Neuroscience
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GM1 gangliosides (GM1) are acidic glycosphingolipids that are present in cell membranes and lipid raft domains, being particularly abundant in central nervous systems. GM1 participate in modulating cell membrane properties, intercellular recognition, cell regulation, and signaling. We previously demonstrated that GM1 are expressed inside astrocytes but not on the cell surface. ⋯ Interestingly, this increase in GM1 expression induced the accumulation of autophagosomes in astrocytes. Moreover, the effect of haloperidol on the σ1R induced a decrease in GM1 in the cellular membrane of astrocytes. These findings suggested that the effects of haloperidol on the σ1R induced GM1 accumulation in the autophagosomes of astrocytes through activating the ERK pathway and a decrease in GM1 expression on the cell surface.
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Prematurity and hypoxia-ischemia (HI) can lead to movement disorders in infants. Considering that mild-moderate HI induced at postnatal day (PND) 3 has failed to produce motor disabilities similar to those seen in pre-term newborns, the main goal of the present study was to verify whether longer hypoxia periods would mimic motor function impairment, brain and muscle morphological alterations. Forty-nine Wistar rat pups of both sexes were randomly assigned to surgical control (CG) and HI groups. ⋯ Reduction in striatal volume correlates with behavioral assessment, HI-180' and HI-210' groups presented lower biceps brachii and tibialis anterior CSA. These results show that rats exposed to longer hypoxic periods at PND3 have encephalic and sensorimotor impairments that mimic those observed in preterm infants. Morphological changes in muscle tissue evidence a new pathophysiological characteristic of the HI model that might be of relevance for the study of sensorimotor deficits.
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Gambling Disorder (GD) is characterized by excessive gambling despite adverse consequences on individual functioning. In spite of some positive findings, it is difficult to draw any conclusion on the genetics of GD. Indeed, beyond DNA sequence variation, other regulatory mechanisms (like those that engage epigenetics) may explain gene alterations in this addictive disease. ⋯ The exposure to such operant task (compared to home-cage alone) modulated ventrostriatal but not prefrontal genes. A consistent increase of DNA methylation, in one specific CpG site at serotonin transporter gene, was evident in prefrontal cortex of "gambler" rats. Elucidation of epigenetic changes occurring during GD progression may pave the way to the development of new therapeutic strategies through specific modulation of epigenetic factors.
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Anoxic depolarization (AD) is an acute event evoked by brain ischemia, involving a profound loss of cell membrane potential and swelling that spreads over susceptible parts of the gray matter. Its occurrence is a strong predictor of the severity of neuronal injury. Little is known about this event in the Substantia Nigra, a midbrain nucleus critical for motor control. ⋯ The AD-resistance of the SNc involved smaller dysregulations of K(+) and Ca(2+) ions, and a slower loss of energy metabolites. Our results show that acute ischemia profoundly impairs the function and morphology of SNr neurons but not adjacent SNc neurons, and that the surprising higher tolerance of SNc neurons correlates with the resistance of the SNc region to AD. This differential response may affect the pattern of early neuronal injury that develops in the brainstem after acute ischemic insults.
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Parkinson's disease (PD) is the second most common neurodegenerative disease. It is generally believed that it is influenced by both genetic and environmental factors, but the precise pathogenesis of PD is unknown to date. In this study, we performed a pathway analysis based on genome-wide association study (GWAS) to detect risk pathways of PD in three GWAS datasets. ⋯ Five pathways had been reported to be PD-related pathways in the previous literature. Our findings also implied that there was a close association between immune response and PD. Continued investigation of these pathways will further help us explain the pathogenesis of PD.