Microglia-mediated calcium-permeable AMPAR accumulation in the nucleus accumbens drives hyperlocomotion during cocaine withdrawal.

During withdrawal from cocaine, calcium permeable-AMPA receptors (CP-AMPAR) progressively accumulate in nucleus accumbens (NAc) synapses, a phenomenon linked to behavioral sensitization and drug-seeking. Recently, it has been suggested that neuroimmune alterations might promote aberrant changes in synaptic plasticity, thus contributing to substance abuse-related behaviors. Here, we investigated the role of microglia in NAc neuroadaptations after withdrawal from cocaine-induced conditioned place preference (CPP). We depleted microglia using PLX5622-supplemented diet during cocaine withdrawal, and after the place preference test, we measured dendritic spine density and the presence of CP-AMPAR in the NAc shell. Microglia depletion prevented cocaine-induced changes in dendritic spines and CP-AMPAR accumulation. Furthermore, microglia depletion prevented conditioned hyperlocomotion without affecting drug-context associative memory. Microglia displayed fewer number of branches, resulting in a reduced arborization area and microglia control domain at late withdrawal. Our results suggest that microglia are necessary for the synaptic adaptations in NAc synapses during cocaine withdrawal and therefore represent a promising therapeutic target for relapse prevention.

Thalamic Foxp2 regulates output connectivity and sensory-motor impairments in a model of Huntington's Disease.

BACKGROUND: Huntington's Disease (HD) is a disorder that affects body movements. Altered glutamatergic innervation of the striatum is a major hallmark of the disease. Approximately 30% of those glutamatergic inputs come from thalamic nuclei. Foxp2 is a transcription factor involved in cell differentiation and reported low in patients with HD. However, the role of the Foxp2 in the thalamus in HD remains unexplored. METHODS: We used two different mouse models of HD, the R6/1 and the HdhQ111 mice, to demonstrate a consistent thalamic Foxp2 reduction in the context of HD. We used in vivo electrophysiological recordings, microdialysis in behaving mice and rabies virus-based monosynaptic tracing to study thalamo-striatal and thalamo-cortical synaptic connectivity in R6/1 mice. Micro-structural synaptic plasticity was also evaluated in the striatum and cortex of R6/1 mice. We over-expressed Foxp2 in the thalamus of R6/1 mice or reduced Foxp2 in the thalamus of wild type mice to evaluate its role in sensory and motor skills deficiencies, as well as thalamo-striatal and thalamo-cortical connectivity in such mouse models. RESULTS: Here, we demonstrate in a HD mouse model a clear and early thalamo-striatal aberrant connectivity associated with a reduction of thalamic Foxp2 levels. Recovering thalamic Foxp2 levels in the mouse rescued motor coordination and sensory skills concomitant with an amelioration of neuropathological features and with a repair of the structural and functional connectivity through a restoration of neurotransmitter release. In addition, reduction of thalamic Foxp2 levels in wild type mice induced HD-like phenotypes. CONCLUSIONS: In conclusion, we show that a novel identified thalamic Foxp2 dysregulation alters basal ganglia circuits implicated in the pathophysiology of HD.

Acupuncture Improves Synaptic Plasticity of SAMP8 Mice through the RhoA/ROCK Pathway.

BACKGROUND: Studies have found synaptic plasticity damage to be an early marker of Alzheimer's disease (AD). RhoA/ROCK pathway is involved in the regulation of synaptic plasticity. Acupuncture can significantly improve the cognitive state of AD. OBJECTIVE: We aimed to use modern biological technology to detect the changes in synaptic plasticity and RhoA/ROCK pathway in SAMP8 mice, as well as the intervention effect of acupuncture. METHODS: Morris water maze and electrophysiological techniques were used in vivo to detect the changes in spatial memory and LTP of mice. Golgi Cox staining and CASEVIEWER2.1 software were used to quantitatively analyze the changes in the morphology and number of dendritic spines in the hippocampus of mice. The activity of RhoA and ROCK2 in the hippocampus of mice was detected, respectively, by pull-down technique and ELISA. WB technique was used to detect the protein expression of ROCK2 and phosphorylation level of MLC2, LIMK2, and CRMP2 in the hippocampus of mice. RESULTS: The neurobehavior and synaptic plasticity of 8-month-old SAMP8 mice were found to be significantly impaired. Acupuncture could improve the spatial learning and memory ability of SAMP8 mice, and partially prevent the reduction in the number of spines on the secondary branches of the apical dendrites in the hippocampus and the attenuation of LTP. The RhoA/ROCK pathway was significantly activated in the hippocampus of 8-month-old SAMP8 mice, and acupuncture had an inhibitory effect on it. CONCLUSION: Acupuncture can improve synaptic plasticity by inhibiting the abnormal activation of the RhoA/ROCK pathway, and improve the spatial learning and memory ability of AD, so as to achieve the purpose of treating AD.

