targeted-toxins

Yao Y, Echeverry S, Shi X, Yang M, Yang Q, Wang G, Chambon J, Wu Y, Fu K, De Koninck Y, Zhang J (2016) Dynamics of spinal microglia repopulation following an acute depletion. Sci Rep 6:22839. doi: 10.1038/srep22839

Summary: This study confirms that similar to microglia in the brain, spinal microglia can repopulate rapidly following elimination, which is driven essentially by a self-renewal process. To deplete microglia in spinal cords, Mac-1-SAP (Cat. #IT-06) was injected i.t. (7 μl, 1.6  μg/μl) at the level of L4-L5 in mouse. The results support the concept that microglia repopulation, whether in the brain or in the spinal cord, is the consequence of onsite resident microglia proliferation. Newly generated microglia are fully functional and are able to respond to peripheral nerve injury and contribute to the development of neuropathic pain.

Related Products: Mac-1-SAP mouse/human (Cat. #IT-06)

Fei Y, Wang X, Chen S, Zhou Q, Zhang C, Li Y, Sun L, Zhang L (2016) Role of the RVM in descending pain regulation originating from the cerebrospinal fluid-contacting nucleus. Neurochem Res 41:1651-1661. doi: 10.1007/s11064-016-1880-6

Summary: The researchers investigated whether the CSF-contacting nucleus contributed to descending pain modulation in normal and neuropathic rats, and detected the 5-HT expression changes in both RVM and spinal dorsal cord. They also detected the possible anatomical and function correlation between the CSF-contacting nucleus and the RVM. Targeted ablation of the CSF-contacting nucleus was performed using CTB-SAP (Cat. #IT-14; 500 ng/3 μl), which was administered i.c.v. to the normal rats and rats 7 days before the CCI procedure. Based on the findings of the present study, they believe that the CSF-contacting nucleus may act as a component of descending pain regulation system. RVM, which acts as an important brain nucleus, is involved in the relay of nociceptive information between the CSF-contacting nucleus and spinal cord. Moreover, RVM 5-HT system plays a critical role in descending pain inhibition originating from the CSF-contacting nucleus.

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

Gritsch S, Bali K, Kuner R, Vardeh D (2016) Functional characterization of a mouse model for central post-stroke pain. Mol Pain 12:1744806916629049. doi: 10.1177/1744806916629049

Summary: While clinical evidence has pointed toward central pain pathway dysfunction in central post-stroke pain (CPSP), the underlying mechanisms have not been defined. In this work the authors created a mouse model of CPSP through lesions of the thalamic ventral posterolateral nucleus. In order to examine the role of neurokinin-1 receptor-expressing (NK1R) neurons in lamina I/III of the spinal cord in the development and maintenance of CPSP the authors administered 1 μmol intrathecal injections of SSP-SAP (Cat. #IT-11). Saporin (Cat. #PR-01) was used as a control. While the NK1R+ neurons in the spinal cord were not involved in establishing CPSP, the data indicate that sensory changes in the mice are comparable to those observed in human patients with CPSP.

Related Products: SSP-SAP (Cat. #IT-11), Saporin (Cat. #PR-01)

Wang L, Conner J, Nagahara A, Tuszynski M (2016) Rehabilitation drives enhancement of neuronal structure in functionally relevant neuronal subsets. Proc Natl Acad Sci U S A 113:2750-2755. doi: 10.1073/pnas.1514682113

Summary: Rehabilitation is often prescribed after brain injury, but the basis for how training can influence brain plasticity and recovery is unclear. In this study, the authors show that intense rehabilitation training after focal brain injury drives significant structural changes in brain cells located adjacent to the injury. Importantly, a key brain modulatory system, the basal forebrain cholinergic system, is required for enabling rehabilitation to impact brain structure. Rats underwent cholinergic ablations by injecting 192-IgG-Saporin (Cat. #IT-01) into the nucleus basalis (0.2-0.25 mcl of 0.375 mg/ml solution in artificial CSF). Damage to the cholinergic system, which can occur naturally during aging, completely blocks brain plasticity mediated by rehabilitation and significantly attenuates functional recovery. These results provide new insights into how rehabilitation may promote recovery and suggest that brain cholinergic systems may be a possible therapeutic target for influencing recovery.

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

Vazquez-DeRose J, Schwartz M, Nguyen A, Warrier D, Gulati S, Mathew T, Neylan T, Kilduff T (2016) Hypocretin/orexin antagonism enhances sleep-related adenosine and GABA neurotransmission in rat basal forebrain. Brain Struct Funct 221:923-940. doi: 10.1007/s00429-014-0946-y

Summary: The basal forebrain (BF) is one of the regions receiving excitatory input from orexin neurons. The authors investigated the hypothesis that orexin antagonists induce sleep at least in part by interfering with the facilitation of BF neurons. Rats received bilateral 500-ng injections of 192-IgG-SAP (Cat. #IT-01) into the BF. Lesioned animals displayed no abnormal responses to a benzodiazepine agonist or vehicle. An orexin antagonist, however, was less effective than the control at inducing sleep in lesioned rats.

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

Mittelman-Smith M, Krajewski-Hall S, McMullen N, Rance N (2016) Ablation of KNDy neurons results in hypogonadotropic hypogonadism and amplifies the steroid-induced LH surge in female rats. Endocrinology 157:2015-2027. doi: 10.1210/en.2015-1740

Summary: KNDy neurons are a subpopulation of neurons in the infundibular nucleus that coexpress estrogen receptor α, kisspeptin, and neurokinin B (NKB) mRNA. Previous work indicated that altered signaling from KNDy neurons may play a role in the low levels of circulating sex steroids found in hypogonadotropic hypogonadism. Rats received bilateral 10-ng injections of NK3-SAP (Cat. #IT-63) dorsal to the arcuate nucleus. Blank-SAP (Cat. #IT-21) was used as control. In animals with intact ovaries the NK3-SAP lesion resulted in hypogonadotropic hypogonadism. In contrast, the LH surge in lesioned ovariectomized rats was 3-fold higher, demonstrating that KNDy neurons are integral for the control of serum LH levels, estrous cyclicity, and may also have some control over the magnitude of the LH surge.

Related Products: NKB-SAP (Cat. #IT-63), Blank-SAP (Cat. #IT-21)

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)