2013 Targeting Trends Review

Keimpema E, Zheng K, Barde SS, Berghuis P, Dobszay MB, Schnell R, Mulder J, Luiten PG, Xu ZD, Runesson J, Langel U, Lu B, Hokfelt T, Harkany T (2014) GABAergic terminals are a source of galanin to modulate cholinergic neuron development in the neonatal forebrain. Cereb Cortex 24(12):3277-3288. doi: 10.1093/cercor/bht192

Summary: In this work the authors sought to clarify the role of galanin during brain development. Several different techniques were used including the use of Galanin-SAP (Cat. #IT-34) on primary cell cultures from the fetal forebrains of rats. Cultured basal forebrain neurons were exposed to 5 ng/ml of Galanin-SAP for 8 hours, and cell death was assessed after 72 hours. Cholinergic cells were killed by Galanin-SAP, indicating that these neurons can use extracellular galanin-2 receptors to facilitate development.

Related Products: Galanin-SAP (Cat. #IT-34)

Hartig W, Saul A, Kacza J, Grosche J, Goldhammer S, Michalski D, Wirths O (2014) Immunolesion-induced loss of cholinergic projection neurones promotes beta-amyloidosis and tau hyperphosphorylation in the hippocampus of triple-transgenic mice. Neuropathol Appl Neurobiol 40(2):106-120. doi: 10.1111/nan.12050

Summary: 3xTg transgenic mice were treated with 2 μg of mu p75-SAP (Cat. #IT-16) into the right lateral ventricle to eliminate cholinergic neurons in the basal forebrain. These mice already have age-dependent β-amyloidosis and tau hyperphosphorylation. This new model supplies a potential framework in which to study the entire pathology of Alzheimer’s disease.

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

Tai SK, Ma J, Leung LS (2014) Medial septal cholinergic neurons modulate isoflurane anesthesia. Anesthesiology 120(2):392-402. doi: 10.1097/ALN.0b013e3182a7cab6

Summary: General anesthesia is associated with a decrease in cholinergic function. This work examines the effect of volatile anesthetics such as isoflurane or ketamine in the context of cholinergic depletion. Rats received 105-ng bilateral injections of 192-IgG-SAP (Cat. #IT-01) into the medial septum. Anesthetic effects were evaluated using a loss of righting reflex test. There was no difference between lesioned and control groups in the response to ketamine. When treated with isoflurane, lesioned animals were affected for longer periods of time, and hippocampal response was reduced. The results suggest a role for septal cholinergic neurons in the sensitivity to isoflurane.

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

Guyenet PG, Stornetta RL, Bochorishvili G, Depuy SD, Burke PG, Abbott SB (2013) C1 neurons: the body’s EMTs. Am J Physiol Regul Integr Comp Physiol 305(3):R187-204 . doi: 10.1152/ajpregu.00054.2013

Summary: Although mainly known for their involvement in the control of arterial pressure, C1 neurons are also suspected to participate in numerous other physiological processes such as neuroendocrine response, glucose homeostasis, food consumption, and others. This review discusses the role of these neurons as ’emergency medical technicians’ – cells that produce and modulate physiological survival responses to acute physical stress. The use of Anti-DBH-SAP (Cat. #IT-03) to delineate C1 neurons in the rostral ventrolateral aspect of the medulla oblongata is discussed.

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

Laplante F, Dufresne MM, Ouboudinar J, Ochoa-Sanchez R, Sullivan RM (2013) 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. doi: 10.1002/syn.21612

Summary: The authors examined whether excessive dopamine neurotransmission in the mesolimbic system is due to higher levels of presynaptic or postsynaptic dopamine. Rats received 250-ng bilateral injections of anti-ChAT-SAP (Cat. #IT-42) into the nucleus accumbens. Rabbit IgG-SAP (Cat. #IT-35) was used as a control. The data suggest that reduction of cholinergic interneurons in the nucleus accumbens suppresses presynaptic dopamine release.

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

Read the featured article in Targeting Trends.