Anti-Hebbian plasticity in the motor cortex promotes defensive freezing.

Regional brain activity often decreases from baseline levels in response to external events, but how neurons develop such negative responses is unclear. To study this, we leveraged the negative response that develops in the primary motor cortex (M1) after classical fear learning. We trained mice with a fear conditioning paradigm while imaging their brains with standard two-photon microscopy. This enabled monitoring changes in neuronal responses to the tone with synaptic resolution through learning. We found that M1 layer 5 pyramidal neurons (L5 PNs) developed negative tone responses within an hour after conditioning, which depended on the weakening of their dendritic spines that were active during training. Blocking this form of anti-Hebbian plasticity using an optogenetic manipulation of CaMKII activity disrupted negative tone responses and freezing. Therefore, reducing the strength of spines active at the time of memory encoding leads to negative responses of L5 PNs. In turn, these negative responses curb M1's capacity for promoting movement, thereby aiding freezing. Collectively, this work provides a mechanistic understanding of how area-specific negative responses to behaviorally relevant cues can be achieved.

SNS alleviates depression-like behaviors in CUMS mice by regluating dendritic spines via NCOA4-mediated ferritinophagy.

ETHNOPHARMACOLOGICAL RELEVANCE: Depression is one of the most common mood disturbances worldwide. The Si-ni-san formula (SNS) is a famous classic Traditional Chinese Medicine (TCM) widely used to treat depression for thousands of years in clinics. However, the mechanism underlying the therapeutic effect of SNS in improving depression-like behaviors following chronic unpredictable mild stress (CUMS) remains unknown. AIM OF THE STUDY: This study aimed to investigate whether SNS alleviates depression-like behaviors in CUMS mice by regulating dendritic spines via NCOA4-mediated ferritinophagy in vitro and in vivo. STUDY DESIGN AND METHODS: In vivo, mice were exposed to CUMS for 42 days, and SNS (4.9, 9.8, 19.6 g/kg/d), fluoxetine (10 mg/kg/d), 3-methyladenine (3-MA) (30 mg/kg/d), rapamycin(1 mg/kg/d), and deferoxamine (DFO) (200 mg/kg/d) were conducted once daily during the last 3 weeks of the CUMS procedure. In vitro, a depressive model was established by culture of SH-SY5Y cells with corticosterone, followed by treatment with different concentrations of freeze-dried SNS (0.001, 0.01, 0.1 mg/mL) and rapamycin (10 nM), NCOA4-overexpression, Si-NCOA4. After the behavioral test (open-field test (OFT), sucrose preference test (SPT), forced swimming test (FST) and tail suspension test (TST), dendritic spines, GluR2 protein expression, iron concentration, and ferritinophagy-related protein levels (P62, FTH, NCOA4, LC3-II/LC3-I) were tested in vitro and in vivo using immunohistochemistry, golgi staining, immunofluorescence, and Western blot assays. Finally, HEK-293T cells were transfected by si-NCOA4 or GluR2-and NCOA4-overexpression plasmid and treated with corticosterone(100 µM), freeze-dried SNS(0.01 mg/mL), rapamycin(25 nM), and 3-MA(5 mM). The binding amount of GluR2, NCOA4, and LC3 was assessed by the co-immunoprecipitation (CO-IP) assay. RESULTS: 3-MA, SNS, and DFO promoted depressive-like behaviors in CUMS mice during OFT, SPT, FST and TST, improved the amount of the total, thin, mushroom spine density and enhanced GluR2 protein expression in the hippocampus. Meanwhile, treatment with SNS decreased iron concentrations and inhibited NCOA4-mediated ferritinophagy activation in vitro and in vivo. Importantly, 3-MA and SNS could prevent the binding of GluR2, NCOA4 and LC3 in corticosterone-treated HEK-293T, and rapamycin reversed this phenomenon after treatment with SNS. CONCLUSION: SNS alleviates depression-like behaviors in CUMS mice by regulating dendritic spines via NCOA4-mediated ferritinophagy.

