐C1 neurons. Reduction (∼65%) of RVLM‐C1 neurons resulted in attenuation of irregular breathing, decreased apnea‐hypopnea incidence and improved cardiac autonomic control.

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

Díaz HS, Andrade DC, Toledo C, Lucero C, Arce-Álvarez A, Del Rio R (2019) Episodic stimulation of central chemoreflex elicits long-term breathing disorders and autonomic imbalance in heart failure rats. Eur Respir J 54(suppl 63):OA4936. doi: 10.1183/13993003.congress-2019.OA4936

Objective: To determine the role of CC in the development of cardiorespiratory dysfunction in a HF model.

Summary: Rats were exposed to pisodic hypercapnic stimulation (EHS) The effects of EHS in rats with heart failure were attenuated by SSP-SAP treatment.

Usage: Selective destruction of chemoreceptor neurons within the retrotapezoid nucleus (RTN) was performed via SSP-SAP injections (0.6 ng/30 nL).

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

Ueda H (2019) Systems pathology of neuropathic pain and fibromyalgia. Biol Pharm Bull 42(11):1773-1782. doi: 10.1248/bpb.b19-00535

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