References

Sainz AE (2023) The effects of loss of orexin neurons on attention. William & Mary Thesis.

Objective: This paper examines the effects of loss of orexin neurons on attention in mice.

Summary: This undergraduate honors thesis from William & Mary tested attention in mice after selective loss of orexin neurons, which are important for arousal. The researchers found impairments in sustained attention and cognitive flexibility in the mice missing orexin neurons.

Usage: 0.5 µl of Orexin-B-SAP (0.4 µg/µl) or saline was administered to both sides of the lateral hypothalamus for 30 seconds using a 1 µl syringe.

Related Products: Orexin-B-SAP (Cat. #IT-20)

Choi P (2023) The VLM a1/c1 ca/npy neuronal projections to the perifornical area of the lateral hypothalamus and its functional role in glucoprivic feeding. Washington State Univ Thesis.

Objective: This dissertation aimed to determine the role of neuropeptide Y (NPY) receptor signaling from the ventrolateral medulla (VLM) catecholamine (CA) neurons in the lateral hypothalamus (LHA) for glucoprivic feeding.

Summary: The results showed that NPY receptor-expressing neurons in the perifornical area of the LHA are required for glucoprivic feeding evoked by 2-deoxyglucose. Furthermore, antagonism of NPY Y1 or Y2 receptors in the LHA attenuated feeding evoked by chemogenetic activation of VLM CA neurons, indicating NPY release from VLM neurons activates LHA NPY receptors to elicit glucoprivic feeding.

Usage: NPY-SAP (50 ng per 100 nL/site) or control Blank-SAP (50 ng per 100 nL/site) dissolved in 0.01 M phosphate buffer was infused slowly over a 5 minute period directly into the perifornical lateral hypothalamic (stereotaxic coordinate: 2.8 mm caudal from bregma, +/- 1.2 mm lateral to the midline, and -7.4 mm from the dura mater) through a pulled glass capillary pipette (30 µm tip diameter) connected to a Picospritzer. The rats were allowed at least 7 days for a full recovery from surgery and NPY-SAP-induced neuronal ablation.

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

Zhou Y, Zhang K, Wang F, Chen J, Chen S, Wu M, Lai M, Zhang Y, Zhou W (2023) Polypyrimidine tract binding protein knockdown reverses depression-like behaviors and cognition impairment in mice with lesioned cholinergic neurons. Front Aging Neurosci 15:1174341. doi: 10.3389/fnagi.2023.1174341 PMID: 37181622

Objective: Examine the mechanisms of how knockdown of the RNA-binding protein polypyrimidine tract binding protein (PTB) reverses depression-like behavior and cognition impairment in mice with lesioned cholinergic neurons.

Summary: A specific loss of cholinergic neurons in the horizontal limb of the diagonal band of broca (HDB) is correlated with depression and dysfunction of cognition in mice. The authors induced cholinergic neuron loss via injection of 192-IgG-SAP. This was followed by injection of either antisense oligonucleotides or adeno-associated virus-shRNA in the injured area of HDB to knockdown PTB. Knockdown of PTB by these two approaches was found to relieve depression-like behaviors and alleviate cognitive impairment and the findings suggest that supplementing cholinergic neurons after PTB knockdown may be a therapeutic approach to reverse depression-like behaviors and cognitive impairment.

Usage: 192 IgG-saporin (Cat. IT-01) was injected bilaterally into the HDB at a volume of 0.25 μl with a concentration of 1 μg/μL, per side.

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

Wu D, Yu N, Gao Y, Xiong R, Liu L, Lei H, Jin S, Liu J, Liu Y, Xie J, Liu E, Zhou Q, Liu Y, Li S, Wei L, Lv J, Yu H, Zeng W, Zhou Q, Xu F, Luo MH, Zhang Y, Yang Y, Wang JZ (2023) Targeting a vulnerable septum-hippocampus cholinergic circuit in a critical time window ameliorates tau-impaired memory consolidation. Mol Neurodegener 18(1):23. doi: 10.1186/s13024-023-00614-7 PMID: 37060096

Objective: There is an urgent need to study the targeting strategy for the MS-hippocampus cholinergic pathway to rescue tau-impaired memory.