Neurotrophic fragments as therapeutic alternatives to ameliorate brain aging.

Aging is a global phenomenon and a complex biological process of all living beings that introduces various changes. During this physiological process, the brain is the most affected organ due to changes in its structural and chemical functions, such as changes in plasticity and decrease in the number, diameter, length, and branching of dendrites and dendritic spines. Likewise, it presents a great reduction in volume resulting from the contraction of the gray matter. Consequently, aging can affect not only cognitive functions, including learning and memory, but also the quality of life of older people. As a result of the phenomena, various molecules with notable neuroprotective capacity have been proposed, which provide a therapeutic alternative for people under conditions of aging or some neurodegenerative diseases. It is important to indicate that in recent years the use of molecules with neurotrophic activity has shown interesting results when evaluated in in vivo models. This review aims to describe the neurotrophic potential of molecules such as resveratrol (3,5,4'-trihydroxystilbene), neurotrophins (brain-derived neurotrophic factor), and neurotrophic-type compounds such as the terminal carboxyl domain of the heavy chain of tetanus toxin, cerebrolysin, neuropeptide-12, and rapamycin. Most of these molecules have been evaluated by our research group. Studies suggest that these molecules exert an important therapeutic potential, restoring brain function in aging conditions or models of neurodegenerative diseases. Hence, our interest is in describing the current scientific evidence that supports the therapeutic potential of these molecules with active neurotrophic.

Impact of Pharmacological and Non-Pharmacological Modulators on Dendritic Spines Structure and Functions in Brain.

Dendritic spines are small, thin, hair-like protrusions found on the dendritic processes of neurons. They serve as independent compartments providing large amplitudes of Ca2+ signals to achieve synaptic plasticity, provide sites for newer synapses, facilitate learning and memory. One of the common and severe complication of neurodegenerative disease is cognitive impairment, which is said to be closely associated with spine pathologies viz., decreased in spine density, spine length, spine volume, spine size etc. Many treatments targeting neurological diseases have shown to improve the spine structure and distribution. However, concise data on the various modulators of dendritic spines are imperative and a need of the hour. Hence, in this review we made an attempt to consolidate the effects of various pharmacological (cholinergic, glutamatergic, GABAergic, serotonergic, adrenergic, and dopaminergic agents) and non-pharmacological modulators (dietary interventions, enriched environment, yoga and meditation) on dendritic spines structure and functions. These data suggest that both the pharmacological and non-pharmacological modulators produced significant improvement in dendritic spine structure and functions and in turn reversing the pathologies underlying neurodegeneration. Intriguingly, the non-pharmacological approaches have shown to improve intellectual performances both in preclinical and clinical platforms, but still more technology-based evidence needs to be studied. Thus, we conclude that a combination of pharmacological and non-pharmacological intervention may restore cognitive performance synergistically via improving dendritic spine number and functions in various neurological disorders.

Evaluation of microglia in a rodent model of Parkinson's disease primed with L-DOPA after sub-anesthetic ketamine treatment.

