targeted-toxins

Keilhoz A, Pathak I, Smith CL, Osman KL, Smith L, Oti G, Golzy M, Mz L, Lever TE, Nichols NL (2024) Tongue exercise ameliorates structural and functional upper airway deficits in a rodent model of hypoglossal motor neuron loss. Front Neurol 15:1441529. doi: 10.3389/fneur.2024.1441529 PMID: 39296960

Objective: To investigate the effects of a strength endurance tongue exercise program on upper airway structure and function.

Summary: Results showed that sham exercise-treated CTB-SAP rats have evidence of upper airway restriction (i.e., reduced airflow) and structural changes present in the upper airway (i.e., airway compression) when compared to rats treated with CTB-SAP and exercise and control rats with/without tongue exercise, which were ameliorated with tongue exercise. Additionally, CTB-SAP treated, sham exercise rats have evidence of increased lipid expression in the tongue consistent with previously observed tongue hypertrophy when compared to CTB-SAP treated exercise rats or control rats with/without tongue exercise.

Usage: Intralingual injection of either unconjugated CTB+SAP (20 μg CTB+25 μg SAP) or conjugated CTB-SAP (25 μg of CTB conjugated to SAP).

Related Products: CTB-SAP (Cat. #IT-14), Recombinant Cholera Toxin B (Cat. #PR-14), Saporin (Cat. #PR-01)

Kostenko A, Prezzavento O, de Leo G, D’Arco D, Gulion R, Caccamo A, Leanza G (2024) Cognitive and histopathological alterations in rat models of early- and late-phase memory dysfunction: Effects of sigma-1 receptor activation. J Alzheimers Dis 101(3) doi: 10.3233/JAD-240618 PMID: 39240642

Objective: This study sought to assess the role of (±)-cyclopropane carboxylate (PPCC) on working memory deficits caused by noradrenergic depletion.

Summary: While (±)-PPCC alone at a dose of 1 mg/kg/day failed to affect working memory in lesioned animals, its association with the α2 adrenergic receptor agonist clonidine, completely blocked noradrenaline release, significantly improving rat performance. This effect, distinct from noradrenaline activity, is likely to result from a direct action of the (±)-PPCC compound onto sigma-1 receptors, as pre-treatment with the selective sigma-1 receptor antagonist BD-1047 reversed the improved working memory performance. Despite such clear functional effects, the treatment did not affect noradrenergic neuron survival or terminal fiber proliferation.

Usage: Bilateral intraventricular injections of anti-DBH-saporin (IT-03). Either 1.25μg or 2.5μg of the immunotoxin was dissolved in 7μl of sterile PBS and administered into each lateral ventricle (resulting in a total of 2.5μg or 5.0μg per rat in a 7 + 7μl volume of vehicle).

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

Runyon K, Bui T, Mazanek S, Hartle A, Marschalko K, Howe WM (2024) Distinct cholinergic circuits underlie discrete effects of reward on attention. Front Mol Neurosci. Front Mol Neurosci 17:1429316. doi: 10.3389/fnmol.2024.1429316 PMID: 39268248

Objective: Review the basic neuroanatomy of attention, reward, and cholinergic systems.

Summary: Authors examined specific contexts in which attention and reward computations interact. They proposed two discrete neural circuits whereby acetylcholine, released from cell groups located in different parts of the brain, mediates the impact of stimulus-reward associations as well as motivation on attentional control. Authors concluded by examining these circuits as a potential shared loci of dysfunction across diseases states associated with deficits in attention and reward.

Usage: Lesions of basal forebrain via ACh-immunotoxin 192-IgG-SAP (IT-01) impaired performance on a sustained attention task designed for rodents, selectively reducing the capacity of rats to report the presence of instructive cues, while having no effect on their ability to report the absence of these cues0

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

See Also:

• McGaughy J et al. Behavioral vigilance following infusions of 192 IgG-saporin into the basal forebrain: selectivity of the behavioral impairment and relation to cortical AChE-positive fiber density. Behav Neurosci 110:247-265, 1996.

Huo C, Lombardi F, Blanco-Centurion C, Shiromani PJ, Ivanov PC (2024) Role of the locus coeruleus arousal promoting neurons in maintaining brain criticality across the sleep-wake cycle. J Neurosci 44(35):e1939232024. doi: 10.1523/JNEUROSCI.1939-23.2024 PMID: 38951035

Objective: To investigate dynamics of θ- and δ-bursts during the sleep-wake cycle of rats with lesion in the wake-promoting locus coeruleus (LC).

