The Dawn and Advancement of the Knowledge of the Genetics of Migraine.

Background: Migraine is a prevalent episodic brain disorder known for recurrent attacks of unilateral headaches, accompanied by complaints of photophobia, phonophobia, nausea, and vomiting. Two main categories of migraine are migraine with aura (MA) and migraine without aura (MO). Main body: Early twin and population studies have shown a genetic basis for these disorders, and efforts have been invested since to discern the genes involved. Many techniques, including candidate-gene association studies, loci linkage studies, genome-wide association, and transcription studies, have been used for this goal. As a result, several genes were pinned with concurrent and conflicting data among studies. It is important to understand the evolution of techniques and their findings. Conclusions: This review provides a chronological understanding of the different techniques used from the dawn of migraine genetic investigations and the genes linked with the migraine subtypes.

Ventral tegmental area inactivation suppresses the expression of CA1 long term potentiation in anesthetized rat.

The hippocampus receives dopaminergic projections from the ventral tegmental area (VTA). Modulatory effect of dopamine on hippocampal long term potentiation (LTP) has been studied before, but there are conflicting results and some limitations in previous reports. Most of these studies show a significant effect of dopamine on the late phase of LTP in CA1 area of the hippocampus, while few reports show an effect on the early phase. Moreover, they generally manipulated dopamine receptors in the hippocampus and there are few studies investigating influence of the VTA neural activity on hippocampal LTP in the intact brain. Besides, VTA neurons contain other neurotransmitters such as glutamate and GABA that may modify the net effect of dopamine. In this study we examined the effect of VTA reversible inactivation on the induction and maintenance of early LTP in the CA1 area of anesthetized rats, and also on different phases of learning of a passive avoidance (PA) task. We found that inactivation of the VTA by lidocaine had no effect on CA1 LTP induction and paired-pulse facilitation, but its inactivation immediately after tetanic stimulation transiently suppressed the expression of LTP. Blockade of the VTA 20 min after tetanic stimulation had no effect on the magnitude of LTP. Moreover, VTA inactivation immediately after training impaired memory in the passive avoidance task, while its blockade before or 20 min after training produced no memory deficit. It can be concluded that VTA activity has no effect on CA1 LTP induction and acquisition of PA task, but involves in the expression of LTP and PA memory consolidation.

Effect of reversible inactivation of reuniens nucleus on memory processing in passive avoidance task.

The reuniens nucleus (RE) is the largest nucleus of the midline thalamic nuclei (MLN). RE has strongly connections with the amygdala and hippocampus, the structures that are involved in the learning and memory processes. In our previous report we have shown the role of RE in the spatial learning and memory using Morris water maze (MWM) task. Since RE is connected to multiple limbic structures, its involvement in the emotional learning and memory is a possibility. The present study was designed to elucidate the role of RE in acquisition, consolidation, and retrieval on the passive avoidance (PA) task which depends on a distributed network including the thalamus, amygdala, medial prefrontal cortex (mPFC) and hippocampus. For this purpose, rats were chronically implanted with a cannula aimed at the RE through which 0.5 µl tetracaine (2%) or saline were injected. Rats were trained in a PA task and their retention test was performed 24h later. The injection of saline or tetracaine was applied 5 min before or 5, 90, and 360 min after the acquisition trial and 5 min before the retention tests. Our findings showed that inactivation of RE before training did not affect acquisition, but affected memory retention 24h later in PA task. Moreover, inactivation of RE only 5 min after training impaired consolidation but not after 90 or 360 min. Also, inactivation of the RE, 5 min before the retrieval test impaired memory retrieval in PA task. In conclusion, it seems that RE is involved in memory processes in rats.

Orexin-1 receptor mediates long-term potentiation in the dentate gyrus area of freely moving rats.

Orexin neurons, localized in the lateral hypothalamus area, synthesize two neuropeptides called orexin A and orexin B and send their axons to hippocampal formation including dentate gyrus (DG). Orexin A and orexin B act as endogenous ligands for two G-protein coupled receptors called orexin-1 and orexin-2 receptors (OX1R and OX2R). In the dentate gyrus (DG) region, OX1R, which has high affinity for orexin A, is expressed. Conflicting results have been reported regarding the effect of orexinergic system on synaptic plasticity. When given alone, SB-334867-A, a non-peptide OX1R antagonist, is a suitable drug to assess the natural and physiological significance of endogenous orexins. In the present research, we studied the effects of DG-OX1Rs antagonization on long-term potentiation (LTP) using two different high frequency stimulation (HFS) protocols i.e. 200 and 400 Hz in freely moving rats. The results showed that inactivation of DG-OX1Rs impair LTP induction in both HFS protocols which lasts beyond 24 h. This occurs with respect to both the population excitatory post-synaptic potential slope and population spike amplitude. Our findings suggest that endogenous orexins are involved in the expression of LTP, at least through DG-OX1Rs.

Comparison of fatty acid profiles of aorta and internal mammary arteries in patients with coronary artery disease.

BACKGROUND: Atherosclerosis represents the principal cause of death in the many societies. Since few data have been published about the composition of fatty acids in atherosclerotic arteries such as the aorta comparing to the non affected internal mammary artery which is used for aortocoronary bypass grafting, we compared the fatty acid profiles of atherosclerotic aorta and internal mammary arteries in human individuals. METHODS: Twenty-one angiographically documented coronary artery disease (CAD) patients who were admitted to the open heart surgery division enrolled in this study. They were operated electively for coronary artery bypass grafting surgery (CABG). Small segments of ascending aorta and internal mammary arteries were sampled during open heart surgery. The samples were subjected to lipid extraction and fatty acid analysis by high performance liquid chromatography. RESULTS: The results showed that different fatty acid profiles were seen in the aorta and internal mammary arteries. The atherosclerotic aorta contained lower amounts of unsaturated fatty acids (including trans isomer of oleic acid) and higher proportions of saturated fats comparing to the internal mammary. In the aorta also, the amounts of omega6 series of fatty acids were more and levels of omega3 fats were less than the internal mammary. CONCLUSION: This study suggests that modification of fatty acids may play a role during atherogenesis.