Neuroscience
-
Growth cone-mediated axonal outgrowth and accurate synaptic targeting are central to brain morphogenesis. Translocation of the growth cone necessitates mechanochemical regulation of cell-extracellular matrix interactions and the generation of propulsive traction forces onto the growth environment. However, the molecular mechanisms subserving force generation by growth cones remain poorly characterized. ⋯ Analysis of F-actin retrograde flow reveals that Fmn2 functions as a clutch molecule and mediates the coupling of the actin cytoskeleton to the growth substrate, via point contact adhesion complexes. Using traction force microscopy, we show that the Fmn2-mediated clutch function is necessary for the generation of traction stresses by neurons. Our findings suggest that Fmn2, a protein associated with neurodevelopmental and neurodegenerative disorders, is a key regulator of a molecular clutch activity and consequently motility of neuronal growth cones.
-
Our aim was to identify the longitudinal changes in gray matter volume (GMV) and secondary alterations of structural covariance after pontine stroke (PS). Structural MRI and behavioral scores were obtained at 1 week, 1 month, 3 months, 6 months in 11 patients with PS. Twenty healthy subjects underwent the same examination only once. ⋯ Based on the CBE Crus II_IL and CBE Crus I_CL as seed regions, structural covariance analysis revealed that there were more positively and negatively correlated brain regions in PS group, mainly distributed in the bilateral prefrontal lobe, parietal lobe, temporal lobe, paralimbic system and cerebellum. In addition, PS group showed more additional correlations between these covariant brain regions, and the changes of GMV in these regions were correlated with behavioral scores related to motor and cognitive functions. These findings indicate that PS could lead to significant GMV atrophy in the bilateral cerebellar posterior lobe at the early stage, accompanied by anomalous structural covariance patterns with more covariant brain regions and additional structural connectivity, which may provide useful information for understanding the neurobiological mechanisms of behavioral recovery after PS.
-
Effect of aging on daily rhythms of lactate metabolism in the medial prefrontal cortex of male mice.
Aging is associated with reduced amplitude and earlier timing of circadian (daily) rhythms in sleep, brain function, and behavior. We examined whether age-related circadian dysfunction extends to the metabolic function of the brain, particularly in the prefrontal cortex (PFC). Using enzymatic amperometric biosensors, we recorded lactate concentration changes in the PFC in Young (7 mos) and Aged (19 mos) freely-behaving C57BL/6N male mice. ⋯ Under constant conditions, the Aged rhythm showed a reduced amplitude not seen in the Young mice. We simultaneously observed a relationship between arousal state and PFC lactate rhythm via electroencephalography, which was modified by aging. Finally, using RT-qPCR, we found that aging affects the daily expression pattern of Glucose Transporter 1 (GLUT-1).
-
Neuropeptide S (NPS) is a recently discovered peptide signalling through its receptor NPSR, which is expressed throughout the brain. Since NPSR activation increases dopaminergic transmission, we now tested if NPSR modulates behavioural and neurochemical alterations displayed by an animal model of attention-deficit/hyperactivity disorder (ADHD), Spontaneous Hypertensive Rats (SHR), compared to its control strain, Wistar Kyoto rats (WKY). NPS (0.1 and 1 nmol, intracerebroventricularly (icv)) did not modify the performance in the open field test in both strains; however, NPSR antagonism with [tBu-d-Gly5]NPS (3 nmol, icv) increased, per se, the total distance travelled by WKY. ⋯ Immunoblotting of frontal cortical extracts showed no differences of NPSR density, although SHR had a lower NPS content than WKY. SHR showed higher activity of dopamine uptake than WKY, and NPS (1 nmol, icv) did not change this profile. Overall, the present work shows that the pattern of functioning of the NPS system is distinct in WKY and SHR, suggesting that this system may contribute to the pathophysiology of ADHD.
-
In the present study, we examined parvalbumin-immunoreactive cells and axons in the dentate gyrus of surgically resected tissues of therapy-resistant temporal lobe epilepsy (TLE) patients with different etiologies. Based on MRI results, five groups of patients were formed: (1) hippocampal sclerosis (HS), (2) malformation of cortical development, (3) malformation of cortical development + HS, (4) tumor-induced TLE, (5) patients with negative MRI result. Four control samples were also included in the study. ⋯ Significant correlation was found between the level of sprouting of axons and the ratio of ectopic/normally-located parvalbumin-containing cells. Electron microscopy demonstrated that sprouted parvalbumin-immunoreactive axons terminate on proximal and distal dendritic shafts as well as on dendritic spines of granule cells. Our results indicate alteration of target profile of parvalbumin-immunoreactive neurons in HS that contributes to the known synaptic remodeling in TLE.