2021 Targeting Trends Review

Borkowski L, Nichols N (2021) Utilization of pectoralis minor accessory inspiratory muscles in a rodent model of respiratory motor neuron loss. FASEB J 35(S1) Experimental Biology 2021 Meeting Abstracts. doi: 10.1096/fasebj.2021.35.S1.01843 PMID: 0

Objective: To develop a model of selective respiratory motor neuron death to study how breathing is impacted and advance targeted therapeutic interventions.

Summary: Prior to ventilatory failure, patients can maintain breathing potentially via recruitment of accessory inspiratory muscles (e.g., pectoralis minor). The data suggest that the pectoralis minor muscles have an independent motor pool that can become recruited to assist in maintaining eupnea (normal respiration).

Usage: Adult male rats received bilateral CTB-SAP or control (CTB unconjugated to SAP) intrapleurally.

Related Products: CTB-SAP (Cat. #IT-14)

Aikins A, Little J, Cunningham, J (2021) Role of A1/A2 neurons in the dysregulation of vasopressin release and dilutional hyponatremia in liver disease. FASEB J 35(1) Experimental Biology 2021 Meeting Abstracts. doi: 10.1096/fasebj.2021.35.S1.04975 PMID: 0

Summary: Experiments suggest that A1/A2 neurons could be involved in the increased plasma AVP seen in male BDL rats as well as the decreased plasma osmolality.

Usage: Selective lesioning of the supraoptic nucleus (SON)-projecting A1/A2 norepinephrine neurons was achieved using anti-DBH-SAP.

Related Products: Anti-DBH-SAP (Cat. #IT-03)

Ku SK, Lim JM, Cho HR, Bashir KMI, Kim YS, Choi JS (2021) Tart cherry (fruit of prunus cerasus) concentrated powder (tccp) ameliorates glucocorticoid-induced muscular atrophy in mice. Medicina (Kaunas) 57(5):485. doi: 10.3390/medicina57050485 PMID: 34066110

Summary: Tart cherries have shown memory impairment lowering properties.

Related Products: mu p75-SAP (Cat. #IT-16)

See Also:

• Matchynski JJ et al. Combinatorial Treatment of Tart Cherry Extract and Essential Fatty Acids Reduces Cognitive Impairments and Inflammation in the mu-p75 Saporin-Induced Mouse Model of Alzheimer’s Disease. J Med Food 16(4):288-295, 2013.

Kawanabe R, Yoshihara K, Hatada I, Tsuda M (2021) Activation of spinal dorsal horn astrocytes by noxious stimuli involves descending noradrenergic signaling. Mol Brain 14(1):79. doi: 10.1186/s13041-021-00788-5

Summary: Astrocytes are critical regulators of neuronal function in the central nervous system (CNS). Astrocytes in the spinal dorsal horn (SDH) increase intracellular Ca2+ levels following intraplantar injection of the noxious irritant, formalin, however the underlying mechanisms remain unknown. The authors investigated these mechanisms by focusing on the role of descending noradrenergic (NAergic). Activation of α1A-adrenaline receptors via descending LC-NAergic signals may be a common mechanism underlying astrocytic Ca2+ responses in the SDH evoked by noxious stimuli, including chemical irritants

Usage: Intrathecal treatment with Anti-DBH-SAP, which kills SDH-projecting NAergic neurons, attenuates formalin pain (5.0 µg/20 µl; Martin et al., 1999)

See: Martin WJ et al. Differential effects of neurotoxic destruction of descending noradrenergic pathways on acute and persistent nociceptive processing. Pain 80:57-65, 1999.

Related Products: Anti-DBH-SAP (Cat. #IT-03)

Kim HN, Kim JY (2021) A systematic review of oropharyngeal dysphagia models in rodents. Int J Environ Res Public Health 18(9):4987. doi: 10.3390/ijerph18094987

Objective: To organize the rodent models of oropharyngeal dysphagia reported to date.

Summary: Applying and analyzing the treatment in rodent models of dysphagia induced from various causes is an essential process to develop symptom-specific treatments. The results of this study provide fundamental and important data for selecting appropriate animal models to study dysphagia.

Usage: CTB-SAP treated rats exhibited targeted hypoglossal motor neuron death; decreased hypoglossal motor output; and swallowing and lick deficits.

Related Products: CTB-SAP (Cat. #IT-14)

da Costa C, Soares JI, Lukoyanov NV (2021) Forebrain cholinergic plasticity in rats with chronic epilepsy induced by status epilepticus. . 14th U.PORTO Young Researchers Meeting

Summary: This poster had the following aims: 1) Evaluate the GABAergic population in the MS/DB in a chronic epilepsy model of kainic acid (KA)-treated rats. 2) Assess the GABAergic and cholinergic interconnectivity in the MS/DB in a chronic epilepsy model of kainic acid (KA)-treated rats. Results showed that outcomes were improved in rats receiving 192-IgG-SAP treatment as compared to Sham. Mortality: Sham – 50%; SAP – 0%.Recurrent motor seizures: Sham – 83%; SAP – 40%. Recurrent motor + EEG seizures: Sham – 100%; SAP – 50%.

Usage: 192-IgG-SAP was used to produce a moderate, but significant loss of septohippocampal cholinergic cells and to suppress their plasticity.