Parkinson's disease (PD) is a neurodegenerative disease caused by the death of dopaminergic neurons in the substantia nigra pars compacta (SNpc), characterized by motor dysfunction. While PD symptoms are well treated with L-DOPA, continuous use can cause L-DOPA-induced dyskinesia (LID). We have previously demonstrated that sub-anesthetic ketamine attenuated LID development in rodents, measured by abnormal involuntary movements (AIMs), and reduced the density of maladaptive striatal dendritic mushroom spines. Microglia may play a role by phagocytosing maladaptive neuronal spines. In this exploratory study, we hypothesized that ketamine would prevent AIMs and change microglia ramified morphology - an indicator of a microglia response. Unilaterally 6-hydroxydopamine (6-OHDA)-lesioned rats were primed with daily injections of L-DOPA for 14 days, treated on days 0 and 7 for 10-hours with sub-anesthetic ketamine (i.p.), and we replicated that this attenuated LID development. We further extended our prior work by showing that while ketamine treatment did lead to an increase of striatal interleukin-6 in dyskinetic rats, indicating a modulation of an inflammatory response, it did not change microglia number or morphology in the dyskinetic striatum. Yet an increase of CD68 in the SNpc of 6-OHDA-lesioned hemispheres post-ketamine indicates increased microglia phagocytosis suggestive of a lingering microglial response to 6-OHDA injury in the SNpc pointing to possible anti-inflammatory action in the PD model in addition to anti-dyskinetic action. In conclusion, we provide further support for sub-anesthetic ketamine treatment of LID. The mechanisms of action for ketamine, specifically related to inflammation and microglia phagocytic functions, are emerging, and require further examination.

Prenatal treatment with rapamycin restores enhanced hippocampal mGluR-LTD and mushroom spine size in a Down's syndrome mouse model.

Down syndrome (DS) is the most frequent genetic cause of intellectual disability including hippocampal-dependent memory deficits. We have previously reported hippocampal mTOR (mammalian target of rapamycin) hyperactivation, and related plasticity as well as memory deficits in Ts1Cje mice, a DS experimental model. Here we characterize the proteome of hippocampal synaptoneurosomes (SNs) from these mice, and found a predicted alteration of synaptic plasticity pathways, including long term depression (LTD). Accordingly, mGluR-LTD (metabotropic Glutamate Receptor-LTD) is enhanced in the hippocampus of Ts1Cje mice and this is correlated with an increased proportion of a particular category of mushroom spines in hippocampal pyramidal neurons. Remarkably, prenatal treatment of these mice with rapamycin has a positive pharmacological effect on both phenotypes, supporting the therapeutic potential of rapamycin/rapalogs for DS intellectual disability.

[Effect of Baihe Dihuang Decoction on synaptic plasticity of hippocampus in rats with anxious depression].

To explore the effect of Baihe Dihuang Decoction on the synaptic plasticity of hippocampal neurons in rats with anxious depression. Fifty SD rats were randomly divided into normal group, model group, venlafaxine group(6.75 mg·kg~(-1)), high-dose Baihe Dihuang Decoction group(8.64 g·kg~(-1)) and low-dose Baihe Dihuang Decoction group(4.32 g·kg~(-1)). Chronic restraint stress(6 h) combined with corticosterone(ih, 30 mg·kg~(-1)) was used to establish an anxious depression model, and 7 days after modeling, the administration started and continued for 21 days. The anxiety and depression-like behaviors of the rats were evaluated. Golgi-Cox staining and electron microscopy were used to observe the morphology and ultrastructural changes of synaptic dendrites. Immunofluorescence was used to detect the expression of hippocampal synaptic plasticity protein synapsin-1 and postsynaptic density protein 95(PSD-95). Western blot method was used to detect the expression of functional protein synaptophysin(SYP) and synaptic Ras GTPase activating protein(SynGap). The results showed that the rats in the model group had obvious anxiety and depression-like behaviors, the hip-pocampal dendritic spine density and branch length were reduced, the number of synapses was cut, and the internal structure was da-maged. The average fluorescence intensity of synapsin-1 and PSD-95 was significantly reduced and the expression of SYP and SynGap also decreased. High-dose Baihe Dihuang Decoction could significantly improve the anxiety and depression-like behaviors of model rats, relieve synaptic damage, and increase the expression of synapsin-1, PSD-95, SYP, and SynGap proteins. Therefore, we believe that Baihe Dihuang Decoction can improve anxiety and depression behaviors by regulating the synaptic plasticity of hippocampal neurons.

Ghrelin treatment leads to dendritic spine remodeling in hippocampal neurons and increases the expression of specific BDNF-mRNA species.

