| Background and AimsDepression is a common phychiatric disorder, has a high prevalence, high suicide rate,low cure rate, easy self-mutilation and other characteristics. Core symptoms of depressioninclude anhedonia, depressed mood, inappropriate guilt, feelings of hopelessness，usuallyaccompanied by cognitive function impaired, fatigue, weight/appetite disturbance, sleepdisturbance. Moreover, depressed patients are more likely to develop coronary arterydisease and type2diabetes. Depression also complicates the prognosis of other chronicmedical conditions. According to the world health organisation predicts that by2020depression will become the second major disease, second only to ischemic heart disease.Recently, depression is considered as a result from a complex interaction of geneticand environmental factors. Environmental factor plays a role just like a trigger. Stressevents are charactered by chronic, low-intensity, long-term presence, is the commonest predisposing factor of depression. Hippocampus is a vulnerable organ under stressconditions. The prefrontal cortex plays an important role in the integration of cognitiveand affective behavior. Both of them are participated in the development of depression.Galanin is a neuropeptide contains29amino acids (30amino acids in humans), widelydistributed in the central and peripheral nervous systems. Through interaction with threeG-protein-coupled receptors, galanin receptor1(GalR1), galanin receptor2(GalR2) andgalanin receptor3(GalR3), galanin has been implicated in numerous physiologicalfunctions. In the central nervous, galanin is co-existed with noradrenaline (NA) andserotonin (5-HT), and regulate the synthesis and release of them. As we all know，NA and5-HT are the major neurotransmissions participated in the pathogenesis of depressiondisorder. So we considered that galanin might be participated in the development ofdepression. The dorsal raphe nucleus is a main area of serotonergic neuron distributed, andit can send a source of pronounced projections to the hippocampus and the prefrontalcortex. The expression of galanin in the above-mentioned areas under depression stateremains unclear. There is no knowledge of galaninergic fibers in the dorsal raphe nucleuscould send projections to the hippocampus and the prefrontal cortex. That is a key factorto investigated whether galanin participate in the development of depression. In thepresent study, we establish an internationally recognized chronic mild unpredictable stressmodel of depression. Using the real time polymerase chain reaction combined withgalanin immuohistochemical techniques to monitored the expression of galanin and GalmRNA in the hippocampus and the prefrontal cortex. Then we used retrograde tracingcombined with galanin immunohistochemistry methods to determined whether exsited angalaninergic bidirectional pathways among the dorsal raphe nucleus, the dentate gyrus andthe prefrontal cortex.Methods:1. Established an internationally recognized chronic unpredictable mild stress model ofdepression. Using the open field test and sucrose preference test to detected thereliability of the depression model. Followed by real time polymerase chain reaction combined with galanin immuohistochemical technique to monitor the expression ofgalanin and Gal mRNA in the hippocampus and the prefrontal cortex.2. According to Paxis-Waston’s rat brain stereotaxic atlas to determined the coordinatesof the dorsal raphe nucleus, the prefrontal cortex and the hippocampus, respectively.After the retrograde tracer fluorogold injected into the coordinates of the points, weuse galanin immunohistochemistry method to observed whether Gal/FGdouble-labeled neurons have esisted in the dorsal raphe nucleus, the hippocampusand the prefrontal cortex.Results:1. FG was injected into the rostral part of the dorsal raphe nucleus, it is to see thatGal/FG double-labeled neurons were mainly distributed in the ipsilateral injectionpoints of the ventromedial prefrontal cortex, especially in prelimbic cortex andinfralimbic cortex.2. FG was injected into the mid-rostralcaudal part of the dorsal raphe nucleus, it is foundthat Gal/FG double-labeled neurons were equally distributed in the ipsilateral injectionpoints of the prefrontal cortex and the ventral part of the dentate gyrus.3. FG was injected into the caudal part of the dorsal raphe nucleus, it is found thatGal/FG double-labeled neurons were equally distributed in the ipsilateral injectionpoints of the prefrontal cortex and the dorsal part of the dentate gyrus.4. FG was injected into the ventral part of the prefrontal cortex, it is found that Gal/FGdouble-labeled neurons were mainly located in the ventral part of the dorsal raphenucleus, especially around the medial longitudinal fasciculus.5. FG was injected into the dorsal part of the prefrontal cortex, it is found that Gal/FGdouble-labeled neurons were mainly located in the ventral part of the dorsal raphenucleus.6. FG was injected into the dorsal part of the dentate gyrus, it is found that Gal/FGdouble-labeled neurons were mainly located in the dorsal part of the dorsal raphenucleus, closed to the periaqueductal gray. 7. FG was injected into the ventral apart of the dentate gyrus, it is found that Gal/FGdouble-labeled neurons were scattered in the ventral part of the dorsal raphe nucleus.8. Under the condition of chronic unpredictable mild stress, the expression of galanin andGal mRNA in the hippocampus were reduced, but there were no changes within theprefrontal cortex.Conclusions:1. Under the condition of chronic unpredictable mild stress, the expression of galanin andGal mRNA in the hippocampus were reduced, suggested that galanin might beinvolved in the development of depression.2. There are exsited an galaninergic bidirectional pathways among the dorsal raphenucleus, the dentate gyrus and the prefrontal cortex. Reciprocal connections among ofthem might play a cruial role in mood regulation and dysfunction of this loop mightlead to depression. |
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