targeted-toxins

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)

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)

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)

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)

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)

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)

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)

Harasawa I, Johansen J, Fields H, Porreca F, Meng I (2016) Alterations in the rostral ventromedial medulla after the selective ablation of μ-opioid receptor expressing neurons. Pain 157:166-173. doi: 10.1097/j.pain.0000000000000344

Summary: The rostral ventromedial medulla (RVM) has both excitatory and inhibitory control over nociceptive neurons in the medullary dorsal horn and spinal cord. Previous work has demonstrated that elimination of mu-opioid receptor-expressing neurons in the RVM reduces stress and injury-induced behavioral hypersensitivity, but the effect of losing these cells on the descending inhibitory system has not been examined. The authors administered 1.2 pmol of Dermorphin-SAP (Cat. #IT-12) to each side of the RVM of rats. Saporin (Cat. #PR-01) was used as a control. Characterization of RVM neurons in lesioned animals showed a reduction in on- and off-cells, but no change in the number of neutral cells. These data indicate that mu-opioid receptor-expressing cells in the RVM are not needed for analgesia produced by activation of RVM neurons.

Related Products: Dermorphin-SAP / MOR-SAP (Cat. #IT-12), Saporin (Cat. #PR-01)