Targeting Topics 10q3

Hindbrain Catecholamine Neurons Modulate the Growth Hormone But Not the Feeding Response to Ghrelin

Emanuel AJ, Ritter S

Endocrinology 151(7):3237-3246, 2010.

In this work the authors investigated the role of hindbrain catecholamine neurons in the response to a gastrointestinal peptide, ghrelin. Rats received 42-ng injections of anti-DBH-SAP (Cat. #IT-03) into the paraventricular nucleus of the hypothalamus. Saporin (Cat. #PR-01) was used as a control. Lesioned animals had a prolonged growth hormone (GH) response to ghrelin administration as compared to controls, but the feeding response was unchanged. The results indicate that ghrelin or GH may be involved with a negative feedback response controlling GH levels.

BMP9 (bone morphogenetic protein 9) induces NGF as an autocrine/paracrine cholinergic trophic factor in developing basal forebrain neurons

Schnitzler AC, Mellott TJ, Lopez-Coviella I, Tallini YN, Kotlikoff MI, Follettie MT, Blusztajn JK

J Neurosci 30(24):8221-8228, 2010.

Bone morphogenetic protein (BMP) 9 is a cholinergic differentiation factor that increases acetylcholine synthesis and choline acetyltransferase gene expression. The authors investigated whether BMP9 could induce cholinergic trophic factors in murine septal cells. One experiment involved the sorting of E18 septal cells using anti-p75 (Cat. #AB-N01AP, 5 µg/2 x 10 6 cells). The increased NGF gene expression in response to BMP9 in p75-positive basal forebrain cholinergic neurons indicates an autocrine/paracrine role for NGF in the development and maintenance of these cells.

Hyperalgesic priming is restricted to isolectin B4-positive nociceptors

Joseph EK, Levine JD

Neuroscience 169(1):431-435, 2010.

Hyperalgesic priming is an injury that induces a chronic pain state marked by the presence of inflammatory cytokines. The authors evaluated which populations of nociceptors are involved in the priming process. Rats that received 3.2-µg intrathecal injections of IB4-SAP (Cat. #IT-10) failed to establish priming. Acute mechanical hyperalgesia could still be induced, indicating that IB4+ nociceptors are necessary for priming, but a different nociceptor group is involved with nociceptor sensitization.

Expression of cell fate determinants and plastic changes after neurotoxic lesion of adult mice spinal cord by cholera toxin-B saporin

Gulino R, Perciavalle V, Gulisano M

Eur J Neurosci 31(8):1423-1434, 2010.

Sonic hedgehog, Notch-1, and Numb are proteins known to be involved in the function of stem cells. Understanding of how they might work in adults may provide methods to improve recovery from spinal cord injury. In this work the authors injected 3 µg of CTB-SAP (Cat. #IT-14) into the medial and lateral gastrocnemius muscles of mice. Analysis of protein levels following motoneuron depletion gives some insight into the molecular framework of nerve injury. (See cover article.)

Utilization of the least shrew as a rapid and selective screening model for the antiemetic potential and brain penetration of substance P and NK1 receptor antagonists

Darmani NA, Wang Y, Abad J, Ray AP, Thrush GR, Ramirez J

Brain Res 1214:58-72, 2008.

This work investigated the role of central tachykinin NK1 receptors in delayed phase vomiting caused by chemotherapeutics. Least shrews received 1.2 mg/kg intraperitoneal injections of SSP-SAP (Cat. #IT-11). Saporin (Cat. #PR-01) and blank-SAP (Cat. #IT-21) were used as controls. In response to administration of a NK1 receptor agonist, lesioned animals vomited less than the control group, indicating an important role for NK1 receptors in emesis.

Orexin mediates initiation of sexual behavior in sexually naive male rats, but is not critical for sexual performance

Di Sebastiano AR, Yong-Yow S, Wagner L, Lehman MN, Coolen LM

Horm Behav 58(3):397-404, 2010.

In this work the role of endogenous orexin A and B in male sexual behavior was investigated. Rats received a total of 400 ng of orexin-SAP (Cat. #IT-20, discontinued) into the hypothalamus in each hemisphere. Blank-SAP (Cat. #IT-21) was used as a control. The lesions facilitated initiation of sexual behavior in naïve males, and reduced anxiety-like behaviors. The data suggest that orexin may play a role in arousal and anxiety related to sexual behavior in naïve animals, but is not critical for performance or motivation.

Selective Lesion of the Developing Central Noradrenergic System: Short- and Long-Term Effects and Reinnervation by Noradrenergic-Rich Tissue Grafts

Coradazzi M, Gulino R, Garozzo S, Leanza G

J Neurochem 114(3):761-771, 2010.

The authors removed noradrenergic neurons in the locus coeruleus/subcoeruleus complex of neonatal rats with 0.25-1.0 µg bilateral injections of anti-DBH-SAP (Cat. #IT-03). No damage was seen in dopaminergic, adrenergic, serotonergic, or cholinergic neurons after this treatment. Rats receiving fetal locus coeruleus tissue implants showed significant post-lesion recovery suggesting that this model can be used to investigate compensatory reinnervation and functional recovery in the central nervous system.

Pain is a salient “stressor” that is mediated by corticotropin-releasing factor-1 receptors

Hummel M, Cummons T, Lu P, Mark L, Harrison JE, Kennedy JD, Whiteside GT

Neuropharmacology 59(3):160-166, 2010.

