Galanin Treatment Research Articles

Effects of central galanin administration on muscarinic cholinergic and galanin receptor G protein coupling

The neuropeptide galanin is expressed in the mammalian central nervous system and has been implicated in neurotrophic actions. Central galanin administration induces cognitive deficits in rodents and inhibits the release of acetylcholine in the hippocampus. In addition, a galanin hyperinnervation of the basal forebrain cholinergic cells in Alzheimer's disease patients has been reported. To evaluate the effect of galanin treatment on galanin and muscarinic cholinergic receptor G protein coupling, galanin was administered into the lateral ventricle of rats via an implanted cannula. Galanin or muscarinic receptor functional coupling to G proteins was quantified by galanin or carbachol stimulation of guanosine 5'-(gamma-[35S]thio)triphosphate binding in rat brain slices. Guanosine 5'-(gamma-[35S]thio)triphosphate basal binding in nucleus basalis of Meynert and thalamic nuclei was increased in the vehicle treated group. This effect was reverted by galanin treatment and indicates that the surgery increased receptor functional coupling to G proteins, which is restored by a possible neurotrophic action mediated by galanin. In addition, in galanin administered animals, galanin-stimulated binding was increased in the amygdala but decreased in the diagonal band, whilst binding stimulation mediated by carbachol was found to be increased in the amygdala, thalamic nuclei and diagonal band. These findings indicate that galanin treatment modulates the coupling of galanin and muscarinic cholinergic receptors to G proteins in specific regions of the rat central nervous system.

Galanin in neuro(glio)genesis: expression of galanin and receptors by progenitor cells in vivo and in vitro and effects of galanin on neurosphere proliferation

Considerable recent evidence suggests that in addition to its neuromodulatory role, galanin, like several other neuropeptides, also plays an important trophic role during development and after adult neural injury. Studies in our laboratory have identified high levels of galanin and galanin receptor expression in the subventricular zone, rostral migratory stream, subgranular zone of dentate gyrus and the medial corpus callosum--which include the main sites for continuing cell proliferation in both adult and developing rat brain. Galanin expression was also strongly and transiently induced in oligodendrocyte progenitor cells (OPCs) throughout the neocortex and corpus callosum by a benign physiological stimulus, cortical spreading depression (CSD). SD-like depolarization also occurs in peri-infarction areas following cerebral ischemia and is associated with proliferation of OPCs and transiently increased galanin expression. Together, these data suggest a putative role for galanin in regulating progenitor or 'stem cell' proliferation, migration and/or differentiation. Cultured adult and embryonic stem cells or 'neurospheres' express galanin and galanin receptor mRNA and preliminary studies suggest that sub-acute galanin treatment of cultured neurospheres decreases cell proliferation/survival, possibly by effects on the rate of apoptosis via GalR2 receptors.

Galanin inhibits leptin expression and secretion in rat adipose tissue and 3T3-L1 adipocytes.

In addition to serving as a fat depot, adipose tissue is also considered as an important endocrine organ that synthesizes and secretes a number of factors. Leptin is an adipocyte-derived hormone that plays a vital role in energy balance. Expression of leptin is regulated by dietary status and hormones. In the present study, we report that galanin, an orexigenic peptide, inhibits leptin expression and secretion in rat adipose tissue and in 3T3-L1 adipocytes. Treatment with galanin (25 micro g/animal) induced approximately 46% down-regulation of leptin secretion at 15 min, followed by 40, 37 and 47% decreases in leptin secretion at 1, 2 and 4 h respectively. Although Northern blot analysis of adipose tissue from the same animals showed that leptin mRNA expression in adipose tissue was unaffected by galanin treatment for 2 h, galanin treatment for 4 h led to decline of leptin mRNA expression in a dose-dependent manner. Meanwhile, treating the rats with galanin had no effect on leptin mRNA expression in the hypothalamus. The inhibitory action of the galanin on leptin mRNA and protein levels was also observed in vitro. When incubated with 10 nM galanin for 48 h, leptin mRNA expression and protein secretion also decreased in 3T3-L1 adipocytes. On the other hand, galanin was found not only to express in rat adipose tissue, but also to increase about 8-fold after fasting. Based on these data, we speculate that increased galanin expression in rat adipose tissue after fasting may be involved in reducing leptin expression and secretion in fasting rats.

Rat strain differences in response to galanin on the Morris water task

Galanin acts as an inhibitory modulator of cholinergic transmission in the septohippocampal pathway of the rat. Centrally administered galanin induces performance deficits on rodent learning and memory tasks, including delayed non-matching to position, T-maze delayed alternation, passive avoidance, starbust radial maze acquisition, and the Morris water task. The present study investigates differences in responsiveness to intraventricularly administered galanin across three strains of laboratory rat on acquisition of spatial learning in the Morris water task. Sprague–Dawley rats showed normal performance during training, but lack of selective quadrant search on the probe trial in response to galanin treatment. Long–Evans rats showed no effects of galanin on performance during training or probe trial. Wistar rats showed longer latencies to reach the hidden platform during training, and lack of selective quadrant search on the probe trial in response to galanin. Performance on the visible platform task and on locomotor activity in the open field was normal in rats treated with galanin. These results are consistent with an interpretation of strain differences in sensitivity to the inhibitory actions of galanin on learning and memory.

Characterization of the paradoxical growth hormone inhibitory effect of galanin in acromegaly.

