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Objective:To explore the effects of acute sleep fragmentation (SF) on cognitive function and the relationship between hippocampal Homer1a and synaptic plasticity in aged rats.Methods:One hundred and eight SPF grade male SD rats aged 22 to 24 months were divided into three groups according to random number table: control group (Control group), non-sleep fragmentation group (NSF group) and sleep fragmentation group (SF group), with 36 rats in each group.A sleep fragmentation model was established by sleep deprivation rod method.Morris water maze and novel object recognition tests were used to evaluate the learning and memory function of rats.Homer1a expression in hippocampus was detected by Western blot, and its distribution in CA1 area of hippocampus was observed by immunohistochemical staining.Golgi staining was used to observe the density of dendritic spines in CA1 area of hippocampus, and in vitro electrophysiological patch clamp test was used to detect the slope of field excitatory postsynaptic potential(fEPSP) from CA3 to CA1 in hippocampus.SPSS 22.0 and GraphPad Prism 9.3 softwares were used for data statistical analysis and mapping.One-way ANOVA was used for comparison among groups, and Tukey-Kramer test was used for further pairwise comparison. Results:(1)In the behavioral tests, there were statistical differences in the times of crossing the original platform, the target quadrant residence time and the new object recognition index at 1 h and 24 h among the three groups( F=13.63, 11.34, 21.26, 16.22, all P<0.01). The times of crossing the original platform in SF group((2.00±1.27) times) was lower than that of Control group ((5.67±2.16) times) and NSF group ((6.50±2.35) times) (both P<0.05). The target quadrant residence time in SF group ((9.02±4.84) s) was shorter than that in Control group ((24.73±7.37) s) and NSF group ((27.81±8.37)s) (both P<0.05). The new object recognition index at 1 h and 24 h in SF group were lower than those in Control group and NSF group (all P<0.05). (2) In Western blot assay, the expression of Homer1a protein in hippocampus of SF group(0.91±0.13) was higher than that of Control group(0.70±0.05) and NSF group(0.74±0.04)(both P<0.05). (3) In immunohistochemical staining, the optical density value of the Homer1a protein in CA1 area of hippocampus in the SF group was higher than that in the Control group and NSF group(both P<0.05). (4) In Golgi staining, the density of dendritic spines in CA1 area of hippocampus in SF group was lower than that in Control group and NSF group (both P<0.05). (5) In vitro electrophysiological test showed that the slope of fEPSP in CA3-CA1 area of hippocampus in SF group were lower than that in Control group and NSF group (both P<0.05). Conclusion:Acute SF intervention in aged rats can cause cognitive impairment, which may be associated with the inhibition of hippocampal synaptic plasticity induced by hippocampal Homer1a overexpression.
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A single infusion of ketamine has sustained antidepressant effects and significantly de-creases the risk of suicide,and the effects can last up for 7-10 days,but the underlying mechanism is un-clear. The mechanism was reviewed underlying the antidepressant effects of ketamine,and found that ket-amine may exert its antidepressant effect by regulating sleep/wake cycle,synaptic pruning,molecular path-ways,and neural circuits for treatment-refractory depression. Further studies are needed to investigate the ge-netic,molecular mechanisms underlying the sustained antidepressant effect of ketamine,and the associated imaging findings through in vivo imaging of animals and imaging genetics techniques,explore the optimal time for administration of ketamine,and then provide accurate scientific basis for enhancing its anti-depressant effect.
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Homer1a, encoded by immediate early genes (IEG), is a scaffold protein of post-synaptic density, which is widely expressed in the central nervous system. Homer1a overexpression has been found in many neuropsychiatric disorders, and its regulatory signal transduction plays an important role in synaptic plasticity and neuroprotection, which has gradually become a research focus. The research and development of the neuroprotective drugs targeting Homer1a has also attracted a great attention. In addition, studies in recent years have showed that the development and treatment of neurological diseases are correlated with the Homer1a level.This article reviews the basic structural characteristics of Homer1a, its protective effect on the schizophrenia, depression and epilepsy as well as the neuroprotective mechanism of Homer1a based on the latest research reports.