Summary: Abnormal tau accumulation and cholinergic degeneration are hallmark pathologies in the brains of patients with Alzheimer’s disease (AD). However, the sensitivity of cholinergic neurons to AD-like tau accumulation and strategies to ameliorate tau-disrupted spatial memory in terms of neural circuits still remain elusive. The authors found that cholinergic neurons with an asymmetric discharge characteristic in the MS-hippocampal CA1 pathway are vulnerable to tau accumulation. Photoactivating MS-CA1 cholinergic inputs within a critical 3 h time window during memory consolidation efficiently improved tau-induced spatial memory deficits in a theta rhythm dependent manner. 192-IgG-Saporin was used to create an Alzheimer’s Disease animal model.

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

See Also:

• Dornan WA et al. Comparison of site-specific injections into the basal forebrain on water maze and radial arm maze performance in the male rat after immunolesioning with 192 IgG saporin. Behav Brain Res 82:93-101, 1996.

Yaksh TL, dos Santo G, Lemes J, Malange K (2023) Neuraxial drug delivery in pain management: An overview of past, present, and future. Anaesthesiology 37(2):243-265. doi: 10.1016/j.bpa.2023.04.003 PMID: 37321769

Objective: Review of neuraxial therapeutic delivery platforms for pain management and the regulation caused by pharmacological targeting of dorsal root ganglion and dorsal horn systems.

Summary: Studies have shown modulation by spinal opiates, but subsequent work reveals the complexity of the neuraxial system. Various delivery platforms, such as viral transfection, antisense and targeted neurotoxins give evidence to approaches to selectively address the acute and chronic pain phenotype. Substance P-Saporin is discussed as a method to lesion NK1R-containing neurons for the treatment of chronic pain.

Related Products: SP-SAP (Cat. #IT-07)

See Also:

• Wiese AJ et al. Intrathecal substance p-saporin in the dog: distribution, safety, and spinal neurokinin-1 receptor ablation. Anesthesiology 119(5):1163-1177, 2013.
• Brown DC et al. Intrathecal substance p-saporin in the dog: efficacy in bone cancer pain. Anesthesiology 119(5):1178-1185, 2013.
• Wiley RG Substance P receptor-expressing dorsal horn neurons: Lessons from the targeted cytotoxin, substance P-saporin. Pain 136:7-10, 2008.

Singh SA, Vellapandian C (2023) The promising guide to LC–MS analysis and cholinesterase activity of Luffa cylindrica (L.) fruit using in vitro and in-silico analyses. Futur J Pharm Sci 9:33. doi: 10.1186/s43094-023-00478-0

Objective: Identify and analyze the extract of the plant Luffa cylindrica for bioactive and biochemical properties, particularly as it relates to bioactivity in neurological diseases.

Summary: Luffa cylindrica contains a total of 80 compounds that were identified in the ethanolic extract from LC–MS analysis. The bioactive compounds were screened for activity in receptors responsible for causing oxidative stress-associated Alzheimer’s disease. Perlolyrine was chosen to perform in-silico docking. An in vitro activity of cholinesterase showed highest inhibition at 500 μg/ml. In-silico docking of perlolyrine showed better binding affinity and score. Results revealed that out of 10 docked receptors, amyloid beta showed the highest binding affinity with an energy of −46.1 kcal/mol showing promising drug for Alzheimer’s disease. The study reports the presence of a promising, bioactive compound (perlolyrine) with promisng applications in vivo, oxidative stress-related Alzheimer’s disease.

