tt2016

Webster C, Caram-Salas N, Haqqani A, Thom G, Brown L, Rennie K, Yogi A, Costain W, Brunette E, Stanimirovic D (2016) Brain penetration, target engagement, and disposition of the blood-brain barrier-crossing bispecific antibody antagonist of metabotropic glutamate receptor type 1. FASEB J 30:1927-1940. doi: 10.1096/fj.201500078 PMID: 26839377

Summary: To generate a BBB-transmigrating antibody that could be reformatted to full IgG, scientists started with the BBB-crossing llama single domain antibody FC5. Standard phage display protocols were used to isolate single-chain variable fragments (scFv) from the FC5-scFv library. 6His Mouse Monoclonal antibody (Cat. #AB-213) was used to assess cell binding of scFvs of FC5 using fluorescence microvolume assay technology. An scFv that competed with FC5 binding was selected for further testing. An antibody antagonist of the metabotropic glutamate receptor-1 was fused with this scFv antibody fragment (BBB-mGluR1) and tested in an in vitro BBB model. The resulting bispecific antibody retained selective mGluR1 binding and saw a 20-fold enhanced rate of transcytosis across the BBB compared to fusion with control antibody fragment. Intravenous injection of BBB-mGluR1 had analgesic properties in a rat model of persistent inflammatory pain.

Related Products: 6His Mouse Monoclonal (Cat. #AB-213)

La J, Feng B, Kaji K, Schwartz E, Gebhart G (2016) Roles of isolectin B4-binding afferents in colorectal mechanical nociception. Pain 157:348-354. doi: 10.1097/j.pain.0000000000000380

Summary: Primary afferent neurons are often classified as peptidergic or non-peptidergic. One characteristic of the non-peptidergic neurons is that they bind isolectin-B4. In the spinal cord these neurons terminate mainly in inner lamina II. Non-peptidergic neurons in the spinal cord have been found to be involved in various aspects of pain response. In this work the authors examined the role of non-peptidergic neurons in the viscerosensory system. Rats received 1.5 μg of intrathecal recombinant IB4-SAP (Cat. #IT-10) between the L5 and L6 vertebrae. Saporin (Cat. #PR-01) was used as a control. While IHC demonstrated that a majority of viscerosensory L6 colon DRG neurons are IB4+, they do not play a significant role in colorectal mechano-nociception.

Related Products: IB4-SAP (Cat. #IT-10), Saporin (Cat. #PR-01)

Lee J, Jeong D, Lee J, Chang W, Chang J (2016) The effect of nucleus basalis magnocellularis deep brain stimulation on memory function in a rat model of dementia. BMC Neurol 16:6. doi: 10.1186/s12883-016-0529-z

Objective: Deep brain stimulation (DBS) is the application of electrical impulses to specific parts of the brain for treating disorders such as Parkinson’s disease, chronic pain, and obsessive-compulsive disorder. This study investigated whether stimulation of brain structures associated with memory can enhance cognitive function.

Summary: Results indicate that DBS has beneficial effects on consolidation and retrieval of visuospatial memory.

Usage: The authors lesioned the basal forebrain of rats through bilateral injections totaling 5 μg of 192-IgG-SAP into the lateral ventricle. Animals then received DBS to the nucleus basalis magnocellularis and were tested in a Morris water maze task.

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

Hulsey D, Hays S, Khodaparast N, Ruiz A, Das P, Rennaker R, Kilgard M (2016) Reorganization of motor cortex by vagus nerve stimulation requires cholinergic innervation. Brain Stimul 9:174-181. doi: 10.1016/j.brs.2015.12.007

Summary: Recent work has suggested that vagus nerve stimulation (VNS) can enhance neuroplasticity, and coupled with other training can drive motor cortex reorganization. These findings highlight the potential of VNS to support recovery from neurological disease. Pretrained rats received bilateral injections totaling 3.75 μg of 192-IgG-SAP (Cat. #IT-01) into the nucleus basalis (NB). Mouse-IgG-SAP (Cat. #IT-18) was used as control. Control animals displayed a substantial increase in proximal limb representation, lesion of the NB prevented this increase. Motor performance was similar between lesion and control groups, indicating that the difference in representation was not due to altered limb function.

Related Products: 192-IgG-SAP (Cat. #IT-01), Mouse IgG-SAP (Cat. #IT-18)

Jeong D, Oh J, Lee J, Lee J, Cho Z, Chang J, Chang W (2016) Basal forebrain cholinergic deficits reduce glucose metabolism and function of cholinergic and gabaergic systems in the cingulate cortex. Yonsei Med J 57:165-172. doi: 10.3349/ymj.2016.57.1.165

Summary: A common result of cholinergic neuron loss in the hippocampus and cortical regions due to Alzheimer’s disease is a reduction in glucose metabolism. The authors examine the interaction between the cell loss and metabolic changes. Rats received 5-μg bilateral cortical injections of 192-IgG-SAP (Cat. #IT-01), were subject to water maze testing, and analyzed by 18F-2-fluoro-2-deoxyglucose positron emission tomography. Lesioned animals displayed decreased learning performance and reduced metabolic activity in the cingulate cortex.