Ghrelin (Gr) is an orexigenic peptide that acts via its specific receptor, GHSR-1a distributed throughout the brain, being mainly enriched in pituitary, cortex and hippocampus (Hp) modulating a variety of brain functions. Behavioral, electrophysiological and biochemical evidence indicated that Gr modulates the excitability and the synaptic plasticity in Hp. The present experiments were designed in order to extend the knowledge about the Gr effect upon structural synaptic plasticity since morphological and quantitative changes in spine density after Gr administration were analyzed "in vitro" and "in vivo". The results show that Gr administered to hippocampal cultures or stereotactically injected in vivo to Thy-1 mice increases the density of dendritic spines (DS) being the mushroom type highly increased in secondary and tertiary extensions. Spines classified as thin type were increased particularly in primary extensions. Furthermore, we show that Gr enhances selectively the expression of BDNF-mRNA species.

Paternal Deprivation and Female Biparental Family Rearing Induce Dendritic and Synaptic Changes in Octodon degus: I. Medial Prefrontal Cortex.

In most mammalian species parent-offspring interactions during early life periods primarily comprise social contacts with the mother, whereas the role of males in parental care is one of the most overlooked and understudied topics. The present study addressed the hypothesis that the complete deprivation of paternal care delays or permanently retards synaptic connectivity in the brain, particularly in the medial prefrontal cortex (mPFC) of the offspring in a sex-specific manner. Another aim of this study was to address the question whether and in which way replacing the father with a female caregiver (in our experiments the "aunt") can "buffer" the detrimental effects of paternal deprivation on neuronal development. The comparison of: (a) single mother rearing; (b) biparental rearing by father and mother; and (c) biparental rearing by two female caregivers revealed that: (i) paternal care represents a critical environmental factor for synaptic and dendritic development of pyramidal neurons in the vmPFC of their offspring; (ii) a second female caregiver ("aunt") does not "buffer" the neuronal consequences of paternal deprivation; and that (iii) neuronal development in the vmPFC is differentially affected in male and female offspring in response to different family constellations.

Neuronal plasticity in the forebrain of the male red-sided garter snake: Effect of season, low temperature dormancy, and hormonal status on dendritic spine density.

Numerous studies have reported seasonal variations in regional morphology in the brains of seasonally breeding vertebrates. These alterations of neuronal morphology and dendritic spine density appear to be an active process within specific brain nuclei that regulate seasonal behaviors. In many cases, this neural plasticity has been found to be in response to changes in circulating sex steroid hormone levels and occur within pathways essential for the control of reproductive behaviors. Male red-sided garter snakes (Thamnophis sirtalis parietalis) (RSGS) exhibit a dissociated reproductive pattern where mating is initiated at a time when the gonads and steroidogenesis are inactive. And, although circulating levels of sex steroid hormones are elevated at the initiation of courtship and mating, the only known cue found to initiate courtship behavior and mating, is an extended period of low temperature dormancy (LTD) followed by exposure to warm temperatures. This study was designed to examine the role of seasons, sex steroid hormones, and LTD on neuronal and dendritic spine density within the anterior hypothalamus-preoptic area (AHPOA), a region shown to be critical for the regulation of reproductive behaviors. In the male RSGS, the density of dendritic spines on neurons in the AHPOA was significantly greater in spring, actively courting animals, than summer or fall, non-courting animals. Animals maintained under conditions of LTD exhibited significantly increasing spine density as time maintained in LTD increased. Animals receiving either testosterone or estradiol had a significantly greater density of dendritic spines than control animals. This study offers evidence suggesting that the "set up" of the pathways controlling courtship behavior and mating in the male RSGS, is not due solely to an extended period of LTD, but that an extended period of LTD in conjunction with circulating sex steroid hormones are critical for the initiation of reproductive behavior.

Functional clustering of dendritic activity during decision-making.

