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Neuroteratology and animal modeling of brain disorders
Archer T, Kostrzewa RM (2016) Neuroteratology and animal modeling of brain disorders. Curr Top Behav Neurosci 29:1-40. doi: 10.1007/7854_2015_434
Summary: This work covers development and use of the neurotoxins that are most commonly used as neuroteratologic agents – producing permanent, lifelong destruction of specific groups of neurons. Saporin conjugates are discussed, in terms of animal models of human neurodegenerative, neuropsychiatric, and neurological conditions. In contrast to 192 IgG-SAP treatment of adult rats,which also destroys cerebellar Purkinje cells, perinatal 192 IgG-saporin spares Purkinje cells which have a lower expression of p75NGF
Related Products: 192-IgG-SAP (Cat. #IT-01)
Brain penetration, target engagement, and disposition of the blood-brain barrier-crossing bispecific antibody antagonist of metabotropic glutamate receptor type 1.
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)
Roles of isolectin B4-binding afferents in colorectal mechanical nociception.
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)
Participation of D-serine in the development and reproduction of the silkworm Bombyx mori.
Tanigawa M, Suzuki C, Niwano K, Kanekatsu R, Tanaka H, Horiike K, Hamase K, Nagata Y (2016) Participation of D-serine in the development and reproduction of the silkworm Bombyx mori. J Insect Physiol 87:20-29. doi: 10.1016/j.jinsphys.2016.01.006 PMID: 26828952
Summary: The silkworm Bombyx mori is known to contain high levels of free D-serine, an optical isomer of L-serine. In this work, the authors investigated the localization of D-serine in various organs of the silkworms in various stages of life in an effort to elucidate its role. They used an immunohistochemical approach to localize D-serine to the silkworm hemolymph, midgut, testes, ovaries, and fat bodies. They also used rabbit antibody against glutaraldehyde-conjugated D-alanine (Cat. #AB-T049) to examine the distribution of D-alanine throughout the silkworms. The authors treated silkworms with an inhibitor of serine racemase to reduce the conversion of L- to D-serine and on the basis of their results suggested the possible involvement of D-serine in ATP synthesis for metamorphosis and reproduction.
A non-inheritable maternal Cas9-based multiple-gene editing system in mice.
Sakurai T, Kamiyoshi A, Kawate H, Mori C, Watanabe S, Tanaka M, Uetake R, Sato M, Shindo T (2016) A non-inheritable maternal Cas9-based multiple-gene editing system in mice. Sci Rep 6:20011. doi: 10.1038/srep20011
Summary: In this work, the authors generated transgenic mice with systemic Cas9 overexpression (Cas9 mice) in order to simplify the procedure of generating genetically modified animals using the CRISPR/Cas9 system – only guide RNAs (gRNAs) would need to be administered to induce mutations at target loci. To test Cas9 mice for genome editing in vitro, the authors transiently transfected primary fibroblasts from Cas9 mice with Ggta1 gRNA (Ggta1 is responsible for synthesizing the cell-surface α-Gal epitope). They treated the fibroblasts with rIB4-SAP (Cat. #IT-10) and found that it killed Ggta1 +/+ and KO/+ cells, while biallelic Ggta1 KO cells survived as they did not synthesize the α-Gal epitope. This indicated that primary cells from the Cas9 transgenic mice have CRISPR/Cas9 genome editing capability with the administration of gRNA alone. The success of their experiments indicate that this method could potentially be used to generate other genetically modified animals.
Related Products: IB4-SAP (Cat. #IT-10)
An ID2-dependent mechanism for VHL inactivation in cancer.
Lee SB, Frattini V, Bansal M, Castano AM, Sherman D, Hutchinson K, Bruce JN, Califano A, Liu G, Cardozo T, Iavarone A, Lasorella A (2016) An ID2-dependent mechanism for VHL inactivation in cancer. Nature 529(7585):172-177. doi: 10.1038/nature16475 PMID: 26735018
Usage: Western blot
Related Products: Trans-4-Hydroxy-L-Proline Rabbit Polyclonal, Conjugated (Cat. #AB-T044)
The effect of nucleus basalis magnocellularis deep brain stimulation on memory function in a rat model of dementia.
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)
Reorganization of motor cortex by vagus nerve stimulation requires cholinergic innervation.
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)
Featured Article: Striatal patch compartment lesions reduce cocaine-induced repetitive behaviors
Horner KA, Murray R, Logan Merce MC (2016) Featured Article: Striatal patch compartment lesions reduce cocaine-induced repetitive behaviors. Targeting Trends 17(1)
Related Products: Dermorphin-SAP / MOR-SAP (Cat. #IT-12)
Read the featured article in Targeting Trends.
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Basal forebrain cholinergic deficits reduce glucose metabolism and function of cholinergic and gabaergic systems in the cingulate cortex.
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)