Targeting Topics 15q3

Targeted ablation of cholinergic interneurons in the dorsolateral striatum produces behavioral manifestations of Tourette syndrome.

Xu M, Kobets A, Du JC, Lennington J, Li L, Banasr M, Duman RS, Vaccarino FM, DiLeone RJ, Pittenger C.

Proc Natl Acad Sci U S A 112(3):893-898, 2015.

Postmortem studies of Tourette syndrome patients has revealed a reduction in the number of specific striatal interneurons. The authors explored the hypothesis that this neuronal deficit is enough to produce the symptoms of Tourette syndrome in mice. Animals received 90-ng injections of Anti-ChAT-SAP (Cat. #IT-42) into the striatum. Rabbit IgG-SAP (Cat. #IT-35) was used as a control. The data suggest that loss of the striatal interneurons is enough to produce some, but not all, of the symptoms caused by Tourette syndrome.

Role of striatal cholinergic interneurons in set-shifting in the rat.

Aoki S, Liu AW, Zucca A, Zucca S, Wickens JR.

J Neurosci 35(25):9424-9431, 2015.

The authors examined the role that cholinergic interneurons in the striatum play in a process called strategy set-shifting, where an attentional shift is required. Rats received bilateral injections of Anti-ChAT-SAP (Cat. #IT-42) into either the dorsomedial striatum or ventral striatum (500 ng total). Initial task learning was unaffected by either lesion. Lesioned animals displayed set-shifting deficits, and the deficit characteristics depended on the location of the lesion.

A central role for spinal dorsal horn neurons that express neurokinin-1 receptors in chronic itch.

Akiyama T, Nguyen T, Curtis E, Nishida K, Devireddy J, Delahanty J, Carstens MI, Carstens E.

Pain 156(7):1240-1246, 2015.

Chronic itch is caused by increased sensitivity of itch-signaling pathways. It can be generated by normally itchy stimuli (hyperknesis) and by normally non-itchy light touch (alloknesis). The authors used an ovalbumin-induced atopic dermatitis model to study chronic itch in mice. The mice received 400-ng intrathecal injections of Bombesin-SAP (Cat. #IT-40), SSP-SAP (Cat. #IT-11), or the control Blank-SAP (Cat. #IT-21). While Bombesin-SAP significantly attenuated hyperknesis, it had no effect on spontaneous scratching or alloknesis. SSP-SAP reduced all behavioral signs of chronic itch.

Neurokinin 3 Receptor-Expressing Neurons in the Median Preoptic Nucleus Modulate Heat-Dissipation Effectors in the Female Rat.

Mittelman-Smith MA, Krajewski-Hall SJ, McMullen NT, Rance NE.

Endocrinology 156(7):2552-2562, 2015.

Kisspeptin and Neurokinin B (NKB) expression in the infundibular, or arcuate, nucleus is increased after menopause. Here the authors investigate whether KNDy (kisspeptin, NKB, and dynorphin expressing) neurons are able to influence cutaneous vasodilation through Neurokinin 3 (NK3)-expressing projections from the median preoptic nucleus (MnPO). Rats received two 10-ng injections of NK3-SAP (Cat. #IT-63) into the MnPO. Blank-SAP (Cat. #IT-21) was used as a control. The data indicate that NK3-expressing neurons in the MnPO facilitate vasodilation.

Hindbrain catecholamine neurons activate orexin neurons during systemic glucoprivation in male rats.

Li AJ, Wang Q, Elsarelli MM, Brown RL, Ritter S.

Endocrinology 156(8):2807-2820, 2015.

Norepinephrine and epinephrine-secreting catecholamine neurons are strong stimulators of food intake. The authors investigated the interaction between these catecholamine neurons and orexin neurons in the perifornical lateral hypothalamus (PeFLH), which are known to be involved with the stimulation of food intake, increased arousal, and behavioral activation. Rats received 82-ng injections of Anti-DBH-SAP (Cat. #IT-03) into the PeFLH terminal field in order to lesion catecholamine neurons. Saporin (Cat. #PR-01) was used as a control. Assessment of food intake in response to 2-deoxy-D-glucose, as well as selective catecholamine activation, indicated that orexin neuron activation may be involved in glucoprivic appetite responses.

