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A large body of evidence suggests that the neuropeptide galanin plays an important role in seizure control. In line with this, it was demonstrated that the galanin analogue, NAX-5055, exerts a potent anticonvulsant activity in animal seizure models. We recently found that the NAX-5055-mediated anticonvulsant action involves modulation of both excitatory and inhibitory neurotransmission. Since homeostasis of neurotransmitters and cerebral energy metabolism are intimately linked, it was investigated whether the effects of NAX-5055 on neurotransmission involve changes in energy metabolism and in particular glucose- and amino acid metabolism. With this aim, cultured neurons from mouse brain were incubated with [U- 13 C]glucose in absence or presence of NAX-5055. Since effects of NAX-5055 on neurotransmission were detected during repetitive stimulation, we tested potential metabolic effects while mimicking repetitive bursts of neurotransmitter release as occurring in the intact brain. The metabolic pathways were mapped using gas-chromatography coupled to mass-spectrometry. We found that NAX-5055 does not modify glucose metabolism in glutamatergic and GABAergic neurons. Furthermore, the effect of NAX-5055 on astrocyte-neuron metabolic interactions was investigated by incubating co-cultures of astrocytes and either glutamatergic or GABAergic neurons with [U- 13 C]glucose or the glial-selective substrate [1,2- 13 C]acetate, with or without NAX-5055. In the presence of NAX-5055, no changes in the metabolic landscape were traced. The findings suggest that the anticonvulsant action of NAX-5055 and the accompanying changes in neurotransmission do not involve alterations in energy and amino acid metabolism. Hence, NAX-5055 appears to be an anti-seizure drug candidate displaying no unwanted side effects concerning brain energy and amino acid homeostasis. © 2017 Wiley Periodicals, Inc., (© 2017 Wiley Periodicals, Inc.)

Evidence indicates that central galanin is involved in regulation of insulin resistance in animals. This study investigates whether type 1 galanin receptor (GAL1) in the brain mediates the ameliorative effect of galanin on insulin resistance in skeletal muscles of type 2 diabetic rats. Rats were intracerebroventricularly (i.c.v.) injected with galanin(1-13)-bradykinin(2-9) amide (M617), a GAL1 agonist, and/or Akti-1/2, an Akt inhibitor, via caudal veins once per day for 10 days. Insulin resistance in muscle tissues was evaluated by glucose tolerance and 2-[N-(7-nitrobenz-2-oxa-1,3-diazol-4-yl)amino]-2-deoxyglucose (2-NBDG) tests, peroxisome proliferator-activated receptor-γ (PPARγ), glucose transporter 4 (GLUT4) mRNA expression levels, Akt phosphorylation, and GLUT4 and vesicle-associated membrane protein 2 (VAMP2) concentration at plasma membranes in muscle cells. The results show that i.c.v. treatment with M617 increased glucose tolerance, 2-NBDG uptake, PPARγ levels, Akt phosphorylation, GLUT4 protein, and GLUT4 mRNA expression levels as well as GLUT4 and VAMP2 concentration at plasma membranes. All increases may be blocked by pretreatment with Akti-1/2. These results suggest that activated central GAL1 may trigger the Akt signaling pathway to alleviate insulin resistance in muscle cells. Therefore, the impact of galanin on insulin resistance is mediated mainly by GAL1 in the brain, and the GAL1 agonist may be taken as a potential antidiabetic agent for treatment of type 2 diabetes mellitus. © 2016 Wiley Periodicals, Inc., (© 2016 Wiley Periodicals, Inc.)

Although the tuberomammillary nucleus (TM) is well defined in terms of anatomy and neurochemistry, little is known about its function in nociceptive modulation. There was an abundance of galanin-immunoreactive fibers in the TM, and galanin has been implicated in pain processing. The present study assessed the role of galanin in the modulation of nociception in the TM of rats. Intra-TM injection of galanin dose-dependently increased the hindpaw withdrawal latency of rats to a noxious thermal stimulus, indicating an antinociceptive role of galanin in the TM. The antinociceptive effect of galanin was blocked by a subsequent intra-TM injection of galantide, a putative galanin receptor antagonist, suggesting that the antinociceptive effect of galanin is mediated by galanin receptors. Moreover, there was abundant galanin receptor 1 (GalR1) in the TM, and the number of GalR1-positive neurons in the ipsilateral TM increased significantly after unilateral loose ligation of the sciatic nerve compared with the contralateral TM or the TM of intact rats. However, the number of GalR1-positive neurons was not significantly altered by carrageenan-induced inflammation, in either the ipsilateral or the contralateral TM. The results suggest that galanin and GalR1 in the TM may play important roles in pain regulation.