Given that corticotrophin-releasing factor (CRF) plays a major role in the response to stress, the authors investigated the role CRF-1 receptors may play in the perception of pain. Both rats and mice received 10 µl-intrathecal injections of 10-µM CRF-SAP (Cat. #IT-13) following a spinal nerve ligation. Administration of CRF-SAP attenuated tactile hypersensitivity, indicating that CRF-1 receptors are involved in pain perception.

Endogenous Histamine Facilitates Long-Term Potentiation in the Hippocampus during Walking

Luo T, Leung LS

J Neurosci 30(23):7845-7852, 2010.

The neurotransmitter histamine is involved in several physiological functions, such as sleep-wake activites, circadian rhythms, learning, and memory. This work examines the role of histamine in modulating synaptic plasticity. Rats received 62.5 ng injections of orexin-SAP (Cat. #IT-20, discontinued) into the tuberomammillary nucleus (TMN), followed by assessment of long term potentiation (LTP) during different behavioral states. The data indicate that histaminergic neurons in the TMN facilitate basal-dendritic LTP during walking.

Estrogen therapy and cognition: a review of the cholinergic hypothesis

Gibbs RB

Endocr Rev 31(2):224-253, 2010.

This review discusses estrogen therapy for use in postmenopausal women. In this context the issues revolve around benefits vs. harm of such therapy on the brain and cognitive impairment associated with aging and Alzheimer’s disease. Use of 192-IgG-SAP (Cat. #IT-01) to investigate this paradigm is described.

Gene expression profile in rat hippocampus with and without memory deficit

Paban V, Farioli F, Romier B, Chambon C, Alescio-Lautier B

Neurobiol Learn Mem 94(1):42-56, 2010.

This work examined a wide range of gene expression in the rat hippocampus after bilateral injections of 192-IgG-SAP (Cat. #IT-01) – 37.5 ng per side in medial septum and 75 ng per side in nucleus basalis magnocellularis. Memory loss following 192-IgG-SAP treatment was marked by gene expression that did not show the same cluster organization as learning processes. Genes showing differential expression were down-regulated, and one cluster associated with tissue remodeling could be identified.

Role of neurokinin-1 expressing neurons in the locus coeruleus on ventilatory and cardiovascular responses to hypercapnia

de Carvalho D, Bicego KC, de Castro OW, da Silva GS, Garcia-Cairasco N, Gargaglioni LH

Respir Physiol Neurobiol 172(1-2):24-31, 2010.

NK-1 receptors (NK1R) play an important role in cardiorespiratory responses to hypercapnia. In order to paint a clearer picture of the systems involved the authors injected 0.4 µl of 2-µM SP-SAP (Cat. #IT-07) into the locus coeruleus (LC) of rats. Mouse IgG-SAP (Cat. #IT-18) was used as a control. The data suggest that several subpopulations of neurons express NK1R in the LC, and that these subpopulations play different roles in the modulation of cardiorespiratory reponses to hypercapnia.

Splanchnic sympathectomy prevents translocation and spreading of E coli but not S aureus in liver cirrhosis

Worlicek M, Knebel K, Linde HJ, Moleda L, Scholmerich J, Straub RH, Wiest R

Gut 59(8):1127-1134, 2010.

Advanced cirrhosis activates the sympathetic nervous system. This work investigates the role of the sympathetic nervous system (SNS) in spontaneous bacterial peritonitis – which is mainly caused by translocation of enteric Gram-negative bacteria. Rats received 15-µg intraperitoneal injections of anti-DBH-SAP (Cat. #IT-03). Lesioned animals displayed increased susceptibility to bacterial translocation and infection with E. coli but not S. aureus. This suggests the SNS plays an important role in the immune response to Gram-negative bacteria.

Noradrenergic neurons of the area postrema mediate amylin’s hypophagic action

Potes CS, Turek VF, Cole RL, Vu C, Roland BL, Roth JD, Riediger T, Lutz TA

Am J Physiol Regul Integr Comp Physiol 299(2):R623-31, 2010.

Amylin decreases food intake in rats and is a satiation signal affecting the area postrema (AP). This work investigated the role of noradrenergic neurons in amylin activity. Rats received a total of 50 ng of anti-DBH-SAP (Cat. #IT-03) into the AP and 25 ng into the lateral parabrachial nucleus. Mouse IgG-SAP (Cat. #IT-18) was used as a control. Rats showing a >50% lesion of noradrenergic neurons were unresponsive to low doses of amylin, suggesting that noradrenergic neurons are part of the amylin pathway.

Targeted Ablation of Mesenteric Projecting Sympathetic Neurons Reduces the Hemodynamic Response to Pain in Conscious Spinal Cord Transected Rats

Lujan HL, Palani G, Peduzzi J, Dicarlo SE

Am J Physiol Regul Integr Comp Physiol 298(5):R1358-1365, 2010.

Autonomic dysreflexia is a life-threatening hypertension as a result of a spinal cord injury above thoracic level 6. The authors investigated whether reduction of sympathetic activity can reduce the severity of this condition. Rats received 13.5-µg injections of CTB-SAP (Cat. #IT-14) into the celiac ganglion resulting in ablation of mesenteric-projecting sympathetic neurons. Lesioned animals displayed a reduced pressor response to pain after spinal cord transection, to some extent ameliorating autonomic dysreflexia.