Crevier-Sorbo G, Rymar, VV,Crevier-Sorbo R, Sadikot AF (2020) Thalamostriatal degeneration contributes to dystonia and cholinergic interneuron dysfuntion in a mouse model of huntington’s disease. Acta Neruopatho Commun 8(1):14. doi: 10.1186/s40478-020-0878-0 PMID: 32033588
Objective: To ablate the neurons of the Thalamostrial system (TS) to elucidate their role in the motor symptoms of Huntington’s Disease.
Summary: Huntington’s disease is an autosomal disorder characterized by involuntary movement and striatal neuronal loss. Glutaminergic input from the TS is implicated in disease progression and motor deficits. Anti-ChAT-SAP is used to ablate neurons in the Thalamostrial system to understand the role these neurons played in Huntington’s.
Usage: Mice underwent unilateral, striatal injections with either Anti-ChAT-SAP (IT-42) or Rabbit IgG-SAP (IT-35). The total volume and concentration of either saporin construct was the same (0.7 μL of 0.6 μg/μL solution).
Kelly SC, McKay EC, Beck JS, Collier TJ, Dorrance AM, Counts SE (2019) Locus coeruleus degeneration induces forebrain vascular pathology in a transgenic rat model of alzheimer’s disease. J Alzheimers Dis 70(2):371-388. doi: 10.3233/JAD-190090 PMID: 31177220
Objective: To understand the extent to which locus coeruleus projection system degeneration influences vascular pathology.
Summary: Noradrenergic locus coeruleus (LC) neuron loss is a significant feature of mild cognitive impairment and Alzheimer’s disease (AD). The authors stereotactically lesioned LC projection neurons innervating the prefrontal cortex of six-month-old Tg344–19 AD rats using DBH-SAP, or an untargeted control IgG-SAP. DBH-sap-lesioned animals performed significantly worse than IgG-sap animals on the Barnes maze task in measures of both spatial and working memory. DBH-sap-lesioned rats also displayed increased amyloid and inflammation pathology compared to IgG-sap controls. Results indicate that LC projection system degeneration is a nexus lesion that compromises both vascular and neuronal function in cognitive brain areas during the prodromal stages of AD.
Usage: Anti-DBH-SAP (IT-03) or control Mouse IgG-sap (IT-18) were administered to the PFC bilaterally ( 2.5 μg/injection).
Goodman RL, He W, Lopez JA, Bedenbaugh MN, McCosh RB, Bowdridge EC, Coolen LM, Lehman MN, Hileman SM (2019) Evidence that the LH surge in ewes involves both neurokinin B–dependent and –independent actions of kisspeptin. Endocrinology 160(12):2990-3000. doi: 10.1210/en.2019-00597
Objective: To determine if NKB is involved in the RCh of the ewe in the LH surge.
Summary: NKB signaling in the RCh increases kisspeptin levels critical for the full amplitude of the LH surge in the ewe, but kisspeptin release occurs independently of retrochiamatic area (RCh) input at the onset of the surge to initiate GnRH secretion.
Usage: Bilaterial injections in the RCh of either NK3-SAP or Blank-SAP.
Tominaga M, Kusube F, Honda K, Komiya E, Takahashi N, Naito H, Suga Y, Takamori K (2019) OP11: Role of spinal cholecystokinin receptor 2 in alloknesis models. Itch 4:1-62. doi: 10.1097/itx.0000000000000030
Objective: To determine the detailed molecular and cellular mechanisms that induce alloknesis via the spinal CCK2 receptor.
Summary: Ablation of spinal CCK receptor-expressing cells by i.t. injection of CCK-SAP attenuated CCK8S-induced alloknesis in comparison with Blank-SAP control mice.
Seamon M, Ahn W, Li AJ, Ritter S, Harris RBS (2019) Leptin receptor-expressing neurons in ventromedial nucleus of the hypothalamus contribute to weight loss caused by fourth ventricle leptin infusions. Am J Physiol Endocrinol Metab 317(4):E586-E596. doi: 10.1152/ajpendo.00205.2019
Objective: To test the importance of VMH leptin responsiveness in mediating weight loss caused by fourth ventricle leptin infusion.
Summary: Leptin did not inhibit food intake and respiratory exchange ratio in rats treated with Leptin-SAP. VMH leptin receptors do not play a significant role in maintaining energy balance in basal conditions, but limit weight gain during positive energy balance.
