Guoying Li

BACKGROUND: Little is known about the changes of brain structural and functional connectivity networks underlying the pathophysiology in migraine. We aimed to investigate how the cortical network reorganization is altered by frequent cortical overstimulation associated with migraine. METHODOLOGY/PRINCIPAL FINDINGS: Gray matter volumes and resting-state functional magnetic resonance imaging signal correlations were employed to construct structural and functional networks between brain regions in 43 female patients with migraine (PM) and 43 gender-matched healthy controls (HC) by using graph theory-based approaches. Compared with the HC group, the patients showed abnormal global topology in both structural and functional networks, characterized by higher mean clustering coefficients without significant change in the shortest absolute path length, which indicated that the PM lost optimal topological organization in their cortical networks. Brain hubs related to pain-processing revealed abnormal nodal centrality in both structural and functional networks, including the precentral gyrus, orbital part of the inferior frontal gyrus, parahippocampal gyrus, anterior cingulate gyrus, thalamus, temporal pole of the middle temporal gyrus and the inferior parietal gyrus. Negative correlations were found between migraine duration and regions with abnormal centrality. Furthermore, the dysfunctional connections in patients' cortical networks formed into a connected component and three dysregulated modules were identified involving pain-related information processing and motion-processing visual networks. CONCLUSIONS: Our results may reflect brain alteration dynamics resulting from migraine and suggest that long-term and high-frequency headache attacks may cause both structural and functional connectivity network reorganization. The disrupted information exchange between brain areas in migraine may be reshaped into a hierarchical modular structure progressively.

Alzheimer's disease (AD) is a progressive neurodegenerative disease characterized by accumulation of amyloid plaques and neurofibrillary tangles. Amyloid-β (Aβ) is widely recognized as a key factor in the pathogenesis of AD. Aβ1-42 a major component of amyloid plaques, has shown synaptotoxicity associated with impaired long-term potentiation and cognitive deficits. Alteration of neurogenesis in AD patients has been reported, while little is known about how Aβ1-42 affects hippocampal neurogenesis in the adult brain. In this study, we injected human Aβ1-42 peptide into hippocampal CA1 area of adult mouse brain bilaterally and evaluated histological change and neurogenesis in the hippocampus. Hematoxylin and eosin (HE) stain showed that Aβ1-42-injection resulted in an extensive neurodegeneration in the Aβ-accumulated area and CA3 in hippocampus. Immunostaining showed that intrahippocampal Aβ1-42-injection dramatically decreased the number of bromodeoxyuridine (BrdU)-positive cells in the dentate gyrus (DG) compared to the vehicle injection. Moreover, a significant decrease in the number of BrdU/double-cortin double-positive cells in Aβ1-42-injected hippocampus was observed, suggesting that Aβ1-42-injection inhibited progenitor cell proliferation and neurogenesis in subgranular zone of the DG in the adult brain. We also found that the Aβ1-42-mediated decline of neurogenesis was associated with decreased protein levels of cytokines interferon-γ (IFN-γ) and transcription factor nuclear factor-kappa B (NF-κB) in the hippocampus. These results suggest that Aβ1-42 inhibits hippocampal neurogenesis in the adult brain possibly through down-regulation of INF-γ and NF-κB signaling pathway. This study provides a new insight into Aβ1-42-mediated decrease in hippocampal neurogenesis in the adult central nervous system.

It has been reported that acrylamide can be detected in starchy food treated by high temperature (120 °C). People could be exposed to acrylamide in factory, laboratory, or even in daily life via diet and drinking water. Recently, the toxicity of acrylamide receives more attention. In addition to the neurotoxicity in humans, other toxic effects of acrylamide are worth further investigation. In this study, we investigated whether acrylamide affected the male reproductive system using high-performance liquid chromatography. In this study, the reproductive toxicity of acrylamide was observed in 3-week-old weaning male Sprague-Dawley rats treated with acrylamide at various doses (0, 5, 15 or 30 mg/kg/day). The results showed that food availability and reproductive organ indexes of the weaning male rats decreased. Levels of follicle-stimulating hormone and testosterone in serum increased while luteinizing hormone in serum decreased. The histopathological lesions and abnormal sperms presented in weaning rats after acrylamide treatment. The results suggested that there is a toxicological effect of acrylamide on the reproductive system of weaning male rats. Based on the findings above, we suggested that more attention should be paid to the toxicological study of acrylamide on weaning male rats or human beings, rather than just on adult male animals.

The mechanism underlying acrylamide-induced neurotoxicity remains controversial. Previous studies have focused on acrylamide-induced toxicity in adult rodents, but neurotoxicity in weaning rats has not been investigated. To explore the neurotoxic effect of acrylamide on the developing brain, weaning rats were gavaged with 0, 5, 15, and 30 mg/kg acrylamide for 4 consecutive weeks. No obvious neurotoxicity was observed in weaning rats in the low-dose acrylamide group (5 mg/kg). However, rats from the moderate- and high-dose acrylamide groups (15 and 30 mg/kg) had an abnormal gait. Furthermore, biochemical tests in these rats demonstrated that glutamate concentration was significantly reduced, and γ-aminobutyric acid content was significantly increased and was dependent on acrylamide dose. Immunohistochemical staining showed that in the cerebral cortex, γ-aminobutyric acid, glutamic acid decarboxylase and glial fibrillary acidic protein expression increased remarkably in the moderate- and high-dose acrylamide groups. These results indicate that in weaning rats, acrylamide is positively associated with neurotoxicity in a dose-dependent manner, which may correlate with upregulation of γ-aminobutyric acid and subsequent neuronal degeneration after the initial acrylamide exposure.