targeted-toxins

LaPlante F (2013) Featured Article: Role of cholinergic neurons in the nucleus accumbens and their involvement in schizophrenic pathology. Targeting Trends 14(1)

Related Products: Anti-ChAT-SAP (Cat. #IT-42), Rabbit IgG-SAP (Cat. #IT-35)

Read the featured article in Targeting Trends.

See Also:

• Laplante F et al. Reduction in cholinergic interneuron density in the nucleus accumbens attenuates local extracellular dopamine release in response to stress or amphetamine. Synapse 67(1):21-29, 2013.

Kukkonen JP (2013) Physiology of the orexinergic/hypocretinergic system: a revisit in 2012. Am J Physiol Cell Physiol 304(1):C2-32 . doi: 10.1152/ajpcell.00227.2012

Summary: This review updates an original review from a decade ago on the subject of orexins. These neuropeptides have been shown to be involved in sleep, wakefulness, appetite, metabolism, stress response, reward/addiction, and analgesia. This broad spectrum of action affects many processes including neuronal excitation, synaptic plasticity, and cell death. The use of orexin-SAP (Cat. #IT-20) in some of this work is discussed.

Related Products: Orexin-B-SAP (Cat. #IT-20)

Anaclet C, Lin JS, Vetrivelan R, Krenzer M, Vong L, Fuller PM, Lu J (2012) Identification and characterization of a sleep-active cell group in the rostral medullary brainstem. J Neurosci 32(50):17970-17976. doi: 10.1523/JNEUROSCI.0620-12.2012

Summary: The authors attempt to locate and identify specific neuronal populations that promote sleep. One method utilized was 130-330 pg injections of orexin-SAP (Cat. #IT-20) into the parafacial zone. These results establish the parafacial zone as a delimited node of sleep-active neurons.

Related Products: Orexin-B-SAP (Cat. #IT-20)

Cusulin C, Monni E, Ahlenius H, Wood J, Brune J, Lindvall O, Kokaia Z (2012) Embryonic stem cell-derived neural stem cells fuse with microglia and mature neurons. Stem Cells 30:2657-2671. doi: 10.1002/stem.1227

Summary: The fusogenic role of microglia could be even more important after NSC transplantation into brains affected by neurodegenerative diseases associated with microglia activation.

Usage: Primary Cells and NS Cell Coculture. Seven to twelve days after plating primary cells, NS cells were plated on top (10,000 cells per cm2)  for 1–3 days. Rat primary cells were treated with 10 nM Mac-1-SAP or Mouse IgG-SAP during the 5 days prior to the coculture, and analyzed 3 days thereafter.

Related Products: Mac-1-SAP rat (Cat. #IT-33), Mouse IgG-SAP (Cat. #IT-18)

Kaminski KL, Watts AG (2012) Intact catecholamine inputs to the forebrain are required for appropriate regulation of corticotrophin-releasing hormone and vasopressin gene expression by corticosterone in the rat paraventricular nucleus. J Neuroendocrinol 24(12):1517-1526. doi: 10.1111/j.1365-2826.2012.02363.x

Summary: Corticosterone releasing hormone (CRH) neurons in the paraventricular nucleus of the hypothalamus (PVH) control release of adrenocorticotropic hormone and glucocorticoids. In order to determine the contribution of these neurons to CRH and vasopressin expression in the PVH the authors administered bilateral 42 ng injections of anti-DBH-SAP (Cat. #IT-03) into the PVH of both normal and adrenalectomized rats. Mouse IgG-SAP (Cat. #IT-18) was used as a control. The data demonstrate that under certain conditions CRH and vasopressin gene expression is modulated by interactions between corticosterone and catecholaminergic projections to the hypothalamus.

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

Mittelman-Smith MA, Williams H, Krajewski-Hall SJ, McMullen NT, Rance NE (2012) Role for kisspeptin/neurokinin B/dynorphin (KNDy) neurons in cutaneous vasodilatation and the estrogen modulation of body temperature. Proc Natl Acad Sci U S A 109(48):19846-19851. doi: 10.1073/pnas.1211517109

Summary: Menopause is marked by estrogen withdrawal, and also by hot flushes. Given the fact that hypothalamic levels of kisspeptin/neurokinin B/dynorphin (KNDy) neurons are significantly altered in menopause, the authors investigated whether these neurons are involved in the generation of flushes. Rats received bilateral injections of NK3-SAP (Cat. #IT-63) into the arcuate nucleus – a total of 40 ng. Blank-SAP (Cat. #IT-21) was used as control. The data indicate that KNDy neurons promote cutaneous vasodilation, and play a role in 17β-estradiol modulation of body temperature, supporting the hypothesis that these neurons could play a role in the generation of hot flushes.

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

Kerbler GM, Hamlin AS, Pannek K, Kurniawan ND, Keller MD, Rose SE, Coulson EJ (2013) Diffusion-weighted magnetic resonance imaging detection of basal forebrain cholinergic degeneration in a mouse model. Neuroimage 66C:133-141. doi: 10.1016/j.neuroimage.2012.10.075

Summary: The authors examined the effectiveness of diffusion MRI using diffusion tensor imaging (DTI) and probabilistic tractography in detecting cholinergic loss in a mouse model. Mice received bilateral 0.2-μg icv injections of mu p75-SAP (Cat. #IT-16). Rabbit IgG-SAP (Cat. #IT-35) was used as control. The animals were then examined using DTI. The data indicate that DTI is a valid technique for assessment of cholinergic loss in septo-hippocampal tracts as a result of Alzheimer’s disease.