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

Gulino R (2016) Neuroplasticity and repair in rodent neurotoxic models of spinal motoneuron disease. Neural Plast 2016:2769735. doi: 10.1155/2016/2769735

Summary: TDP-43 (Transactive response DNA-binding protein) is a highly conserved nuclear protein that binds both DNA and RNA. It has been found in cytoplasmic protein aggregates of patients with conditions such as amyotrophic lateral sclerosis and Alzheimer’s disease. In this work the authors examine the role of TDP-43 in spinal cord plasticity. Mice received bilateral 3-μg injections of CTB-SAP (Cat. #IT-14) into the lateral and medial gastrocnemius muscles. The results indicate that motor performance is dependent on expression of synapsin-I, which in turn may be dependent on TDP-43.

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

Petrosini L, De Bartolo P, Cutuli D, Gelfo F (2016) Perinatal 192 IgG-saporin as neuroteratogen. Curr Top Behav Neurosci 29:111-123. doi: 10.1007/7854_2015_418

Summary: The authors discuss the effects of perinatal administration of 192-IgG-SAP (Cat. #IT-01) and areas of research that have been investigated through the use of these lesions. The chapter covers a description of 192-IgG-SAP, lesioning methods, and outlines the short- and long-term biochemical, structural, behavioral, and cognitive effects of 192-IgG-SAP administration.

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

Chen Y, Pan C, Xuan A, Xu L, Bao G, Liu F, Fang J, Long D (2015) Treatment efficacy of NGF nanoparticles combining neural stem cell transplantation on Alzheimer’s Disease model rats. Med Sci Monit 21:3608-3615. doi: 10.12659/msm.894567

Summary: NSC (neural stem cell) transplants into animals have been shown to compensate for the loss of cholinergic cells in the basal forebrain, a hallmark of Alzheimer’s disease. One hurdle to overcome is the actuation of NSC differentiation into the specific replacement cells needed. NGF has been shown to induce this differentiation, but it has a very short half-life and does not permeate tissue very effectively. In this work the authors administered 5 mcl of icv 192-IgG-SAP (Cat. #IT-01) to rats, followed by a graft of NCSs in the presence of NGF nanoparticles with a polymer coating. Rats receiving both NCSs and NGF nanoparticles showed significantly improved memory and learning functions as compared to control animals.

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

Arora V, Morado-Urbina C, Aschenbrenner C, Hayashida K, Wang F, Martin T, Eisenach J, Peters C (2016) Disruption of spinal noradrenergic activation delays recovery of acute incision-induced hypersensitivity and increases spinal glial activation in the rat. J Pain 17:190-202. doi: 10.1016/j.jpain.2015.10.009

Summary: A significant percentage of patients who undergo surgery experience prolonged clinically impactful pain, reducing the quality of life and physical function. Disruption of the descending noradrenergic input has been hypothesized to be important to the generation of this type of pain state. Using an acute incision model, the authors administered 5 μg ofAnti-DBH-SAP (Cat. #IT-03) to the L5-L6 interspace of rats. Mouse IgG-SAP (Cat. #IT-18) was used as a control. Lesioned animals demonstrated a significant increase in mechanical hypersensitivity, and a smaller increase in thermal hypersensitivity. This and other results suggest that spinally projecting noradrenergic pathways are necessary for normal recovery from surgical incision, and possibly other types of pain.

Related Products: Anti-DBH-SAP (Cat. #IT-03), Mouse IgG-SAP (Cat. #IT-18)

Aicher S, Hermes S, Hegarty D (2015) Denervation of the lacrimal gland leads to corneal hypoalgesia in a novel rat model of aqueous dry eye disease. Invest Ophthalmol Vis Sci 56:6981-6989. doi: 10.1167/iovs.15-17497

Summary: One result of functional disruption of the tear gland is dry eye disease (DED), which represents a group of disorders rather than a singular one. DED manifests itself in altered responses to noxious corneal stimulation, but many of these patients do not actually have dry eyes or tear gland dysfunction. In order to investigate what circuits are involved in DED the authors created two models, one of which used the ablation of p75 receptor-expressing neurons innervating the extraorbital lacrimal gland. Rats received 2.5 μg of 192-IgG-SAP (Cat. #IT-01) directly into the left extraorbital lacrimal gland. Tear production in the lesioned animals was normal, and responses to noxious cold stimuli were impaired. This accompanied by unchanged fiber density indicates that the nociceptive signaling was affected on a molecular level.

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