targeted-toxins

Sivasathiaseelan H, Nunan R, Zaben M, Shtaya A, Gray WP (2009) The role of microglia and neuropeptides in regulating hippocampal neurogenesis. Neuroscience 2009 Abstracts 31.26/B52. Society for Neuroscience, Chicago, IL.

Summary: Adult mammalian neurogenesis is evident in the hippocampal dentate gyrus where it plays a role in learning and memory and is implicated in the pathophysiology of several brain disorders. Microglia, the innate immune cells of the brain, have recently emerged as an important component of the neurogenic niche, however their role in the regulation of neurogenesis under physiological and pathophysiological conditions is a matter of debate. The aim of this study is to investigate the effect of microglia on hippocampal neurogenesis and to look at how vasoactive intestinal peptide (VIP), a potent immunomodulatory neuropeptide found in dentate gyrus interneurons, modulates the effects microglia have on neurogenesis. In this study, we have investigated the effect of microglial depletion (using MAC-SAP), microglial co-culture and addition of microglia-conditioned-medium on primary hippocampal cell cultures derived from post-natal rats. We have also looked at how pre-treatment of microglia with VIP alters their effect on hippocampal cultures. Bromodeoxyuridine was used as a marker of cell proliferation. Quantification of cell death was achieved using the nuclear stain 4′,6-diamidino-2-phenylindole and Propidium Iodide. Immunohistochemistry was used to phenotype cells for nestin, GFAP and Tuj1. We have shown that microglial depletion results in a reduction in the numbers of nestin, GFAP and Tuj1 expressing cells. This reduction has been shown to be attributable to a decrease in cell survival and proliferation. Conversely, co-culture of microglia with hippocampal neurons or addition of their conditioned medium results in increased cell survival and proliferation. Pre-treatment of microglia with VIP was shown to increase both their proliferative and trophic effect on hippocampal cultures. In conclusion, this study demonstrates that microglia induce proliferative and trophic effects on neural stem cells and immature neurons through the release of soluble factors. Furthermore, we provide evidence that VIP regulates the release of these soluble factors, thus identifying a novel neuro-immuno-neurogenic link.

Related Products: Mac-1-SAP rat (Cat. #IT-33)

Dinh TT, Huston NJ, Ritter S (2009) Caudal hindbrain catecholaminergic projection to the ventrolateral bed nucleus of the stria terminalis (vlBNST): Assessment of role in glucoprivic and CCK feeding responses and corticosterone secretion. Neuroscience 2009 Abstracts 87.16/CC80. Society for Neuroscience, Chicago, IL.

Summary: Catecholamine neurons in the caudal hindbrain provide a significant innervation of the vlBNST and some of these neurons co-innervate the paraventricular nucleus of the hypothalamus (PVH). We previously found that PVH injections of the retrogradely-transported immunotoxin, anti-dopamine beta hydroxylase (DBH) saporin (anti-DBH-sap), profoundly reduced feeding and corticosterone responses to glucoprivation, but did not alter CCK-induced satiety, which has been linked to catecholamine neurons in the A2 cell group. In this experiment, we examined the origin of the vlBNST/PVH catecholamine projection and assessed its role in responses to glucoprivation and CCK. Retrograde tracing from vlBNST and PVH revealed dually-projecting DBH-ir (norepinephrine or epinephrine) neurons primarily in A2, A1 and caudal C1, with a few cells also present in C2. Dually-projecting PNMT-ir (epinephrine) were also present in C1 and in small numbers in C2. Overall, the relative numbers of DBH- and PMNT-ir neurons with projections to both vlBNST and PVH and the locations of these triply-labeled neurons indicate that the dually-projecting neurons are predominantly noradrenergic. Injections of anti-DBH-sap into the vlBNST produced cell losses in the hindbrain that were anatomically consistent in distribution and number with the tracing results. This immunotoxin caused a loss of DBH neurons in the dorsal hindbrain that was concentrated in the A2 cell group (14.6 – 13.68 mm caudal to bregma), where a maximum of 50% of DBH neurons were lesioned: 50% loss at 14.6 mm caudal to bregma, 25% at 13.24 mm and 0% at 11.96 mm. In ventral hindbrain, loss of DBH cell bodies was predominantly in the A1 cell group (14.6 – 12.8 mm caudal to bregma), where a maximum of 60% of DBH-ir neurons were lesioned: 60% loss at 14.6 and 13.68 mm, 22% at 13.24 and and 0% at 12.8 mm. In the dorsal hindbrain nearly all cells retrogradely labeled from the vlBNST were ipsilateral and DBH-ir. In ventral hindbrain there was a significant contralateral projection to vlBNST that was not DBH-ir. Anti-DBH-sap lesions did not impair the feeding, blood glucose or corticosterone responses to 2-deoxy-D-glucose (250 mg/kg) and did not impair the suppression of feeding by CCK-8 (4 ug/kg), indicating that the catecholamine projection to the vlBNST, including the dually-projecting neurons that innervate both the vlBNST and the PVH, is not required for these responses.

