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Cognitive and histopathological alterations in rat models of early- and late-phase memory dysfunction: Effects of sigma-1 receptor activation
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)
Plant-derived extracellular vesicles: a synergetic combination of a drug delivery system and a source of natural bioactive compounds
Langellotto MD, Rassu G, Serri C, Demartis S, Giunchedi P, Gavini E (2024) Plant-derived extracellular vesicles: a synergetic combination of a drug delivery system and a source of natural bioactive compounds. Springer Nature 11(3) doi: 10.1007/s13346-024-01698-4
Objective: This review intends to provide adequate tools for studying and developing drug delivery systems based on plant-derived extracellular vesicles (EVs).
Summary: Freeze-drying could be useful for preserving plant-derived exosomes at higher temperatures without affecting their size, morphology or other parameters. Still, it may reduce protein activity, as reported by Noguchi and coworkers, who observed a diminished biological activity of protein saporin after its encapsulation in EVs and freeze-drying.
Related Products: Saporin (Cat. #PR-01)
See Also:
From past to future: 50 years of pharmacological interventions to treat narcolepsy
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.
A thalamic nucleus reuniens-lateral septum-lateral hypothalamus circuit for comorbid anxiety-like behaviors in chronic itch
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)
Modulating amacrine cell-derived dopamine signaling promotes optic nerve regeneration and preserves visual function
Zhang Q, Xue J, Tang J, Wu S, Liu Z, Wu C, Liu C, Liu Y, Lin J, Han J, Liu L, Chen Y, Yang J, Li Z, Zhao L, Wei Y, Li Y, Zhuo Y (2024) Modulating amacrine cell-derived dopamine signaling promotes optic nerve regeneration and preserves visual function. Sci Adv 10(31):eado0866. doi: 10.1126/sciadv.ado0866 PMID: 39093964
Objective: To identify a unique subtype of amacrine cells (ACs), dopaminergic ACs (DACs), that respond early to optic nerve crush by downregulating neuronal activity and reducing retinal dopamine (DA) release.
Summary: Activation of DACs or augmentation of DA release using levodopa demonstrated neuroprotective effects and modestly enhanced axon regeneration. The dopamine receptor D1 (DRD1) was also identified as a critical mediator of DAC-derived DA, and retinal ganglion cell (RGC)-specific DRD1 overexpression effectively overcame subtype-specific barriers to regeneration.
Usage: Immunostaining of retinal cryosections and whole mounts (1:1000) (AB-N39).
Related Products: Melanopsin Rabbit Polyclonal, affinity-purified (Cat. #AB-N39)
Neural landscape is associated with functional outcomes in irradiated patients with oropharyngeal squamous cell carcinoma
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)
Longitudinal intravascular antibody labeling identified regulatory t cell recruitment as a therapeutic target in a mouse model of lung cancer
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
Related Products: Anti-CD25-SAP mouse (Cat. #IT-29)
Pannexin-1 channel inhibition alleviates opioid withdrawal in rodents by modulating locus coeruleus to spinal cord circuitry
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)
Brainstem Dbh+ neurons control allergen-induced airway hyperreactivity
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)
A non-invasive stem cell therapy boosts lymphopoiesis and averts age-related blood diseases in mice
Bryder D, Konturk-Ciesla A, Zhang Q, Kharazi S (2024) A non-invasive stem cell therapy boosts lymphopoiesis and averts age-related blood diseases in mice. Research Square doi: 10.21203/rs.3.rs-4528815/v1
Objective: To develop a murine transplantation model based on low-intensity conditioning protocols using antibody-mediated Hematopoietic stem cell.
Summary: Authors demonstrate that young HSCs, once transplanted, survive and thrive in aged hosts, dramatically improving hematopoietic output and ameliorating age-compromised lymphopoiesis.
Usage: Intravenous injection of CD45-SAP (3 mg/kg, IT-91). Biotinylated anti-CD45.2 antibodies were mixed with streptavidin-saporin conjugate at a 1:1 molar ratio (IT-27).
Related Products: Anti-CD45.2-SAP (Cat. #IT-91), Streptavidin-ZAP (Cat. #IT-27)