Related Products: mu p75-SAP (Cat. #IT-16), Rabbit IgG-SAP (Cat. #IT-35)

Vetrivelan R, Fuller PM, Yokota S, Lu J, Saper CB (2012) Metabolic effects of chronic sleep restriction in rats. Sleep 35(11):1511-1520. doi: 10.5665/sleep.2200

Summary: In order to investigate whether there is a correlation between sleep and weight the authors administered 200 nl of a 0.1% solution of orexin-SAP (Cat. #IT-20) to the ventrolateral preoptic area of rats. Although the lesioned animals slept less than the controls, weight gain was slower than controls.

Related Products: Orexin-B-SAP (Cat. #IT-20)

Ljubojevic V, Botly L, De Rosa E (2012) Cholinergic contributions to learned attentional suppression in the rat with touchscreens. Neuroscience 2012 Abstracts 729.13. Society for Neuroscience, New Orleans, LA.

Summary: One of the tasks of the attentional system is to filter environmental input according to its behavioral relevance. The neuromodulator acetylcholine (ACh) is thought to play a role in this process because of its ability to boost the signal-to-noise ratio of incoming sensory information. Cholinergic innervation of the attentional system has been shown to be necessary for successful selection of behaviorally-relevant stimuli (signal). However, it is not yet clear if ACh also plays a part in the attentional suppression of behaviorally-irrelevant information (noise). Thus, we examined the effect of cortical cholinergic deafferentation on attentional suppression in rats. To measure attentional suppression, we used a rat analog of the learning-to-ignore (LI) task originally designed for human participants (Dixon et al., 2009). The paradigm consisted of three stages of training (Prime1, Prime2, Probe; 10 sessions per stage), each of which involved stages of visual simultaneous discriminations between two stimuli. In both Prime conditions, individuals learned to respond to target stimuli (A+ and then C+ respectively), while ignoring the same distractor stimulus (B-). During Probe, the previously ignored stimulus became the target (B+) and a novel stimulus (D-) was introduced as a distractor. Eighteen male Long-Evans rats were trained to perform the touchscreen-based LI task. Like the human data, a behavioral decrement (lower accuracy) was observed during the Probe phase of the LI task when compared to Prime 1 and 2, which suggests that the ignored distractor stimulus was suppressed during Prime. We hypothesized that administration of the ACh-specific immunotoxin, 192 IgG-saporin, into the nucleus basalis magnocellularis (NBM) would lead to better performance during Probe condition relative to controls. Accordingly, the rats were subjected to either cholinergic immunotoxic (SAP, N=10) or sham lesion surgery (SHAM, N=8). After 2 weeks of post-surgical recovery, the rats were tested on the LI task with a new stimulus set. The two groups performed comparably during Prime1 and 2, with both SAP and SHAM rats successfully learning the discriminations. As predicted, during Probe SAP rats exhibited significantly less behavioral decrement than controls. Histological analysis revealed that the lesion was chemically and anatomically specific to cholinergic cells in the NBM. This counterintuitive finding suggests that the improved performance during Probe, due to reduced ACh input to the neocortex, was due to inefficient attentional suppression of the behaviorally-irrelevant stimulus.

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

Ortiz-Barajas O, Ramos-Rodriguez J, Berrocoso E, Garcia Alloza M (2012) Limited effect of serotonergic denervation on beta-amyloid and cognitive impairment in APPswe/PS1dE9 mice. Neuroscience 2012 Abstracts 751.12. Society for Neuroscience, New Orleans, LA.

Summary: Alzheimer’s Disease (AD) is a neurodegenerative disease characterized by progressive cognitive and memory impairment. Amyloid-beta (Aβ) deposition, as senile plaques (SP), seems to play a key role in the development and progression of the illness. Moreover SP tend to accumulate in cortex and hippocampus, relevant areas in learning and memory. On the other hand neuronal loss is the pathological feature that best correlates with duration and severity of the illness and at present animal available animal models hardly reproduce the complexity of the disease. We have previously seen that selective cortical and hipocampal cholinergic denervation, using murine p-75 saporin, may worsen cognitive abilities in APPswe/PS1dE9 mice as well as increase SP deposition in denervated areas. In the present work we lesioned 7 months old APPswe/PS1dE9 mice with 1 µl of 5,7-dyhidroxytiptamine (0.16 µg/µl) injected in the raphe nucleus (RN). In order to guarantee selective removal of cortical and hipocampal serotonergic inervation, and protect noardernergic and dopaminergic neurons, animals were i.p. injected with desipramine and nomifensine before surgery. We observed a clear reduction of tryptophan hydroxilase staining in the RN. In the Morris water maze test we observed learning and memory impairment in APPswe/Ps1dE9 mice, without a synergistic effect of the serotonergic lesion. When we assessed SP deposition we did not observe a significant increase of SP in cortex or hipocampus 14 days after the lesion, as we observed after selective cholinergic denervation. Altogether our data suggest that cognitive impairment and induced SP depositioin observed after cholinergic denervation is not achieved when serotonergic system is affected, supporting a selective effect mediated by different neurotransmitter systems. Acknowledgements: MG-A: RYC-2008-02333, ISCIII-Subdirección General de Evaluación y Fomento de la Investigación (PS09/00969), Fundación Dr. Eugenio Rodriguez Pascual, Junta Andalucia Excelencia (CTS-7847).

Related Products: mu p75-SAP (Cat. #IT-16)