Targeting Topics 13q4

Neurotrophic factors rescue basal forebrain cholinergic neurons and improve performance on a spatial learning test.

Lee YS, Danandeh A, Baratta J, Lin CY, Yu J, Robertson RT.

Exp Neurol 249C:178-186, 2013.

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.

Neurotrophin receptor p75 mediates the uptake of the amyloid beta (Abeta) peptide, guiding it to lysosomes for degradation in basal forebrain cholinergic neurons.

Ovsepian SV, Antyborzec I, O’Leary VB, Zaborszky L, Herms J, Oliver Dolly J.

Brain Struct Funct Epub2013.

Accumulation of β-amyloid in the brain is considered one of the main causes of Alzheimer’s disease. The increase in β-amyloid is accompanied by a reduction in levels of the high affinity nerve growth factor receptor (trkA) and cognitive impairment. The authors looked at levels of the low affinity nerve growth factor receptor (p75) that do not decline. Using a 0.8-μg injection of 192-Cy3 (Cat. #FL-01) into the medial prefrontal cortex of rats the authors assessed the transport of p75 and β-amyloid by microscopy. The results indicate that the primary destinations of both p75 and β-amyloid were the late endosome and lysosome.

P2Y1 receptors expressed by C1 neurons determine peripheral chemoreceptor modulation of breathing, sympathetic activity, and blood pressure.

Wenker IC, Sobrinho CR, Takakura AC, Mulkey DK, Moreira TS.

Hypertension 62(2):263-273, 2013.

Peripheral chemoreceptor activation response is mediated by catecholaminergic C1 cells in the rostral ventrolateral medulla (RVLM). The authors investigated the molecular mechanisms linking this drive to increased sympathetic activity and hypertension through a variety of methods, including lesioning C1 cells in the RVLM. Rats received 4.2-ng bilateral injections of Anti-DBH-SAP (Cat. #IT-03) into the RVLM. Comparison of lesioned animals to controls demonstrated that P2Y1 receptors on C1 cells in the RVLM are key components in the regulation of breathing, sympathetic nerve activity, and blood pressure.

GABAergic Terminals Are a Source of Galanin to Modulate Cholinergic Neuron Development in the Neonatal Forebrain.

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.

Cereb Cortex Epub2013.

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.

Medial Septal Cholinergic Neurons Modulate Isoflurane Anesthesia.

Tai SK, Ma J, Leung LS.

Anesthesiology Epub2013.

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.

Epitopes of the Highly Immunogenic Trichomonas vaginalis alpha-Actinin Are Serodiagnostic Targets for Both Women and Men.

Neace CJ, Alderete JF.

J Clin Microbiol 51(8):2483-2490, 2013.

Trichomonas vaginalis is an anaerobic protozoan that is the most common nonviral causative agent for sexually-transmitted infections. The presence of T. vaginalis in men is usually asymptomatic, making it difficult to assess exposure to the organism. The authors examined sera from exposed individuals for reactivity to specific epitopes of trichomonad α-actinin. A recombinant version of trichonomad α-actinin was constructed and detected using Anti-6His (Cat. #AB-213). Some epitopes were reactive with sera from both men and women, making them potential diagnostic targets.

Leptin-sensitive neurons in the arcuate nucleus integrate activity and temperature circadian rhythms and anticipatory responses to food restriction.

Wiater MF, Li AJ, Dinh TT, Jansen HT, Ritter S.

Am J Physiol Regul Integr Comp Physiol 305(8):R949-R960, 2013.

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.

C1 neurons: the body’s EMTs.

Guyenet PG, Stornetta RL, Bochorishvili G, Depuy SD, Burke PG, Abbott SB.

Am J Physiol Regul Integr Comp Physiol 305(3):R187-204, 2013.

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.

Loss of neurons in rostral ventromedial medulla that express neurokinin-1 receptors decreases the development of hyperalgesia.

Khasabov SG, Simone DA.

Neuroscience 250C:151-165, 2013.

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.

Selective Immunotoxic Lesions of Basal Forebrain Cholinergic Neurons: Twenty Years of Research and New Directions.

Baxter MG, Bucci DJ.

Behav Neurosci Epub2013.

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.

Noggin and Sonic hedgehog are involved in compensatory changes within the motoneuron-depleted mouse spinal cord.

Gulino R, Gulisano M.

J Neurol Sci 332(1-2):102-109, 2013.

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.

Cortical Metabolic Deficits in a Rat Model of Cholinergic Basal Forebrain Degeneration.

Gelfo F, Petrosini L, Graziano A, De Bartolo P, Burello L, Vitale E, Polverino A, Iuliano A, Sorrentino G, Mandolesi L.

Neurochem Res 38(10):2114-2123, 2013.

In this work the authors investigated the connection between cholinergic depletion caused by conditions such as Alzheimer’s disease and cerebral energy metabolism deficits. Rats received a
0.4-μg injection of 192-IgG-SAP (Cat. #IT-01) into the nucleus basalis magnocellularis. Neuronal metabolic activity was measured by assaying cytochrome oxidase (CO) activity. The unilateral injection produced a bilateral deficit in CO activity throughout the cortex, and the front and parietal cortices showed CO deficits before the lesion was complete. The data suggest a link between cholinergic hypofunctionality and metabolic deficit.

Implication of Cerebral Dopamine-beta Hydroxylase for Cardiovascular and Mood Regulation in Rats.

Chang ST, Liu YP, Huang CL, Wang PY, Tung CS.

Chin J Physiol 56(4)2013.

The ascending fibers affected by norepinephrine are involved in a variety of processes, including emotion, anxiety, and regulation of central autonomic outflows such as cardiovascular regulation and energy balance. The authors examined whether the loss of norephinephrine would cause autonomic failure in cardiovascular regulation. Rats received a single intraventricular injection of anti-DBH-SAP (Cat. #IT-03). Saporin (Cat. #PR-01) was used as a control. The results demonstrate that norepinephrine deficits in the brain influence reduction of excitatory responses to orthostatic stress.