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Ablation of μ opioid receptor-expressing GABA neurons in rostromedial tegmental nucleus increases ethanol consumption and regulates ethanol-related behaviors.
Fu R, Chen X, Zuo W, Li J, Kang S, Zhou L, Siegel A, Bekker A, Ye J (2016) Ablation of μ opioid receptor-expressing GABA neurons in rostromedial tegmental nucleus increases ethanol consumption and regulates ethanol-related behaviors. Neuropharmacology 107:58-67. doi: 10.1016/j.neuropharm.2016.02.027
Summary: In this work the authors investigated cellular mechanisms underlying the aversive effects of alcohol that limit its intake. Previous work has linked synaptic inhibition of dopamine neurons in the ventral tegmental area to this aversion. Rats conditioned to ingest ethanol received bilateral injections totaling 3 pmol of Dermorphin-SAP (Cat. #IT-12) into the rostromedial tegemental nucleus (RTMg). Blank-SAP (Cat. #IT-21) was used as a control. Lesioned animals displayed significantly increased preference for, and intake of ethanol, while showing no change in the desire for sucrose. The results indicate that mu opioid expressing GABAergic neurons in the RTMg are highly involved in the regulation of ethanol consumption.
Related Products: Dermorphin-SAP / MOR-SAP (Cat. #IT-12), Blank-SAP (Cat. #IT-21)
The peptidergic control circuit for sighing.
Li P, Janczewski W, Yackle K, Kam K, Pagliardini S, Krasnow M, Feldman J (2016) The peptidergic control circuit for sighing. Nature 530:293-297. doi: 10.1038/nature16964
Summary: Sighs are often associated with relief or sadness, but rodents sigh spontaneously dozens of times per hour. There are physiological benefits to sighing, including enhancement of gas exchange and preservation of lung integrity. The authors identify a peptidergic sigh control circuit in the retrotrapezoid nucleus/parafacial respiratory group of the mouse brain that projects to the pre-Bötzinger complex. Mice received bilateral 6.2-ng injections of Bombesin-SAP (Cat. #IT-40) into the pre-Bötzinger complex. Blank-SAP (Cat. #IT-21) was used as control. Elimination of the bombesin receptor-expressing neurons or inhibition of neuromedin B receptor-expressing neurons suppressed sighing. Interfering with the activity of both receptors abolished sigh activity while leaving normal breathing intact. The data suggest that overlapping peptidergic pathways are the core of a sigh control circuit.
Related Products: Bombesin-SAP (Cat. #IT-40), Blank-SAP (Cat. #IT-21)
Lysophosphatidylcholine acyltransferase 1 protects against cytotoxicity induced by polyunsaturated fatty acids.
Akagi S, Kono N, Ariyama H, Shindou H, Shimizu T, Arai H (2016) Lysophosphatidylcholine acyltransferase 1 protects against cytotoxicity induced by polyunsaturated fatty acids. FASEB J 30:2027-2039. doi: 10.1096/fj.201500149 PMID: 26887439
Summary: Dietary consumption of polyunsaturated fatty acids can influence the degree of fatty acid unsaturation in membrane phospholipids, and consequently membrane-associated functions. Scientists set out to investigate how mammalian cells change their membrane lipid composition in response to loading with excess polyunsaturated fatty acids (PUFAs). Lipidomic analysis showed that PUFA treatment induces production of dipalmitoylphosphatidylcholine (DPPC). By suppressing phospholipid metabolism-related genes by RNA interference, they found that Lysophosphatidylcholine acyltransferase 1 (LPCAT1) was involved in DPPC production. To reveal the role of DPPC produced by PUFA treatment, HeLa cells were transfected with a siRNA against LPCAT1 to reduce its protein expression. The cells were lysed after treatment with a PUFA and subjected to western blot analysis using a 1:1000 dilution of Anti-SCD-1 (Cat. #AB-259) as the primary. SCD-1 desaturates the substrate of LPCAT1 for producing DPPC. PUFAs significantly reduced both the protein and mRNA expression of SCD-1. They showed that inhibiting DPPC production by LPCAT1 knockdown enhanced apoptosis, suggesting that DPPC produced via LPCAT1 protects against PUFA-induced cytotoxicity.
Related Products: SCD-1 Mouse Monoclonal (Cat. #AB-259)
Cholinergic deafferentation of the hippocampus causes non-temporally graded retrograde amnesia in an odor discrimination task.
Köppen J, Stuebing S, Sieg M, Blackwell A, Blankenship P, Cheatwood J, Wallace D (2016) Cholinergic deafferentation of the hippocampus causes non-temporally graded retrograde amnesia in an odor discrimination task. Behav Brain Res 299:97-104. doi: 10.1016/j.bbr.2015.11.021
Summary: The memory impairments experienced in neurodegenerative disorders such as Alzheimer’s disease have been well documented. One theory attributes these impairments to the loss of cholinergic basal forebrain neurons, a hallmark of Alzheimer’s disease. Some patients experience a retrograde amnesia, in which older memories are relatively stable and more recent memories are frequently lost. The temporal relationship of memories to disease onset has not been definitively established. In this work the authors administered either 150 ng or 200 ng of 192-IgG-SAP (Cat. #IT-01) into the medial septum of rats. Using a string-pulling task, a model for temporal learning was established. The results indicate that cholinergic projections originating in the medial septum are involved in long-term memory retrieval, and that loss of these neurons does not create a temporal type of amnesia.
Related Products: 192-IgG-SAP (Cat. #IT-01)
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)