During my digging I stumbled upon some studies discussing the effects of Galanin, and a novel peptide called Galanin Like Peptide (GALP). While this peptide and it’s receptors have been studied for some time, this is my first run-in with the info I’ve been uncovering. It looks like we may have a potentially exciting and interesting avenue to control food intake and mood disorders such as anxiety and depression.
Galanin is a neuropeptide that is widely expressed in the brain, spinal chord and gut of humans. The majority of Galanin’s effects are still a mystery waiting to be unfolded, but there is quite a bit of evidence pointing to its neuroprotective abilities, its notable effect on food intake and regulation of mood disorders.
Neurochem Res. 2012 Nov 30. [Epub ahead of print]
Novel Galanin Receptor Subtype Specific Ligand in Depression Like Behavior.
Saar I, Runesson J, Järv J, Kurrikoff K, Langel U.
Institute of Technology, University of Tartu, Tartu, Estonia, firstname.lastname@example.org.
Neuropeptide galanin and its three receptors, galanin receptor type 1-galanin receptor type 3, are known to be involved in the regulation of numerous psychological processes, including depression. Studies have suggested that stimulation of galanin receptor type 2 (GalR2) leads to attenuation of the depression-like behavior in animals. However, due to the lack of highly selective galanin subtype specific ligands the involvement of different receptors in depression-like behavior is yet not fully known. In the present study we introduce a novel GalR2 selective agonist and demonstrate its ability to produce actions consistent with theorized GalR2 functions and analogous to that of the anti-depressant, imipramine.
In the study quoted above we can see that there are three types of Galanin receptors, type 1, 2 and 3. It also appears to be that the type 2 receptor has the most beneficial impact on alleviating depressive behavior. Unfortunately, the researchers conclude that they have not yet developed or discovered a ligand that will bind selectively to the galanin type 2 receptor in order to verify their hypothesis.
Here’s an interesting study discussing Neuropeptide Y, another major player in the control of food intake, and Galanin. What’s unique about this article is that it discusses the effects of High Altitude on food intake, an inter-relation I had no idea existed until now.
Role of neuropeptide Y and galanin in high altitude induced anorexia in rats
Anorexia causing weight loss at high altitude (HA) is a major problem. Neuropeptide Y (NPY) and galanin are considered to have appetite regulatory function. The present study was therefore undertaken to investigate the changes in these two peptides at simulated HA and its possible role in anorexia. Male Sprague-Dawley rats (n = 8 in each group) were exposed to simulated HA (7620 m) for 1, 7, 14 and 21 days for 6 h a day and to an altitude of 6,096 m for 72 h to study the effect of intermittent and continuous exposure, respectively. NPY and galanin levels were estimated in different brain parts and plasma of exposed and unexposed control animals. Significant reduction in food intake was observed in rats during both intermittent as well as continuous exposure. In case of 72 h continuous exposure severe reduction in food intake was observed (73.2%) with reduction in body mass (approximately 29.7g/rat in 48h). Hypothalamic NPY levels were decreased by 54.7, 35.0 and 15.4% in 1, 7, and 14 days, respectively, in case of intermittent exposure to HA. However in case of 72 h HA exposure no significant change in hypothalamic and circulating NPY levels were observed. Plasma galanin levels were decreased in both intermittent and 72 h continuous HA exposed rats. Hypothalamic galanin levels were also decreased in 72h exposed rats. The changes in levels of these peptides may be responsible for anorexia at HA.
Singh SN, Vats P, Shyam R, Suri S, Kumria MM, Ranganathan S, Sridharan K, Selvamurthy W. Nutr Neurosci 2001;4(4):323-31
I am just as curious at this point, how they “Simulated” high altitude. Yikes.
But sure enough, high altitude did in fact lower both Neuropeptide Y and Galanin levels dramatically. If you were getting ready for a contest and you needed to reduce your appetite dramatically, then may I suggest a career in the Airline industry? Not very practical but interesting nonetheless.
So it appears that in the 90s there was a huge push to learn more about Galanin, not only because it seemed to effect food intake, but also affected reproduction (sex drive?).
Galanin/GALP and galanin receptors: role in central control of feeding, body weight/obesity and reproduction?
Scientific and commercial pharmacological interest in the role of galanin and galanin receptors in the regulation of food intake, energy balance, and obesity has waned recently, following initial enthusiasm during the 1980-1990s. It has been replaced by efforts to understand the role of newly discovered peptide systems such as the hypocretin/orexins, melanocortins and cocaine- and amphetamine-regulated transcript (CART) and their relationship to the important hormones, leptin and insulin. Thus, while numerous studies have revealed the ability of galanin to stimulate food intake via actions at sites within the hypothalamus, and shown reliable changes in hypothalamic galanin synthesis in response to food ingestion; findings including the lack of a ‘body weight/obesity’ phenotype in galanin transgenic mouse strains and a lack of agonists/antagonists for galanin receptor subtypes have probably served to reduce enthusiasm. However, as more is learnt about the general and galanin-related neurochemistry of brain pathways involved in feeding, metabolism and body weight control, the potential importance of galanin systems is again in focus. Studies of the newly discovered galanin family peptide, ‘galanin-like peptide’ (GALP), highlight the likely role of galanin peptides and receptors in the physiological coupling of body weight, adiposity and reproductive function. GALP is produced by a discrete population of neurons within the basomedial arcuate nucleus (and median eminence) that send projections to the anterior paraventricular nucleus and that make close contacts with leutinizing hormone-releasing hormone (LHRH) neurons in basal forebrain. Furthermore, GALP neurons express leptin receptors and respond to leptin treatment by increasing their expression of GALP mRNA. Centrally administered GALP activates LHRH-immunoreactive neurons and increases plasma LH levels. These findings suggest a direct stimulatory action of endogenous GALP on gonadotropin secretion via actions within the hypothalamus/basal forebrain, with leptin actions linking this system to body adipose levels.
Gundlach AL. Galanin/GALP and galanin receptors: role in central control of feeding, body weight/obesity and reproduction? Eur J Pharmacol 2002 Apr 12;440(2-3):255-68
So it appears that Galanin increases LH, and positively modulates Leptin, which is of course a major player in food intake. It’s important to point out that both Leptin and Galanin, while being very important in food intake and reproduction, are not simply the kinds of peptides that you just increase and get a positive result. Leptin studies have been done and we see that a good majority of overweight people have very high levels of Leptin in spite of the fact that Leptin should lower food intake. To me, this points to an issue of sensitivity. At some point in time, overeating begins to decrease sensitivity to Leptin.
So how do we try and modulate this system? I’m not sure yet. There is evidence that shows herbal adaptogens have an impact on things like Neuropeptide-Y, and I think I will uncover studies showing a connection, or we will find new research emerging showing an effect. The trouble here is the specificity of it all. When you talk about these types of peptides, you are talking about a really selective and delicate system. And as we’ve seen with Leptin, it’s not always a matter of “More is Better.”