Neuroscience
-
Type 2 diabetes mellitus (T2DM) is a major risk factor of a number of neurodegenerative diseases (NDDs). Ketogenic diet (KD) has significant beneficial effects on glycemic control and may act effectively against NDDs, but the mechanism remains unclear. In this study, we aimed to investigate the potential effects of KD on gene expressions in the brains of T2DM model mice. ⋯ Moreover, consistent with the gene set enrichment analysis results, proteasomal activity measured biochemically were enhanced in KD-fed T2DM mice. These data may facilitate the understanding of how KD can be protective to the brain in T2DM background. KD could be a new strategy for the prevention of NDDs in T2DM patients.
-
The brown rat (Rattus norvegicus) is known to show three types of behavioral responses to novel objects. Whereas some rats are indifferent to novel objects, neophobic and neophilic rats show avoidance and approach behavior, respectively. Here, we compared the dopaminergic, serotonergic, and noradrenergic systems immunohistochemically among these rats. ⋯ In the ventral tegmental area, Fos expression in dopaminergic neurons was higher in the neophilic rats than in the indifferent rats. These results demonstrate that approach/avoidance behavior to novel objects is correlated with the serotonergic and dopaminergic systems in the brown rat. We propose that the serotonergic system suppresses avoidance behavior while the dopaminergic system enhances approach behavior to novel objects.
-
Parkinson's disease (PD) is a common and complex neurodegenerative disease. This disease is typically characterized by the formation of Lewy bodies in multiple brain regions and dopaminergic neuronal loss in the substantia nigra pars compacta, resulting in non-motor symptoms (e.g., olfactory deficits) and motor dysfunction in the late stages. There is yet no effective cure for Parkinson's disease. ⋯ Finally, the activity of olfactory bulb neurons was improved and the loss of dopaminergic neurons in the substantia nigra pars compacta was reversed. Moreover, exosomes attenuated microglia and astrocyte activation, leading to a low level of inflammation in the brain. In conclusion, our study provided a new reference for the clinical application of exosomes in the treatment of PD.
-
Myeloid differentiation primary response gene 88 (MyD88), a downstream molecule directly linked to Toll-like receptor (TLRs) and IL1 receptor, has been implicated in ischemia-reperfusion injury across various organs. However, its role in cerebral ischemia-reperfusion injury (CIRI) remains unclear. Five transient middle cerebral artery occlusion (tMCAO) microarray datasets were obtained from the Gene Expression Omnibus (GEO) database. ⋯ Moreover, it attenuates the upregulation of inflammatory cytokines TNFα, IL17, and MMP9 while preserving the expression level of ZO1 after tMCAO, thereby safeguarding against blood-brain barrier (BBB) disruption. Finally, our findings suggest that MyD88 regulates the IRAK4/IRF5 signaling pathway associated with microglial activation. MyD88 participates in CIRI by regulating the inflammatory response and BBB damage following tMCAO.
-
Recent evidence has supported a pathogenic role for neuroinflammation in Parkinson's disease (PD). Inflammatory response has been associated with symptoms and subtypes of PD. However, it is unclear whether immune changes are involved in the initial pathogenesis of PD, leading to the non-motor symptoms (NMS) observed in its prodromal stage. ⋯ The striatum showed increased IL-17A, BDNF, and NFG levels compared to control mice. In conclusion, neuroinflammation may play an important role in the early stage of experimental PD-like syndrome, leading to cognitive and behavioral changes. Our results also indicate that intranasal administration of MPTP may represent a valuable mouse model for prodromal PD.