Orexin-A Enhances Feeding in Male Rats by Activating Hindbrain Catecholamine Neurons.

Li AJ, Wang Q, Davis H, Wang R, Ritter S.

Am J Physiol Regul Integr Comp Physiol Epub:ajpregu.00065.2015, 2015.

Although administration of orexin, norepinephrine, and epinephrine all induce significantly increased food intake, the potential interaction between the networks affected by these molecules has not been studied. In this work, the authors investigate the hypothesis that orexin neurons may stimulate feeding through the activation of catecholamine neurons. Rats received 82-ng injections of Anti-DBH-SAP (Cat. #IT-03) into the hypothalamus in order to lesion hypothalamically-projecting catecholamine neurons. Saporin (Cat. #PR-01) was used as a control. While the normal response to orexin A is increased food intake, lesioned animals did not display this response, indicating that catecholamine neurons are necessary for orexin modulation of food intake.

Selective optogenetic stimulation of the retrotrapezoid nucleus in sleeping rats activates breathing without changing blood pressure or causing arousal or sighs.

Burke PG, Kanbar R, Viar KE, Stornetta RL, Guyenet PG.

J Appl Physiol (1985) 118(12):1491-1501, 2015.

Hypoxia and hypercapnia both play roles in the activation of normal breathing. If either one is severe enough, arousal will also occur. The authors looked to better define the CNS pathways utilized by hypoxia and hypercapnia, as well as the pathways responsible for activation of arousal due to these conditions. The authors used optogenetic activation of the retrotrapezoid nucleus and C1 and A5 catecholaminergic neurons, as well as selective C1 neuron stimulation in rats. Some rats also received bilateral injections of Anti-DBH-SAP (Cat. #IT-03) totaling 0.88 μg into the region of the lateral horn of the second thoracic segment.

Role of cerebrospinal fluid-contacting nucleus in sodium sensing and sodium appetite.

Xing D, Wu Y, Li G, Song S, Liu Y, Liu H, Wang X, Fei Y, Zhang C, Li Y, Zhang L.

Physiol Behav 147:291-299, 2015.

Sodium concentration in the cerebrospinal fluid (CSF) is tightly regulated, and this regulation requires numerous sensors spread throughout the brain. Here the authors injected 900 ng CTB-SAP (Cat. #IT-14) into the lateral ventricles. Investigation of spontaneous and induced sodium intake indicates the CSF-contacting nucleus is an important link in the sodium sensing network, and interacts with the lateral parabrachial nucleus.

Inflammatory Macrophages Promotes Development of Diabetic Encephalopathy.

Wang B, Miao Y, Zhao Z, Zhong Y.

Cell Physiol Biochem 36(3):1142-1150, 2015.

Diabetes can cause neuroinflammation leading to dementia. Diabetes was induced in mice by injection of streptozotocin (STZ). In order to investigate the role of inflammatory macrophages in the development of diabetic encephalopathy, the authors used twice weekly 20-μg IP injections of Mac-1-SAP (Cat. #IT-06). Mice receiving Mac-1-SAP had significantly reduced numbers of inflammatory macrophages in the brain, and also reduced responses to STZ injection.

Striatal patch compartment lesions reduce stereotypy following repeated cocaine administration.

Murray RC, Logan MC, Horner KA.

Brain Res Epub2015.

Stereotypy is defined as abnormally repetitive motor movements accompanied by an inability to initiate normal adaptive responses. Psychostimulants such as cocaine will often produce these movements. It is thought that stereotypy is related to activation of the patch compartment of the striatum. In order to better understand the function of the patch compartment in stereotypy due to repeated exposure to cocaine, the authors administered bilateral injections of Dermorphin-SAP (Cat. #IT-12) into the rostral striatum. Saporin (Cat. #PR-01) was used as a control.

