Search

Background: Major depressive disorder is a common comorbidity in migraineurs. Depression may affect the progression and prognosis of migraine. Few studies have examined the brain function in migraineurs that may cause this comorbidity. Here, we aimed to explore depression-related abnormalities in the intrinsic brain activity of interictal migraineurs with comorbid depression using resting-state functional magnetic resonance imaging., Results: Significant main effects of migraine and depression provided evidence that migraine and depression jointly affected the left medial prefrontal cortex, which was thought to be the neural basis of self-referential mental activity in previous studies. Abnormalities in this region may contribute to determining the common symptoms of migraine and depression and even result in comorbidity. Additionally, migraineurs with comorbid depression had different developmental trajectories in the right thalamus and fusiform, which were associated with recognizing, transmitting, controlling and remembering pain and emotion., Conclusions: Based on our findings, the abnormal mPFC which may contribute to determining the common symptoms in migraine and depression and may be a therapeutic target for migraineurs comorbid depression. The different developmental trajectory in thalamus and fusiform indicates that the comorbidity may arise through a specific mechanism rather than simple superposition of migraine and depression.

Background: Most migraineurs develop cutaneous allodynia (CA) during migraine, and the underlying mechanism of CA in migraine is thought to be sensitization of the third-order trigeminovascular neurons in the posterior thalamic nuclei. This study aimed to investigate whether the ascending/descending pathway associated with the thalamus is disturbed in migraineurs with CA (MWCA) using effective connectivity analysis of resting-state functional magnetic resonance imaging., Methods: Thirty four migraineurs without aura (14 MWCA and 20 migraineurs without CA (MWoCA)) and 25 matched healthy controls (HC) were recruited in the study. The effective connectivity pathways associated with the posterior thalamus (PTH) were investigated using the Granger causality analysis. We chose bilateral PTH as two individual seeds, and compared MWCA with MWoCA and HC, respectively. Spearman correlation analysis was performed to test the correlation between the abnormal effective connectivity and the allodynia severity of MWCA., Results: Compared with MWoCA, MWCA showed decreased inflows from the left limbic regions and dorsal medial prefrontal cortex (dmPFC) to the ipsilateral PTH, as well as increased inflow from the right ventral medial prefrontal cortex (vmPFC) to the ipsilateral PTH; no significantly different outflows from the bilateral PTH to other regions were found. Compared with HC, MWCA showed increased outflows from the left PTH to the bilateral vmPFC, decreased outflows from the right PTH to the bilateral temporoparietal areas, decreased inflow from the left parietooccipital area to the ipsilateral PTH, and increased inflows from the right dorsolateral prefrontal cortex and the bilateral temporoparietal areas to the right PTH. Correlation analyses revealed that the disturbed connectivities between PTH and cuneus, as well as PTH and middle frontal gyrus were associated with the allodynia severity of MWCA., Conclusions: MWCA demonstrated disrupted effective connection pathways between the PTH and other cortical or subcortical regions that participated in multi-dimentional pain processing. Our findings highlight the dysfunctional ascending and descending pain network at the thalamic-level and may help to illuminate the possible pathophysiologic mechanisms of CA.

Germ line mutations in breast cancer gene 1 (BRCA1) predispose women to breast and ovarian cancers. Although BRCA1 is involved in many important biological processes, the function of BRCA1 in homologous recombination (HR) mediated repair is considered one of the major mechanisms contributing to its tumor suppression activity, and the cause of hypersensitivity to poly(ADP-ribose) polymerase (PARP) inhibitors when BRCA1 is defective. Mounting evidence suggests that the mechanism of repairing DNA double strand breaks (DSBs) by HR is different than the mechanism operating when DNA replication is blocked. Although BRCA1 has been recognized as a central component in HR, the precise role of BRCA1 in HR, particularly under replication stress, has remained largely unknown. Given the fact that DNA lesions caused by replication blockages are the primary substrates for HR in mitotic cells, functional analysis of BRCA1 in HR repair in the context of replication stress should benefit our understanding of the molecular mechanisms underlying tumorigenesis associated with BRCA1 deficiencies, as well as the development of therapeutic approaches for cancer patients carrying BRCA1 mutations or reduced BRCA1 expression. This review focuses on the current advances in this setting and also discusses the significance in tumorigenesis and cancer therapy.