Galanin is a 29-amino acid straight-chain biologically active peptide which has been found to decrease circulating GH levels in some acromegalic patients, whereas is able to increase GH secretion in normal subjects. The aim of our study was to ascertain the incidence, entity and mechanism of the paradoxical GH inhibitory effect of galanin in acromegaly also looking at possible correlations between the GH responses to galanin and the main clinical and biochemical features of the patients. Finally, the effects of either successful or unsuccessful neurosurgical intervention on the GH inhibitory effect of galanin in acromegaly were investigated. A series of 23 consecutive patients with active acromegaly seen at the Endocrine Section of the Department of Internal Medicine of the University of Brescia (Italy) between 1991 and 1994 was examined. The acromegalic patients were subdivided in group 1 (i.e. patients who were 1) untreated, 2) evaluated before surgery, and 3) not cured after surgery and radiotherapy) and group 2 (i.e. surgically cured). All patients were submitted at least once to the following biochemical and radiological evaluations: 1) baseline serum insulin-like growth factor-I and PRL samples, 2) iv infusion of synthetic porcine galanin (500 micrograms in 100 mL saline) from -10 to 30 min, 3) iv bolus injection of TRH (200 micrograms) at time zero, 4) oral glucose tolerance test (75 g glucose, orally) at time zero, and 5) magnetic resonance of the pituitary sella. Adenomatous tissue obtained during neurosurgery in four patients was cultured in vitro, and the effect of the addition of galanin in the culture medium on GH secretion was tested. During galanin infusion in 19 of 21 group 1 patients, serum GH levels were lower with respect to baseline (range of GH decrease, -6.2 to -85.4% with respect to basal levels). During galanin infusion, no reductions in GH levels were observed in the acromegalic patients cured after neurosurgery (group 2); on the contrary, 6 of 7 patients displayed a normal stimulatory response to galanin (range of GH increase, +120-1533.3% of the basal level). A significant correlation between the percent decrease in GH levels after galanin treatment and the percent increase after TRH was found in group 1 patients (r = -0.783; P < 0.05). In three of the four adenomas examined, galanin determined a clear decrease in GH secretion (mean nadir, 63.3 +/- 12% of the baseline secretion rate). In conclusion, we demonstrated that the large majority of numerous patients with active acromegaly show a decrease in serum GH levels after galanin administration.(ABSTRACT TRUNCATED AT 400 WORDS)

Chronic cerebroventricular galanin does not induce sustained hyperphagia or obesity

Acute central administration of galanin has been reported to increase fat consumption. These experiments were designed to test the hypothesis that repeated injections of galanin would elicit hyperphagia and weight gain and that this response would depend on the available diet. Male Sprague-Dawley rats were fed high (56% energy) or low (10% energy) fat diets. Galanin (300 pmol) or saline vehicle was injected into the third ventricle twice daily for 7 days and three times daily for another 6 days. On both the high-carbohydrate and high-fat diets, twice daily galanin increased daytime food intake, but there was a compensatory decrease in nighttime intake. The addition of a third, nighttime injection of galanin was ineffective in producing an increase in total 24-h intake. There was no significant increase in body weight during galanin treatment in rats eating either diet although animals eating the high-fat diet gained more weight as reflected by a significant increase in epididymal fat pad weight. Galanin treatment had no effects on serum insulin, glucose or corticosterone concentrations, measured at the end of the experiment. However, animals fed the high-fat diet had significantly higher insulin concentrations at the time of sacrifice. Although repeated central infusions of galanin reliably stimulated daytime intake of both diets, they failed to increase total daily energy intake or body weight.

Galanin antagonists block galanin-induced feeding in the hypothalamus and amygdala of the rat.

Galanin significantly increased food intake when microinjected into the region of the central nucleus of the amygdala as well as into the paraventricular nucleus of the hypothalamus. In the amygdala this effect was specific to feeding; no change in grooming, resting, or other behaviour was observed after galanin treatment. These results provide evidence that the amygdala may be an important site in the mediation of galanin-induced feeding. The galanin receptor antagonists, C7 and M40, antagonized galanin-induced feeding, while having no effect alone on food consumption in free-feeding rats. These new galanin receptor antagonists provide useful tools for further investigating the role of endogenous galanin in the regulation of feeding.

Effects of sex and age on the growth hormone response to galanin in healthy human subjects.

The aim of our study was to analyze the effects of sex and age on the GH response to galanin infusion in healthy subjects. We have studied 12 young (age, < 40 yr) nonobese healthy volunteers [6 females: age, 31.0 +/- 2.5 yr; body mass index (BMI), 21.6 +/- 0.9 kg/m2; 6 males: age, 29.2 +/- 1.4 yr; BMI, 23.3 +/- 0.4 kg/m2] and 11 old (age, > 65 yr) healthy subjects (5 females: age, 83.8 +/- 3.8 yr; BMI, 23.4 +/- 1.4 kg/m2; 6 males: age, 79.7 +/- 4.6 yr; BMI, 23.3 +/- 0.2 kg/m2). All subjects received an infusion of synthetic porcine galanin (500 micrograms, iv) in 100 mL saline from 0-45 min. Blood samples for GH measurement were drawn at -15, 0, 15, 30, 45, 60, 90, and 120 min. The GH peaks after galanin treatment in young females (11.9 +/- 2.9 micrograms/L) were significantly (P < 0.05) higher than those in the young males (5.1 +/- 1.8 micrograms/L). Old males showed significantly higher peak GH levels after galanin treatment (8.6 +/- 3.1 micrograms/L) than old females (2.4 +/- 0.6 micrograms/L). The GH peaks and areas under the curve after galanin treatment were significantly (P < 0.05) higher in young than in old females. On the contrary, no significant differences were observed after galanin treatment in young and old males. The magnitude of galanin-induced GH secretion significantly correlated with estradiol levels in young women. Our data seem to suggest that circulating estrogen levels play a crucial permissive role in galanin-induced GH secretion in humans.