Role of adrenomedullin in the cerebrospinal fluid-contacting nucleus in the modulation of immobilization stress.

Wu YH, Song SY, Liu H, Xing D, Wang X, Fei Y, Li GL, Zhang C, Li Y, Zhang LC.

Neuropeptides 51:43-54, 2015.

The CSF-contacting nucleus (CSF-CN) is a brain structure containing neurons that can bidirectionally transmit signals between the brain parenchyma and the CSF. In order to better understand what regulatory peptides modulate this organ, the authors eliminated the CSF-CN of rats with a 500-ng icv injection of CTB-SAP (Cat. #IT-14). Saporin (Cat. #PR-01) was used as a control. The elimination of the CSF-CN worsened the response to chronic immobilization stress; with other data this information suggests that the CSF-CN uses adrenomedullin as a stress-related peptide.

Treatment Considerations for Cancer Pain: A Global Perspective.

Pergolizzi JV, Gharibo C, Ho KY.

Pain Pract Epub2014.

This review discusses the treatment of cancer pain, addressing various aspects of the overall picture, such as early pain treatment to reduce central sensitization and chronic pain, pain assessment tools, and guidelines for treating specific populations of patients. Some of the current tools for pain management are discussed, including SP-SAP, which is currently in clinical trials as a cancer pain therapeutic (see cover article).

Novel Mechanisms of Spinal Cord Plasticity in a Mouse Model of Motoneuron Disease.

Gulino R, Parenti R, Gulisano M.

Biomed Res Int 2015:654637, 2015.

Here the authors investigate spinal plasticity mechanisms involving a number of different proteins, including BDNF, Shh, Notch-1, Numb, and Noggin. The model used is a mouse motoneuron depletion strategy, where the animals receive 3 μg of CTB-SAP (Cat. #IT-14) into each of the medial and lateral gastrocnemius muscles. The results indicate that TDP-43, a nuclear DNA/RNA binding protein, may be an important regulator of synaptic plasticity.

Effects of immunotoxic and electrolytic lesions of medial septal area on spatial short-term memory in rats.

Dashniani M, Kruashvili L, Rusadze Kh, Mataradze S, Beselia G.

Georgian Med News (239):98-103, 2015.

In this work the authors investigated how essential septohippocampal projections are in a spatial working memory model. Rats received bilateral injections of 192-IgG-SAP (Cat. #IT-01, 600 ng total) or GAT-1-SAP (Cat. #IT-32, 195 ng total) into the medial septum. Saporin (Cat. #PR-01) was used as a control.

Selective lesion of gaba-ergic neurons in the medial septum by gat1-saporin impairs spatial learning in a water-maze.

Burjanadze M, Mataradze S, Rusadze K, Chkhikvishvili N, Dashniani M.

Georgian Med News (240):59-64, 2015.

The authors investigated the role of GABAergic neurons in the medial septum on spatial learning using a Morris water maze test. Rats received bilateral injections totaling 162 ng of GAT-1-SAP (Cat. #IT-32) into the medial septum. Saporin (Cat. #PR-01) was used as a control. The lesioned animals displayed significant deficits during the water maze task, indicating that GABAergic neurons in the medial septum are intrinsic to organization of spatial map-driven behavior.

Exploratory behavior and recognition memory in medial septal electrolytic, neuro- and immunotoxic lesioned rats.

Dashniani MG, Burjanadze MA, Naneishvili TL, Chkhikvishvili NC, Beselia GV, Kruashvili LB, Pochkhidze NO, Chighladze MR.

Physiol Res Epub2015.

To investigate recognition memory that incorporates a spatial or temporal component, the authors lesioned the medial septum of rats using several techniques. For specific lesioning of cholinergic neurons rats received bilateral injections of 192-IgG-SAP (Cat. #IT-01, 500 ng total) into the medial septum. Saporin (Cat. #PR-01) was used as a control. While electrolytic lesions produced disruptions of spatial recognition memory, immunotoxin lesions did not, indicating that the cholinergic neurons of the septohippocampal pathway are not essential to processing this type of learning.