Summary: The findings indicate that critical dynamics of θ- and δ-bursts arise from a balanced interplay of LC and ventrolateral preoptic nucleus (VLPO), which maintains brain tuning to criticality across the sleep-wake cycle.

Usage: To confirm the efficacy of anti-DBH-SAP (IT-03) to kill noradrenergic-LC neurons and their fibers. 192 IgG-SAP (IT-01) was selected as an additional control because like anti-DBH-SAP it is a conjugate of a monoclonal antibody and saporin. Bilateral microinjection of 192-IgG-SAP and Anti-DBH-SAP were used at a volume of 0.3μL at a rate of 0.1μL/5 min using a pressure injector

Related Products: 192-IgG-SAP (Cat. #IT-01), Anti-DBH-SAP (Cat. #IT-03)

Konofal E (2024) From past to future: 50 years of pharmacological interventions to treat narcolepsy. Pharmacol Biochem Behav 241:173804. doi: 10.1016/j.pbb.2024.173804 PMID: 38852786

Objective: This review article discusses the historical progression and transformative insights that have characterized the treatment of narcolepsy from its initial documentation to the present day.

Summary: The research continues to push the boundaries of what is known about this complex sleep disorder, the hope for treatments that can fundamentally alter the disease trajectory becomes increasingly tangible. This paradigm shift towards addressing the autoimmune, neuroinflammatory, and neurodegenerative aspects of narcolepsy promises to revolutionize patient care.

Usage: See also these references using Orexin-B-SAP (IT-20) to create a narcoleptic-like rat model via LH lesions.

See Also:

• Gerashchenko D et al. Hypocretin-2-saporin lesions of the lateral hypothalamus produce narcoleptic-like sleep behavior in the rat. J Neurosci 21(18):7273-7283, 2001.
• Gerashchenko K et al. Effects of lateral hypothalamic lesion with the neurotoxin hypocretin-2-saporin on sleep in Long-Evans rats. Neuroscience 116:223-235, 2003.

Guo SS, Gong Y, Zhang TT, Su XY, Wu YJ, Yan YX, Cao Y, Song XL, Xie JC, Wu D, Jiang Q, Li Y, Zhao X, Zhu MX, Xu TL, Liu MG (2024) A thalamic nucleus reuniens-lateral septum-lateral hypothalamus circuit for comorbid anxiety-like behaviors in chronic itch. Sci Adv 10(33):eadn6272. doi: 10.1126/sciadv.adn6272 PMID: 39150998

Objective: To investigate anxiety-like behaviors in mouse models of chronic itch and identify lateral septum (LS) GABAergic neurons as key mediators through thalamic and hypothalamic circuit interactions.

Summary: Chronic itch amplifies excitatory inputs from the thalamic nucleus reuniens to LS GABAergic neurons, promoting anxiety-like behaviors. Inhibiting the Re → LS circuit reduces anxiety related to chronic itch but not restraint stress, highlighting its specificity. LS GABAergic neurons suppress lateral hypothalamus activity to mediate chronic itch-induced anxiety, with Bombesin-SAP targeting spinal itch neurons to confirm this pathway’s role.

Usage: Mice were intrathecally injected with Bombesin-SAP (IT-40) (400 ng/5 μl). Blank-SAP (IT-21) (400 ng/5 μl) was administered similarly to a control.

Related Products: Bombesin-SAP (Cat. #IT-40), Blank-SAP (Cat. #IT-21)

Shanahan SL, Kunder N, Inaku C, Hagan NB, Gibbons G, Mathey-Andrews N, Anandappa G, Soares S, Pauken KE, Jacks T, Schenkel JM (2024) Longitudinal intravascular antibody labeling identified regulatory t cell recruitment as a therapeutic target in a mouse model of lung cancer. J Immunol ji2400268. doi: 10.4049/jimmunol.2400268 PMID: 39082930

Objective: To develop an intravascular antibody technique to label circulating mouse leukocytes before they migrate to tissues, providing unprecedented insight into the kinetics of recruitment.

Summary: Leukocyte trafficking depended on the integrins CD11a/CD49d, and CD11a/CD49d blockade led to significant tumor burden reduction in mice. Preventing circulating Treg recruitment through depletion or sequestration in lymph nodes was sufficient to decrease tumor burden, indicating that Treg migration was crucial for suppressing antitumor immunity.

Usage: To deplete circulating Tregs, mice were treated every other day with 20mg of Anti-CD25 SAP (IT-29) for 6 days.