Usage: Bilateral VMH 75-nl injections of 260 ng/ml of Leptin-SAP or Blank-SAP.
Pan H, Fatima M, Li A, Lee H, Cai W, Horwitz L, Hor CC, Zaher N, Cin M, Slade H, Huang T, Xu XZS, Duan B (2019) Identification of a spinal circuit for mechanical and persistent spontaneous itch. Neuron 103(6):1135-1149.e6. doi: 10.1016/j.neuron.2019.06.016
Objective: To identify a spinal circuit for mechanical and persistent spontaneous itch.
Summary: Findings indicate excitatory interneurons expressing Urocortin 3::Cre (Ucn3+) in the dorsal spinal cord as a valid cellular target for future therapeutic interventions against chronic itch, without affecting normal touch.
Usage: To ablate spinal GRPR+ neurons, mice were given a single intrathecal injection of either Bombesin-SAP or Blank-SAP (400 ng in 10 mL sterile saline). To ablate spinal Npra+ neurons, mice were given a single intrathecal injection of either Nppb-SAP or Blank-SAP (5 mg in 10 mL sterile saline).
Katsurada K, Nakata M, Saito T, Zhang B, Maejima Y, Nandi SS, Sharma NM, Patel KP, Kario K, Yada T (2019) Central glucagon-like peptide-1 receptor signaling via brainstem catecholamine neurons counteracts hypertension in spontaneously hypertensive rats. Sci Rep 9(1):12986. doi: 10.1038/s41598-019-49364-x
Objective: To determine mechanisms for antihypertensive effect of GLP-1R agonists.
Summary: The central GLP-1R signaling via NTS DBH neurons counteracts the development of hypertension in SHR, accompanied by attenuated sympathetic nerve activity.
Usage: Anti-DBH-SAP or Blank-SAP was injected into NTS bilaterally (6 ng/200 nl).
Maejima Y, Yokota S, Horita S, Shimomura K (2019) The undeveloped properties of GABA neurons in the ventral tegmental area promote energy intake for growth in juvenile rats. Sci Rep 9(1):11848. doi: 10.1038/s41598-019-48336-5
Objective: To determine the underlying mechanisms that induce high energy intake (EI) per body weight (BW).
Summary: Undeveloped properties of VTA GABA neurons in juvenile rats can promote higher EI regardless of high or less palatable feeding, and contribute to growth promotion.
Usage: GAT1-SAP or control, Rabbit IgG-SAP, was bilaterally injected (0.025 μg/0.5 μl) into the VTA in eight-week-old adult rats.
Sakata D, Uruno T, Matsubara K, Andoh T, Yamamura K, Magoshi Y, Kunimura K, Kamikaseda Y, Furue M, Fukui Y (2019) Selective role of neurokinin B in IL-31–induced itch response in mice. J Allergy Clin Immunol 144(4):1130-1133. doi: 10.1016/j.jaci.2019.06.031
Objective: To examine the physiological significance of neurokinin B in IL-31–induced itch sensation.
Summary: IL-31–induced scratching was unaffected by intrathecal injection of Nppb-SAP. In contrast,treatment with Bombesin-SAP reduced IL-31–induced scratching. Neurokinin B acts upstream of GRP to transmit IL-31–induced itch sensation.
Acton D, Ren X, DiCostanzo S, Dalet A, Bourane S, Bertocchi I, Eva C, Goulding M (2019) Spinal neuropeptide Y1 receptor-expressing neurons form an essential excitatory pathway for mechanical itch. Cell Reports 28(3):625-639.e6 . doi: 10.1016/j.celrep.2019.06.033
Objective: To determine the central pathway for mechanical itch.
Summary: NPY-Y1 signaling regulates the transmission of innocuous tactile information by establishing biologically relevant thresholds for touch discrimination and mechanical itch reflexes. Neither the evoked nor spontaneous scratching seen following activation of Y1Cre neurons was affected by ablation of the GRPR+ neurons. NK1R+ neuron ablation failed to modulate mechanically evoked itch.
Usage: P28 mice were given a single intrathecal (i.t.) injection of either Bombesin-SAP (400 ng in 5 mL 0.9% sterile saline) to ablate GRPR+ cells or SSP-SAP to ablate NK1r+ neurons (100 ng in 5 mL 0.9% sterile saline). Littermate controls received Blank-SAP (equal mass in 5 mL 0.9% sterile saline).