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

Ming X, Prasad N, Thulasi V, Elkins K, Shivamurthy VKN (2021) Possible contribution of cerebellar disinhibition in epilepsy. Epilepsy Behav 118:107944. doi: 10.1016/j.yebeh.2021.107944

Summary: The authors hypothesize that loss of inhibition from the cerebellum can lead to cortical activation and seizures. An animal study showed microinjection of SSP-SAP produced a selective ablation of hippocampal inhibitory interneurons in vivo and a highly focal disinhibition. These results also demonstrate that the ‘‘epileptic” pathophysiology produced by experimental status epilepticus or head trauma can be replicated by focal interneuron loss, without involving principal cell loss and other interpretive confounds inherent in the use of global neurologic injury models.

Related Products: SSP-SAP (Cat. #IT-11)

See Also:

• Martin JL et al. Focal inhibitory interneuron loss and principal cell hyperexcitability in the rat hippocampus after microinjection of a neurotoxic conjugate of saporin and a peptidase-resistant analog of substance P. J Comp Neurol 436:127-152, 2001.
• Chun E et al. Targeted hippocampal GABA neuron ablation by stable substance P-saporin causes hippocampal sclerosis and chronic epilepsy in rats. Epilepsia 60(5):e52-e57, 2019.

Gonzalez EA, Leitão SAT, Dos Santos Soares D, Tavares AMV, Giugliani R, Baldo G, Matte U (2021) Cardiac pathology in Mucopolysaccharidosis I mice: Losartan modifies ERK1/2 activation during cardiac remodeling. J Inherit Metab Dis 44(3):740-750. doi: 10.1002/jimd.12327 PMID: 33145772

Objective: To investigate whether the pathways influenced by losartan and propranolol may modulate the cardiac remodeling process in MPS I mice.

Summary: Losartan and propranolol restore the heart function and could be used to ameliorate the cardiac disease in MPS I.

Usage: Western Blot 1:400

Related Products: Angiotensin II receptor (AT-1R) Rabbit Polyclonal, affinity-purified (Cat. #AB-N27AP)

Madrid LI, Jimenez-Martin J, Coulson EJ, Jhaveri DJ (2021) Cholinergic regulation of adult hippocampal neurogenesis and hippocampus-dependent functions. Int J Biochem Cell Biol 134:105969. doi: 10.1016/j.biocel.2021.105969

Summary: In this review, the authors appraise the evidence linking the contribution of cholinergic signalling to the regulation of adult hippocampal neurogenesis and hippocampus-dependent functions.

Usage: A hallmark feature of all basal forebrain cholinergic neurons is the expression of high levels of the p75 neurotrophin receptor which can be precisely targeted using 192-IgG-SAP. Administration of 192-IgG-SAP (icv, 2.5 µg, Mohapel et al., 2005) resulted in significant impairment in adult hippocampal neurogenesis in rats. In contrast, a study which lesioned MS cholinergic neurons in mice reported no effect on baseline proliferation in the hippocampus. Mice received 3.6 µg of mu p75-SAP into each lateral ventricle (Ho et al., 2009). Although the number of surviving neurons was similar in both lesioned and control animals, most of the progenitor cells in the lesioned animals could not survive without cholinergic input.

Related Products: 192-IgG-SAP (Cat. #IT-01), mu p75-SAP (Cat. #IT-16)

See Also:

• Mohapel P et al. Forebrain acetylcholine regulates adult hippocampal neurogenesis and learning. Neurobiol Aging 26:939-946, 2005.
• Ho NF et al. Effect of voluntary running on adult hippocampal neurogenesis in cholinergic lesioned mice. BMC Neurosci 10:57, 2009.

Penna S, Villa A, Capo V (2021) Autosomal recessive osteopetrosis: mechanisms and treatments. Dis Model Mech 14(5):dmm048940. doi: 10.1242/dmm.048940

Summary: Autosomal recessive osteopetrosis (ARO) is a severe inherited bone disease characterized by defective osteoclast resorption or differentiation. Novel therapeutic approaches are needed for ARO patients. The authors review preclinical and proof-of-concept studies, such as gene therapy, systematic administration of deficient protein, in utero Hematopoietic stem cell transplantation (HSCT) and gene editing.

Usage: Efficacy in HSCT conditioning was demonstrated with CD45.2-SAP (biotinylated Anti-CD45 mixed with Streptavidin-ZAP). In mice, CD45.2–SAP preserved normal bone marrow architecture compared to total body irradiation, which instead reduced vascular integrity and bone marrow cellularity. Mice conditioned with CD45.2–SAP rapidly recovered their peripheral myeloid cells and had a survival advantage when exposed to infections (3 mg/kg iv; Palchaudhuri et al.). Additionally, conditioning with CD45.2–SAP resulted in significant chimerism after transplantation, even in a pathological mouse model (3 mg/kg iv; Castiello et al.).

Related Products: Streptavidin-ZAP (Cat. #IT-27)

See Also:

• Palchaudhuri R et al. Non-genotoxic conditioning for hematopoietic stem cell transplantation using a hematopoietic-cell-specific internalizing immunotoxin. Nat Biotechnol 34:738-745, 2016.
• Castiello MC et al. Efficacy and safety of anti-CD45-saporin as conditioning agent for RAG deficiency. J Allergy Clin Immunol 147(1):309-320.e6, 2021.