targeted-toxins

Szigeti C, Bencsik N, Simonka AJ, Legradi A, Kasa P, Gulya K (2013) Long-term effects of selective immunolesions of cholinergic neurons of the nucleus basalis magnocellularis on the ascending cholinergic pathways in the rat: A model for Alzheimer’s disease. Brain Res Bull 94C:9-16. doi: 10.1016/j.brainresbull.2013.01.007

Summary: 192-IgG-SAP (Cat. #IT-01) has been used extensively to generate models of Alzheimer’s disease in rats. In this work, the authors detailed the time course of neuronal loss with an eye on potential recovery from the lesion. The nucleus basalis magnocellularis of rats was injected with 75 ng of 192-IgG-SAP (Cat. #IT-01) and long-term changes were tracked by immunohistochemistry. While some acetylcholinesterase neurons, considered cholinoceptive, were lost, choline acetyltransferase (cholinergic) neurons sustained a massive irreversible reduction in number.

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

Hamlin AS, Windels F, Boskovic Z, Sah P, Coulson EJ (2013) Lesions of the basal forebrain cholinergic system in mice disrupt idiothetic navigation. PLoS One 8(1):e53472. doi: 10.1371/journal.pone.0053472

Summary: Alzheimer’s disease patients perform poorly on spatial navigation tests requiring either distal cues (allothetic) or body-centered cues (idiothetic). The authors used 0.2 μg bilateral infusions of mu p75-SAP (Cat. #IT-16) into the lateral ventricles of mice to examine the hypothesis that the cholinergic medial septo-hippocampal circuit is important for idiothetic navigation. Rabbit IgG-SAP (Cat. #IT-35) was used as a control. Lesioned animals were similar to controls in contextual fear conditioning, spatial working memory, as well as several other parameters. But exploratory behavior requiring idiothetic signals was very disorganized, indicating that cholinergic cells are vital to idiothetic navigation.

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

Ferrini F, Trang T, Mattioli TA, Laffray S, Del’Guidice T, Lorenzo LE, Castonguay A, Doyon N, Zhang W, Godin AG, Mohr D, Beggs S, Vandal K, Beaulieu JM, Cahill CM, Salter MW, De Koninck Y (2013) Morphine hyperalgesia gated through microglia-mediated disruption of neuronal Cl(-) homeostasis. Nat Neurosci 16(2):183-192. doi: 10.1038/nn.3295

Summary: Although morphine is the drug of choice in dealing with chronic pain, it paradoxically can produce a hyperalgesic state. The authors examined the issue from several different angles. One method was to eliminate spinal microglia of rats through the intrathecal application of 16-32 μg of Mac-1-SAP (Cat. #IT-33). 20 μg of saporin (Cat. #PR-01) was used as a control. It was found that P2X4 receptors expressed by microglia were necessary for the development of morphine hyperalgesia, but not morphine tolerance.

Related Products: Mac-1-SAP rat (Cat. #IT-33), Saporin (Cat. #PR-01)

Read the featured article in Targeting Trends.

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)

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)

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)

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)