Related Products: Anti-DBH-SAP (Cat. #IT-03)

Chen ZF, Sun YG, Zhao ZQ, Meng XL, Yin J, Liu XY (2009) Featured Article: Ablation of GRPR+ neurons in the spinal cord by bombesin-saporin knocks out itch sensation in mice without affecting pain circuit. Targeting Trends 10(4)

Related Products: Bombesin-SAP (Cat. #IT-40), Blank-SAP (Cat. #IT-21)

Read the featured article in Targeting Trends.

See Also:

• Sun YG et al. Cellular basis of itch sensation. Science 325:1531-1534, 2009.

Jinks SL, Carstens E, Antognini JF (2009) Nitrous oxide-induced analgesia does not influence nitrous oxide’s immobilizing requirements. Anesth Analg 109:1111-1116. doi: 10.1213/ANE.0b013e3181b5a2a7

Summary: Noradrenergic neurons in the locus coeruleus (LC) are involved with the analgesic action of nitrous oxide (N2O). In order to examine whether these neurons are also involved with the immobilizing effects of N2O, rats received 4 µg intracerebroventricular injections of anti-DBH-SAP (Cat. #IT-03). Mouse IgG-SAP (Cat. #IT-18) was used as a control. Lesioned animals did not experience the analgesic effects of N2O, but the immobilizing effects were still present. The data demonstrate that the immobilizing mechanism of N2O is independent from its analgesic effects.

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

Lawhorn C, Smith DM, Brown LL (2009) Partial ablation of mu-opioid receptor rich striosomes produces deficits on a motor-skill learning task. Neuroscience 163(1):109-119. doi: 10.1016/j.neuroscience.2009.05.021

Summary: The functional role of basal ganglia striosomes is not well understood. In order to examine these cells in the context of motor behavior the authors injected 8.5 ng of dermorphin-SAP (Cat. #IT-12) into several areas of the striatum of mice (saporin, Cat. #PR-01, was used as a control). The animals were then evaluated in complex motor tasks involving the use of striatal circuitry. Animals receiving dermorphin-SAP showed deficits in specific motor tasks corresponding to the extent of the lesion.

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

Montero M, Gonzalez B, Zimmer J (2009) Immunotoxic depletion of microglia in mouse hippocampal slice cultures enhances ischemia-like neurodegeneration. Brain Res 1291:140-152. doi: 10.1016/j.brainres.2009.06.097

Summary: Data has shown microglia to be both neuroprotective and neurodegenerative in cerebral ischemia. This study presents a method for removing microglia from hippocampal slice cultures. Hippocampal slices from mouse were incubated with 13 nM Mac-1-SAP (Cat. #IT-06) for 3 to 7 days. The slices were then exposed to oxygen-glucose deprivation. Those cultures lacking microglia displayed significantly higher degeneration of CA1 pyramidal cells, indicating a neuroprotective role for microglia in this model.

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

Read the featured article in Targeting Trends.

Ingham ES, Gunhan E, Fuller PM, Fuller CA (2009) Immunotoxin-induced ablation of melanopsin retinal ganglion cells in a non-murine mammalian model. J Comp Neurol 516:125-140. doi: 10.1002/cne.22103

Related Products: Melanopsin-SAP (Cat. #IT-44)

Dashniani M, Burjanadze M, Beselia G, Maglakelidze G, Naneishvili T (2009) Spatial memory following selective cholinergic lesion of the nucleus basalis magnocellularis. Georgian Med News 174:77-81.

Summary: This study investigated the role of cholinergic nucleus basalis magnocellularis (NBM) cells in learning and memory. Rats received bilateral 200 ng injections of 192 IgG-SAP (Cat. IT-01) into the NBM. Mouse IgG-SAP (Cat. #IT-18) was used as a control. The results indicate that the NBM is important in accurate spatial learning and the processing of information about the spatial environment. Deficits in rats with the cholinergic lesion may be due to lowered attentional function.

Related Products: 192-IgG-SAP (Cat. #IT-01), Mouse IgG-SAP (Cat. #IT-18)

Conner JM, Franks KM, Titterness AK, Russell K, Merrill DA, Christie BR, Sejnowski TJ, Tuszynski MH (2009) NGF is essential for hippocampal plasticity and learning. J Neurosci 29:10883-10889. doi: 10.1523/JNEUROSCI.2594-09.2009

Summary: This work aimed to define NGF modulation of plasticity and function in adults. Rats received 50 ng injections of 192-IgG-SAP (Cat. #IT-01) into the medial septum. Lesioned animals exhibited impaired retention of spatial memory and significantly reduced hippocampal long term potentiation. These results indicate that NGF modulates neuronal plasticity and behavior by exerting effects on cholinergic projections to hippocampal and cortical targets.

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

Zhu J, Xu W, Wang J, Ali SF, Angulo JA (2009) The neurokinin-1 receptor modulates the methamphetamine-induced striatal apoptosis and nitric oxide formation in mice. J Neurochem 111(3):656-668. doi: 10.1111/j.1471-4159.2009.06330.x

Summary: This study examined the role of neurokinin-1 receptors (NK1R) on the methamphetamine-induced apoptosis of striatal neurons. 4 ng of SSP-SAP (Cat. #IT-11) or the control, saporin (Cat. #PR-01), was administered to the striatum of mice. Ablation of NK1R-expressing striatal neurons resulted in a significant reduction of methamphetamine-induced apoptosis. The data suggests that the NK1R circuitry in the striatum may be a target for treatment of methamphetamine abuse.

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