Chamberlain AR, Huynh L, Huang W, Taylor DJ, Harris ME (2023) The specificity landscape of bacterial ribonuclease P. J Biol Chem 300(1):105498. doi: 10.1016/j.jbc.2023.105498 PMID: 38013087
Objective: Review of the specificity of ribonucleoprotein RNase P in binding different types of RNA.
Summary: Ribonucelase P is involved in the RNA metabolism pathways. By studying the rate at which it combines with different types of RNA under different conditions, like concentration and competition with different enzymes, a model describing its specificity to different RNA motifs can be developed.
Kirkey DC, Robinson L, Janssens D, Hines MG, Hylkema T, Manselle MK, Ries RE, Peplinski JH, Wallace LK, Otto D, Tarlock K, Henikoff S, Li W, Meshinchi S (2023) CLEC2A is a novel AML-restricted immunotherapeutic target enriched in KMT2A-rearranged acute myeloid leukemia. Blood 142(1):290. doi: 10.1182/blood-2023-188439
Objective: Targeting CLEC2A, a novel immunotherapeutic target, in the treatment of acute myeloid leukemia.
Summary: CLEC2A, a novel immunotherapeutic target expressed highly in acute myeloid leukemia, is a potential target in treating leukemia. By conjugating an antibody targeting this protein to saporin, an ADC for the treatment of leukemia can be created.
Usage: A CLEC2A-antibody was conjugated to Hum-ZAP [IT-22] and treated against CLEC2A+ and CLEC2A- cells and target-specific cytotoxicity was observed at 10nM levels.
Zlatkovic J, Dalmau Gasull A, Hägg D, Font-Gironès F, Bellman J, Meister B, Palsdottir V, Ruud J, Ohlsson C, Dickson SL, Anesten F, Jansson JO (2023) Reduction of body weight by increased loading is associated with activation of norepinephrine neurones in the medial nucleus of the solitary tract. J Neuroendocrinol 35(12):e13352. doi: 10.1111/jne.13352 PMID: 37885347
Objective: To show that the feed-back regulation of body weight, initiated by a novel leptin-independent body weight homeostat, involves a CNS mechanism
Summary: In conclusion, increased load appears to reduce body weight and food intake via activation of norepinephrine neurones in the medial nucleus of the solitary tract.
Usage: 5 ng of Anti-DBH-SAP (IT-03) was bilaterally injected into the NTS in Male C57/B6J mice and Sprague–Dawley rats.
Gamage R, Rossetti I, Niedermayer G, Münch G, Buskila Y, Gyengesi E. (2023) Chronic neuroinflammation during aging leads to cholinergic neurodegeneration in the mouse medial septum. J Neuroinflammation 20(1):235. doi: 10.1186/s12974-023-02897-5 PMID: 37833764
Summary: This publication presents the findings of studies on age-related cholinergic decline. The authors mention a diffusion MRI study that documented a 25% reduction in the BFCN (Basal Forebrain Cholinergic Neurons) population and a significant loss of terminal cholinergic projections in the hippocampus after inducing selective BFCN degeneration in mice using mu p75-SAP.
Objective: To review and discuss the roles of spinal sensory pathways, specifically dorsal root ganglia (DRG) afferents, in energy balance regulation, highlighting their contributions to metabolic homeostasis in health and disease.
Summary: This comprehensive review explores the emerging significance of spinal sensory neurons, beyond traditional gut-brain and adipose tissue-to-brain signaling pathways, in regulating energy intake and metabolism. It delves into the anatomy and functions of spinal sensory pathways, emphasizing the potential of DRG afferents in providing metabolic information to the brain. The review suggests that identifying specific DRG neurons and understanding their molecular mechanisms are crucial steps toward developing targeted therapies for metabolic diseases, such as obesity, diabetes, and cancer.
Usage: The publication references that CCK-SAP (IT-31) injected into the nodose ganglia of mice and rats selectively ablates vagal afferent neurons expressing CCKA receptors.
Aquino NSS, Campideli-Santana AC, Antunes LM, Araújo-Lopes R, da Costa Silva KS, Costa Henriques P, de Oliveira Gusmão D, Bernuci MP, Szawka RE, dos Reis AM (2023) Partial loss of KNDy neurons in prenatally androgen treated female rats alters the LH secretion and ovarian morphology in a model of polycystic ovary syndrome. J Endocrine Society 7(S1):bvad114.1215. doi: 10.1210/jendso/bvad114.1215
Objective: To examine the impact of partial loss of KNDy neurons in prenatally androgen-treated female rats on luteinizing hormone (LH) secretion and ovarian morphology, as a model of polycystic ovary syndrome (PCOS).
Summary: The study found that the ablation of KNDy neurons resulted in increased LH pulse amplitude and mean LH levels without affecting pulse frequency, and partially restored the number of primordial follicles, suggesting KNDy neurons’ role in modulating LH release and ovarian reserve in PCOS.
