Neuroscience
-
Sushi repeat-containing protein X-linked 2 (SRPX2) is a novel hypothalamic protein and a ligand of the urokinase-type plasminogen activator receptor (uPAR), which is essential for proteolysis of extracellular matrix and tissue remodeling after an insult to the brain. However, little is known about regulation of SRPX2. Our objective was to investigate if SRPX2 expression is altered by (i) the deficiency of uPAR or uPA (urokinase-type plasminogen activator), and (ii) traumatic brain injury (TBI). ⋯ Unsupervised hierarchical clustering using SRPX2 expression did not identify genotype or injury-specific clusters. Our data demonstrate that SRPX2 expression in the hypothalamus is resistant to genetic deficiencies in the urokinase-system or to the hypothalamus-affecting TBI. The contribution of elevated Srpx2 gene expression in perilesional cortex to post-TBI recovery process, however, requires further exploration.
-
Temporal lobe epilepsy is triggered by an initial insult, such as status epilepticus, that initiates the process of epilepsy development. Heat shock protein 70 (Hsp70) is a ubiquitously expressed molecular chaperone, involved in the inflammatory response that is upregulated after status epilepticus. Hsp70 has been described as an endogenous intracellular ligand of Toll-like receptor 4. ⋯ No colocalization with the astrocytic marker GFAP or the microglia marker Iba1 was found. The intense neuronal Hsp70 upregulation during the early post-insult phase might contribute to the onset of excessive inflammation triggering molecular and cellular reorganization and generation of a hyperexcitable epileptic network. Therefore, development of multi-targeting strategies aiming at prevention of epileptogenesis should consider Hsp70 modulation in the early days following an epileptogenic insult.
-
Chronic cerebral hypoperfusion (CCH) is an important pathophysiological basis for AD and vascular cognitive impairment (VCI), but the underlying mechanisms are not completely clear. Age-related mitochondrial aging-like changes were closely associated with nervous system diseases and ischemia. This study aimed to observe the changes of cognitive function and hippocampal mitochondrial aging in rats with CCH. ⋯ CCH induced long-term spatial learning and memory deficits. The related alterations of mitochondrial aging and alpha-synuclein in the hippocampus are crucial for VCI pathogenesis.
-
Previous studies have focused on the effects of N-methyl-D-aspartate receptor (NMDAR) blockade on neonates, but little is known about the effect of the embryonic NMDAR blockade on offspring, especially the long-lasting effect, on behavior in adulthood. Here, pregnant rats at E14 were treated with ketamine for 5 successive days and undergone multiple behavior tests, electrophysiology experiment, and Western blotting analysis to detect the alterations in their offspring. We found that embryonic ketamine treatment induced anxiety-like behavior in adulthood (8-week old) offspring. ⋯ Moreover, at the 4-week time point, NMDA-evoked current was unchanged in PFC, but enhanced in hippocampal CA1 area, which may be caused by the over expression of NR2B in the hippocampus at 4-week time. Furthermore, NR2B knockdown, by using NR2B-shRNA lentivirus, in the hippocampal CA1 area at 3-4-week of age significantly rescued the decrease in NR2A expression in the PFC and anxiety-like behavior observed at 8-week adult offspring rats. In conclusion, our results suggested that embryonic ketamine treatment induced anxiety-like behavior and the downregulation of NMDAR function in PFC in the adulthood period of offspring, which might result from the enhanced function of NMDARs in the hippocampus at the 4-week juvenile time point.
-
In response to changes in brain micro-environment caused by aging, microglia could polarize into proinflammatory M1 phenotype and anti-inflammatory M2 phenotype. Besides, astroglia could polarize into A1 phenotype, exhibiting neurotoxicity, or A2 phenotype, showing neuroprotection. This study aimed to investigate the change of glial cells and dopaminergic (DA) neuron in midbrain with age. ⋯ Besides, M1 markers (TNF-α and IL-1β) increased and M2 markers (Arg1 and IL-10) decreased in aged rats. Furthermore, A2 markers (BDNF and GDNF) decreased and A1 markers (Lcn2 and C3) increased in aged rats. Age induced DA neuron loss and influenced midbrain glial cells phenotypic polarization, which might account for the occurrence and pathogenesis of Parkinson's diseases.