Related Products: Saporin (Cat. #PR-01)

See Also:

• Santosh et al (2015) Mechanism of Anti-HIV Activity of Ribosome Inactivating Protein, Saporin. Protein & Peptide Letters. 22(6): 497-503. doi: 10.2174/0929866522666150428120701

Karthikeyan R, Davies WIL, Gunhaga L (2023) Non-image-forming functional roles of OPN3, OPN4 and OPN5 photopigments. J Photochem Photobiol 15:100177. doi: 10.1016/j.jpap.2023.100177

Objective: To review recent studies that focus on the non-image-forming functional roles of the OPN3, OPN4, and OPN5 photopigments.

Summary: This publication explores the non-image-forming functions of OPN3, OPN4, and OPN5 photopigments, highlighting their roles in various physiological processes such as regulation of circadian rhythms, pupillary light responses, modulation of sleep, mood, and hormone secretion, providing insights into the diverse functions of these photopigments beyond vision.

Related Products: Melanopsin-SAP (Cat. #IT-44)

Ren X, Liu S, Virlogeux A, Kang SJ, Brusch J, Liu Y, Dymecki SM, Han S, Goulding M, Acton D (2023) Identification of an essential spinoparabrachial pathway for mechanical itch. Neuron 30:S0896-6273. doi: 10.1016/j.neuron.2023.03.013 PMID: 37023756

Objective: Study pathways of mechanical and chemical itch.

Summary: Mechanical and chemical itch are controlled by separate pathways within the body. Gpr83ligand PEN peptide conjugated to saporin (PEN-SAP) was used to selectively ablate CAlcrl projection neurons, alleviating mechanical itch sensitivity in wild-type mice. Substance-P saporin (SSP-SAP) was injected into mice and used as a negative control for the ablation of itch-sensitive neurons in the areas targeted. The ablated mice maintained mechanical itch sensitivity.

Usage: Intrathecal injections of SSP-SAP (IT-11; 100 ng/10 ml 0.9% sterile saline), biotinylated Gpr83 ligand (PEN) conjugated to Strepavidin-ZAP (IT-27), PEN-SAP, 3 ug/10 ml, 0.9% sterile saline, or control Blank-SAP (IT-21) in mice.

Related Products: SSP-SAP (Cat. #IT-11), Streptavidin-ZAP (Cat. #IT-27), Blank-SAP (Cat. #IT-21)

Son H, Shin J, Park J (2023) Recent progress in nanomedicine-mediated cytosolic delivery. RSC Adv 13(15):9788-9799. doi: 10.1039/D2RA07111H PMID: 36998521

Summary: Cytosolic delivery of drugs, like saporin, through nanocapsules offers ways to move proteins through the body with greater specificity and efficacy. A nanoparticle that released a modified saporin protein at pH conditions correlative conditions to a tumor micro-environment was discussed as a model to deliver peptide-drugs to the cytosol.

Nestor CC, Merkley CM, Lehman MN, Hileman SM, Goodman RL (2023) KNDy neurons as the GnRH pulse generator: Recent studies in ruminants. Peptides 164:171005. doi: 10.1016/j.peptides.2023.171005 PMID: 36990389

Objective: This publication aims to summarize and provide an overview of recent studies investigating the role of KNDy neurons as the pulse generator for gonadotropin-releasing hormone (GnRH) release in ruminants.

Summary: Recent studies in ruminants, specifically sheep and cows, have investigated the role of KNDy neurons in driving the pulsatile release of GnRH. These studies have demonstrated the rhythmic electrical activity of KNDy neurons, coinciding with the pulsatile secretion of GnRH in ewes, suggesting their central role as the pulse generator. Additionally, the expression patterns of genes related to KNDy neurons and GnRH pulsatility have been examined in cows, revealing variations throughout the estrous cycle and indicating a potential involvement of KNDy neurons in regulating GnRH release in this species. These findings contribute to our understanding of reproductive physiology in ruminants and have implications for both animal and human reproductive health.

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