Related Products: Anti-CD25-SAP mouse (Cat. #IT-29)

Islam S, Gleber-Netto FO, Mulcahy CF, Glaun MDE, Srivastava S, Hunt PJ, Williams MD, Barbon CE, Spiotto M, Zhao W, Adebayo A, Akhter S, Xie T, Debnath KC, Sathishkumar HN, Myers B, Lothumalla S, Yama I, Burks JK, Gomez J, Rao X, Wang J, Woodman K, Mansour J, Arenkiel B, Osman KL, Haxton C, Lever TE, Hutcheson KA, Amit M (2024) Neural landscape is associated with functional outcomes in irradiated patients with oropharyngeal squamous cell carcinoma. Sco Transl Med 16:eabq5585. doi: 10.1126/scitranslmed.abq5585

Objective: To understand the correlation between neuronal changes and patient-reported and functional outcomes in patients with oropharyngeal squamous cell carcinoma (OPSCC).

Summary: Tumor enrichment of adrenergic (TH+) and CGRP+ sensory–afferent nerves correlated with poorer swallowing outcomes. Functional electromyography recordings showed correlations between growing (GAP43+) and immature cholinergic (ChAT+DCX+) nerves and denervation patterns in survivors of OPSCC. A murine model of radiation-induced dysphagia further confirmed that immature cholinergic and CGRP+ nerves were correlated with impaired swallowing. The results suggest that CGRP+ and ChAT+ neuronal signaling play distinct roles in tumor- and radiation-induced dysphagia in OPSCC and offer a comprehensive dataset on the neural landscape of OPSCC.

Usage: 500 μg in 3 μl of alpha-CGRP-streptavidin-saporin (CGRP-SAP; #IT-94) and anti-ChAT-SAP (#IT-42) was stereotactically injected into the intraganglionic region over 3 min.

Related Products: CGRP-SAP (Cat. #IT-94), Anti-ChAT-SAP (Cat. #IT-42)

Kwok CHT, Harding EK, Burma NE, Markovic T, Massaly N, van den Hoogen NJ, Stokes-Heck S, Gambeta E, Komarek K, Yoon HJ, Navis KE, McAllister BB, Canet-Pons J, Fan C, Dalgarno R, Gorobets E, Papatzimas JW, Zhang Z, Kohro Y, Anderson CL, Thompson RJ, Derksen DJ, Morón JA, Zamponi GW, Trang T (2024) Pannexin-1 channel inhibition alleviates opioid withdrawal in rodents by modulating locus coeruleus to spinal cord circuitry. Nat Commun 15(1):6264. doi: 10.1038/s41467-024-50657-7 PMID: 39048565

Objective: To show that pannexin-1 (Panx1) channels expressed on microglia critically modulate LC activity during opioid withdrawal.

Summary: The findings demonstrate that microglial Panx1 channels modulate LC noradrenergic circuitry during opioid withdrawal and reinstatement. Blocking Panx1 to dampen LC hyperexcitability may, therefore, provide a therapeutic strategy for alleviating the physical and aversive components of opioid withdrawal.

Usage: Mac-1-SAP (IT-06) was injected through the cannula (15 µg) for three consecutive days before systemic naloxone administration.

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

Su Y, Xu J, Zhu Z, Chin J, Xu L, Yu H, Nudell V, Dash B, Moya EA, Ye L, Nimmerjahn A, Sun X (2024) Brainstem Dbh+ neurons control allergen-induced airway hyperreactivity. Nature 631(8021):601-609. doi: 10.1038/s41586-024-07608-5 PMID: 38987587

Objective: To map a full allergen circuit from the lung to the brainstem and back to the lung. Repeated exposure of mice to inhaled allergen activated the nuclei of solitary tract (nTS) neurons in a mast cell-, interleukin-4 (IL-4)- and vagal nerve-dependent manner.

Summary: Ablation or chemogenetic inactivation of Dbh+nTS neurons blunted hyperreactivity whereas chemogenetic activation promoted it. Viral tracing indicated that Dbh+nTS neurons project to the nucleus ambiguous (NA) and that NA neurons are necessary and sufficient to relay allergen signals to postganglionic neurons that directly drive airway constriction. Delivery of noradrenaline antagonists to the NA blunted hyperreactivity, suggesting noradrenaline as the transmitter between Dbh+nTS and NA.

Usage: To determine whether Dbh+nTS neurons are essential for hyperreactivity chemical ablation, anti-dopamine beta-hydroxylase antibody conjugated to saporin (Anti-DBH-SAP, IT-03), shown to be specific for DBH+neurons, was injected into the nTS.

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