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(DBI) in rats by observation on the changes of Homer 1a expression and apoptotic nerve cells . Methods Spraque-Dawlley(SD) rats were randomly ( random number ) divided into control group and severe DBI group .DBI rat model was established according to the de-scription of Marmarou′s diffused brain injury .No injury was done on control group .The changes of neuron pathology were observed by light microscopy and electron microscope .The expression of Homer1a was observed by immunohistochemistry and western blot .The quan-tity of apoptotic cells was measured by terminal deoxynucleotidyl transfernase medicated nick end labeling ( TUNEL) method. Results The death rate of rats in severe DBI group was 49.3%.Compared with the control group , the ultrastructures in hippocampal neurons in-cluding organelle , axonal and capillary were damaged seriously after injury , the survival rate of nerve cells decreased significantly at 1 h after injury ([99.4 ±0.6]%vs [94.4 ±5.6]%, P<0.05), and peaked at 72 h ([99.2 ±0.8]%vs [54.7 ±33.8]%, P<0 .05) in DBI group.The expression of Homer1a protein increased significantly at 1 h after injury(0 .136 ±0.024 )and peaked at6 h(0.178 ± 0.028) and maintained to 24 h (0.176 ±0.027), while decreased at 48 h (0.145 ±0.02)and 72 h (0.117 ±0.012) in DBI group;the expression of Homer 1a was obviously higher at each time point in DBI group than that in control group (P <0.05).The apoptoticindex of TUNEL positive cells increased at 6 h and demonstrated significant difference at 72h in comparison to control group ([41.78 ±3 .96]%vs [1.92 ±0.22]%, P<0.05).The correlation analysis indicated that Homer1a expression from 1~24 h and 24 h~72 h was related to the survival rate of nerve cells ( r=-0.726, P<0.05; r=0.842, P<0.05) and the quantity of TUNE positive cells(r=0.738, P<0.0;5 r=-0.898, P<0.05). Conclusion The dynamic expression of Homer1a in hippocampus after severe DBI can reflect nerve cell loss.
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Objective To explore the effects of SB203580(a MAPK inhibitor) on the expression of Homer1a in hippocampus and learning-memory after diffuse brain injury in rats.Method Male Sprague-Dawlley rats were divided randomly into three groups:control group,diffuse brain injury(DBI) group and DBI+ SB203580 group (peritoneal injection,0.01 μg/kg).Morphological changes of neuronal cells were observed by electron microscope and the expression of Homer1a and phosphorylated p38MAPK was detected by immunohistochemistry and learning and memory functions were performed with Morris water maze (MWM).Results Compared with control group,ultrastructure of neuronal cells and synapses were significantly.The levels of phosphorylated p38MAPK(76.98±16.64,2.28±0.40,P＜0.05) and Homer1a (62.96± 12.74,1.28±0.10,P＜0.05)respectively were increased after injury impaired.MWM test showed that the escaping latency was prolonged((74.64± 8.96)s,(24.96±4.98)s,P＜0.05) and the frequency of crossing the platform was decreased(4.48± 1.12,12.65±2.36,P＜0.05).Compared with the model group,SB203580 decreased ultrastructure impariment in neuronal cells and synapses and decreased phosphorylated p38MAPK expression(54.82± 12.48,76.98± 16.64,P＜0.05) and increased Homer1a expression(54.82 ±12.48,76.98± 16.64,P＜0.05).MWM test showed that the escaping latency was shorten ((46.72±6.58) s,(74.64± 8.96) s,P＜0.05),and the frequency of crossing the platform was increased (7.56± 1.20,4.48± 1.12,P＜0.05).Conclusion SB203580 improves the learning-memory recovery after DBI,which is related to inhibition of p38MAPK activation and increasing Homer1a expression.
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BACKGROUND AND OBJECTIVES: Acute hypotension induces expression of c-Fos protein and phosphorylated extracellular signal-regulated kinase (pERK), and glutamate release in the vestibular nuclei. Expression of c-Fos protein and pERK is mediated by the excitatory neurotransmitter, glutamate. In this study, the signaling pathway of glutamate in the vestibular nuclei following acute hypotension was investigated. MATERIALS AND METHODS: Expression of metabotropic glutamate receptors (mGluRs) was measured by Western blotting in the medial vestibular nucleus following acute hypotension in rats. RESULTS: Expression of pGluR1 Ser831, a subtype of alpha-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA) receptors, peaked at 30 minutes after acute hypotension insult, and expression of pNR2B, a subtype of N-methyl-D-aspartate (NMDA) receptors, peaked at 2 hours after acute hypotension insult. Acute hypotension induced expression of Homer1a and group I mGluR in the medial vestibular nucleus. Expression of mGluR1 and mGluR5 peaked at 6 hours following acute hypotension insults. CONCLUSION: These results suggest that afferent signals from the peripheral vestibular receptors, resulting from acute hypotension insult, are transmitted through group I mGluRs as well as AMPA and NMDA receptors in the vestibular system.