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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):797-811. 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)
Distinct cholinergic circuits underlie discrete effects of reward on attention. Front Mol Neurosci
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)
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Role of the locus coeruleus arousal promoting neurons in maintaining brain criticality across the sleep-wake cycle
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)
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):831-845. doi: 10.1007/s13346-024-01698-4 PMID: 39196501
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)
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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)
A cocktail of engineered chimeric antibodies targeting the central nervous system produces a broad-spectrum therapeutic effect for symptomatic rabies
Zhao L, Ren Z, Wang C, Wang H, Wu Q, Hou Q, Qi X, He W, Zhang X, Wan J , Zhoui M, Fu Z (2024) A cocktail of engineered chimeric antibodies targeting the central nervous system produces a broad-spectrum therapeutic effect for symptomatic rabies. Research Square preprint. doi: 10.21203/rs.3.rs-4838561/v1
Objective: To construct and assess four chimeric human-mouse antibodies with high neutralizing activity and affinity against rabies virus (RABV), further identifying their targeted antigenic epitopes as I, II, and IV.
Summary: Results showed that combined treatment of RABV-infected mice with three SynB1-antibodies targeting different epitopes could reduce clinical symptoms and increase survival ratio to 80%. Collectively, the non-invasive brain delivery method based on hybrid antibody-conjugated cell-penetrating peptides offers a promising strategy for the effective treatment of broad-spectrum symptomatic rabies.
Usage: Saporin was suggested as a payload for SynB1 antibodies based on researchers who investigated the use of THR peptides targeting transferrin receptor protein 1 (TFR1) conjugated with drugs for the treatment of Alzheimer’s disease, APOE peptides attached to Saporin (PR-01) to target low-density lipoprotein receptor (LDLR) for glioma therapy, and the TGN peptide-Saporin, which has been studied in the field of epilepsy.
Related Products: Saporin (Cat. #PR-01)
See Also:
- Daniels-Wells TR et al. Insights into the mechanism of cell death induced by saporin delivered into cancer cells by an antibody fusion protein targeting the transferrin receptor 1. Toxicol In Vitro 27(1):220-231, 2013.
- Branco F et al. Peptide-hitchhiking for the development of nanosystems in glioblastoma. ACS Nano 18(26):16359-16394, 2024.
- Thankachan S et al. Ventrolateral periaquaductal gray (vlPAG): Key area for REM sleep propensity. Neuroscience 2008 Abstracts 586.3/SS36, 2008. Society for Neuroscience, Washington, DC
Characterization of MAP c21873-1 as a new counter-selectable marker for unmarked genetic modification of Pichia pastoris
Liu M, Zhou S, Cao Y, Yang K, Xiao Y, Wang W (2024) Characterization of MAP c21873-1 as a new counter-selectable marker for unmarked genetic modification of Pichia pastoris. Microb Cell Fact 23(1):224. doi: 10.1186/s12934-024-02496-w PMID: 39118053
Objective: To establish a new counter-selectable marker-based strategy for seamless modification with high efficiency and low toxicity.
Summary: Development of MAP c21873-1 as a novel counter-selectable marker which could perform efficient gene knock-in by site-directed HR.
Usage: MazF, c21873-1, c23467 and twenty-four RIPs were selected to construct a phylogenetic tree to investigate their relationships in the evolutionary history. The phylogenetic analysis demonstrates that c21873-1 and c23467 are closely relative to type I RIPs such as PAP-S and saporin (PR-01).
Related Products: Saporin (Cat. #PR-01)
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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)
Navigating the neurological frontier: Macromolecular marvels in overcoming blood-brain barrier challenges for advanced drug delivery
Zeynalzadeh E, Khodadadi E, Khodadadi E, Ahmadian Z, Kazeminava F, Rasoulzadehzali M, Samadi Kafil H (2024) Navigating the neurological frontier: Macromolecular marvels in overcoming blood-brain barrier challenges for advanced drug delivery. Heliyon 10(15):e35562. doi: 10.1016/j.heliyon.2024.e35562 PMID: 39170552
Objective: To understand how nanoparticles interact with the blood-brain barrier.
Summary: Enhancing the bioavailability of nano formulations at the intended site is critical. The use of surface ligands that target brain endothelial cell receptors may improve BBB penetration. In summary, nanomaterials offer vast potential in the realm of brain-targeted therapies, from early detection to effective treatment.
Usage: Saporin (PR-01) was cited for protein toxin delivery as a therepeutic agent for BBB penetration.
Related Products: Saporin (Cat. #PR-01)
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