Usage: Intra-ARC stereotaxic injections of the neurokinin-3 receptor agonist conjugated with Saporin (NKB-SAP, IT-63) to induce the lesion of KNDy neurons. Blank-SAP (IT-21) was used as a control.
Campideli-Santana AC, da Costa Silva KS, Araújo-Lopes R, Antunes LM, Szawka RE (2023) Submaximal loss of KNDy neurons accelerates and amplifies pulsatile LH secretion in female rats. J Endocrine Society 7(S1):bvad114.1214. doi: 10.1210/jendso/bvad114.1214
Objective: To investigate the impact of the submaximal loss of KNDy neurons on the pulsatile secretion of luteinizing hormone (LH) in female rats.
Summary: The study found that a partial loss of these neurons led to irregular estrous cycles and increased frequency and amplitude of LH pulses. This suggests a new role for KNDy neurons in moderating LH pulse frequency and amplitude in ovary-intact animals, with implications for early antral follicle recruitment.
Usage: Adult female rats underwent a neurochemical ablation of KNDy neurons via intra-ARC stereotaxic injections of NKB-SAP (IT-63), while control animals received Blank-SAP (IT-21).
Nie Y, Liang J, Sun J, Li J, Zhai X, Zhao P (2023) Orexin A alleviates LPS-induced acute lung injury by inhibiting macrophage activation through JNK-mediated autophagy. Int Immunopharmacol 124(Pt B):111018. doi: 10.1016/j.intimp.2023.111018 PMID: 37801969
Objective: To investigate the crosstalk between the central nervous system and immune response through the inflammatory response caused by lung injury.
Summary: By modeling acute respiratory distress in mice, the role of orexin-A and orexin-B was investigated through their inflammatory response. Orexin neurons were eliminated through lesions with Orexin-B-SAP (IT-20). Inflammatory cell infiltration and pro-inflammatory cytokines generation were aggravated after orexin neurons were ablated.
Usage: Mice were injected in the bilateral hypothalamus with 1 μL of Orexin-B-SAP (0.36 μg/μL) using a permanent stainless steel internal cannula connected at a speed of 16.5 ng/23 nl/second.
Goodman RL, Moore AM, Onslow K, Hileman SM, Hardy SL, Bowdridge EC, Walters BA, Agus S, Griesgraber MJ, Aerts EG, Lehman MN, Coolen LM (2023) Lesions of kndy and kiss1r neurons in the arcuate nucleus produce different effects on lh pulse patterns in female sheep. Endocrinology 164(11):bqad148. doi: 10.1210/endocr/bqad148 PMID: 37776515
Objective: To test the functional role of ovine KNDy neurons in pulse generation and identify the roles of nearby Kiss1 receptor (Kiss1R)-containing cells.
Summary: Injection of NK3-SAP (NKB-SAP) ablated over 90% of the KNDy cells, Kiss-SAP lesioned about two-thirds of the Kiss1R population. This led to a significant decrease in LH pulse amplitude and altering LH pulse patterns. NK3-SAP increased the interpulse interval without affecting the regularity of LH pulses, whereas Kiss-SAP disrupted their regular hourly occurrence but not the interpulse interval. The findings suggest that KNDy neurons are critical for GnRH pulse generation in ewes, while ARC Kiss1R cells support the amplitude and regularity of these pulses, possibly as part of a positive feedback loop involving GABA or glutamate.
Usage: Saporin conjugates were injected into the arcuate nucleus. Kiss-SAP (kisspeptin54-SAP) was diluted to 700 ng/μL in PBS immediately before use. In preliminary work to test the effectiveness of Kiss-SAP, a single unilateral injection (1 μL of 700 ng/μL) of this conjugate was made in the preoptic area of 3 ewes. The contralateral side was used as control and either received no injections or Blank-SAP (1 μL of 700 ng/μL) (IT-21).
Gao Q, Zhang Y, Wang X, Wang R, Zhang L (2024) Regulation of nociception threshold by norepinephrine through adrenergic α2 receptor in rat models of Parkinson’s disease. CNS Neurosci Ther 30(3):e14446. doi: 10.1111/cns.14446 PMID: 37721421
Objective: To investigate the effect of norepinephrine on the activation of brain cells through adrenergic α2 receptor, to regulate the nociception threshold in a 6-OHDA-induced animal model of Parkinson’s disease (PD).
Summary: The change of norepinephrine content can affect the activation of prefrontal and cingulate gyrus glial cells and participate in the regulation of nociception threshold in PD rats. Adrenergic α2 receptor agonist and central presynaptic membrane α2 receptor blocker both affect cell activation and improve hyperalgesia.
Usage: 4 μL of Anti-DBH-saporin was injected into the right lateral ventricle (1.25 μg/μL, 0.9% NaCl dilution), and injected at the rate of 1 μL/min.