Wiater MF, Li AJ, Dinh TT, Jansen HT, Ritter S (2013) Leptin-sensitive neurons in the arcuate nucleus integrate activity and temperature circadian rhythms and anticipatory responses to food restriction. Am J Physiol Regul Integr Comp Physiol 305(8):R949-R960. doi: 10.1152/ajpregu.00032.2013

Summary: The arcuate nucleus (Arc) of the hypothalamus is known to participate in the regulation of feeding, adiposity, and leptin-dependent metabolism. The authors examined the role of leptin-receptive neurons in locomotor and temperature rhythms. Rats received four bilateral injections of Leptin-SAP (Cat. #IT-47) into the Arc; Blank-SAP (Cat. #IT-21) was used as a control. The lesion affected learning connected to light cycles, but not learning connected to food schedules, suggesting a mechanism for internal desynchrony that might play a role in obesity and other metabolic disorders.

Related Products: Leptin-SAP (Cat. #IT-47), Blank-SAP (Cat. #IT-21)

Khasabov SG, Simone DA (2013) Loss of neurons in rostral ventromedial medulla that express neurokinin-1 receptors decreases the development of hyperalgesia. Neuroscience 250C:151-165. doi: 10.1016/j.neuroscience.2013.06.057

Summary: Previous data has indicated that neurokinin-1 receptors are located on ON cells in the rostral ventromedial medulla (RVM). ON cells are considered pronociceptive because noxious stimulation is stimulatory. In this work the authors eliminated ON cells using 0.3-μl injections of 1 μM SSP-SAP (Cat. #IT-11) into the left and right side of the RVM. Blank-SAP (Cat. #IT-21) was used as a control. SSP-SAP treatment did not change mechanical or heat withdrawal responses, or change morphine-induced analgesia. A significant reduction in the duration of nocifensive behaviors induced by various hyperalgesic stimulators indicated that these neurons are involved in pain facilitation rather than modulation.

Related Products: SSP-SAP (Cat. #IT-11), Blank-SAP (Cat. #IT-21)

Baxter MG, Bucci DJ (2013) Selective immunotoxic lesions of basal forebrain cholinergic neurons: twenty years of research and new directions. Behav Neurosci 127(5):611-618 . doi: 10.1037/a0033781

Summary: This review covers twenty years of basal forebrain cholinergic lesioning. The initial use of 192-IgG-SAP (Cat. #IT-01) is discussed, as well as other immunotoxins such as GAT-1-SAP (Cat. #IT-32) and OX7-SAP (Cat. #IT-02). The findings generated by the use of 192-IgG-SAP and how those data have helped forward the understanding of how the cholinergic system functions in the basal forebrain are detailed. The authors also discuss new directions in the field.

Related Products: 192-IgG-SAP (Cat. #IT-01), OX7-SAP (Cat. #IT-02), GAT1-SAP (Cat. #IT-32)

Gulino R, Gulisano M (2013) Noggin and Sonic hedgehog are involved in compensatory changes within the motoneuron-depleted mouse spinal cord. J Neurol Sci 332(1-2):102-109. doi: 10.1016/j.jns.2013.06.029

Summary: Noggin (NOG) and Sonic hedgehog (Shh) are both involved in the generation and organization of neural tissues. In order to clarify the role of these two proteins in the regulation of neurogenesis and/or neuroplasticity the authors used a motoneuron depletion model in the mouse spinal cord. 3 μg of CTB-SAP (Cat. #IT-14) was injected into each of the medial and lateral gastrocnemius muscles and the expression of NOG and Shh were monitored. Motor performance also correlated with NOG and Shh levels, indicating that these proteins could play roles in regeneration and functional restoration.

Related Products: CTB-SAP (Cat. #IT-14)

Lee YS, Danandeh A, Baratta J, Lin CY, Yu J, Robertson RT (2013) Neurotrophic factors rescue basal forebrain cholinergic neurons and improve performance on a spatial learning test. Exp Neurol 249C:178-186. doi: 10.1016/j.expneurol.2013.08.012

Summary: It is thought that therapeutic treatments of the cholinergic system may be a viable treatment for Alzheimer’s disease. In order to examine this hypothesis the authors administered a total of 160 ng of 192-IgG-SAP (Cat. #IT-01) in the form of bilateral injections into the medial septum. The lesioned animals then received 4-week infusions of nerve growth factor, neurotrophin 3, or both into the lateral ventricles. Animals treated with any neurotrophin, either alone or as a combination, retained more ChAT-positive neurons and performed better on a delayed match-to-position task than control animals. The data strengthen the theory that exogenous neurotrophic factors ameliorate the effects of Alzheimer’s disease.

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