The active properties of dendrites can support local nonlinear operations, but previous imaging and electrophysiological measurements have produced conflicting views regarding the prevalence and selectivity of local nonlinearities in vivo. We imaged calcium signals in pyramidal cell dendrites in the motor cortex of mice performing a tactile decision task. A custom microscope allowed us to image the soma and up to 300 µm of contiguous dendrite at 15 Hz, while resolving individual spines. New analysis methods were used to estimate the frequency and spatial scales of activity in dendritic branches and spines. The majority of dendritic calcium transients were coincident with global events. However, task-associated calcium signals in dendrites and spines were compartmentalized by dendritic branching and clustered within branches over approximately 10 µm. Diverse behavior-related signals were intermingled and distributed throughout the dendritic arbor, potentially supporting a large learning capacity in individual neurons.

A 2x folic acid treatment affects epigenetics and dendritic spine densities in SHSY5Y cells.

Many diseases are now associated with aberrant epigenetics and gene expression changes. Epigenetics can be modified by factors like diet. One dietary factor, folic acid, is consumed in various forms including supplements, energy drinks, and fortified grains. It was hypothesized high levels of folic acid would affect gene expression and enzyme activity of chromatin modifying enzymes as well as dendritic spine densities in a commonly utilized neuron model, the SHSY5Y cell. Decreased MBD2 and MECP2 were discovered upon treatment of SHSY5Y cells with a 2x folic acid dose. Corresponding decreases in dendritic spines were apparent in the 2x folic acid treated cells as well. Activity of DNMTs and H3K4 HMTs was altered. Further, H3K4me1, H3K4me3, H3K9Ac, and global DNA methylation were decreased in the 2x folic acid treated cells. Further studies are warranted to determine if the effects of excess folic acid are detrimental to organismal physiology.

Regulation of Neprilysin Activity and Cognitive Functions in Rats After Prenatal Hypoxia.

The amyloid-degrading enzyme neprilysin (NEP) is one of the therapeutic targets in prevention and treatment of Alzheimer's disease (AD). As we have shown previously NEP expression in rat parietal cortex (Cx) and hippocampus (Hip) decreases with age and is also significantly reduced after prenatal hypoxia. Following the paradigms for enhancement of NEP expression and activity developed in cell culture, we analysed the efficacy of various compounds able to upregulate NEP using our model of prenatal hypoxia in rats. In addition to the previous data demonstrating that valproic acid can upregulate NEP expression both in neuroblastoma cells and in rat Cx and Hip we have further confirmed that caspase inhibitors can also restore NEP expression in rat Cx reduced after prenatal hypoxia. Here we also report that administration of a green tea catechin epigallocatechin-3-gallate (EGCG) to adult rats subjected to prenatal hypoxia increased NEP activity in blood plasma, Cx and Hip as well as improved memory performance in the 8-arm maze and novel object recognition tests. Moreover, EGCG administration led to an increased number of dendritic spines in the hippocampal CA1 area which correlated with memory enhancement. The data obtained allowed us to conclude that the decrease in the activity of the amyloid-degrading enzyme NEP, as well as a reduction in the number of labile interneuronal contacts in the hippocampus, contribute to early cognitive deficits caused by prenatal hypoxia and that there are therapeutic avenues to restore these deficits via NEP activation which could also be used for designing preventive strategies in AD.

Timing is everything: differential effects of chronic stress on fear extinction.

RATIONALE: Stress disorders cause abnormal regulation of fear-related behaviors. In most rodent models of these effects, stress was administered before fear conditioning, thereby assessing its impact on both the formation and extinction of fear memories, not the latter alone. Here, we dissociated the two processes by also administering stress after fear conditioning, and then compared how pre-conditioning versus post-conditioning exposure to chronic stress affects subsequent acquisition and recall of fear extinction. METHODS: Male Wistar rats were subjected to chronic immobilization stress (2 h/day, 10 days); the morphological effects of which were analyzed using modified Golgi-Cox staining across brain areas mediating the formation and extinction of fear memories. Separate groups of rats underwent fear conditioning followed by acquisition and recall of extinction, wherein stress was administered either before or after fear conditioning. RESULTS: When fear memories were formed after chronic stress, both acquisition and retrieval of extinction was impaired. Strikingly, these deficits were absent when fear memories were formed before the same stress. Chronic stress also reduced dendritic spine density in the infralimbic prefrontal cortex, but enhanced it in the basolateral amygdala. CONCLUSION: Chronic stress, administered either before or after fear learning, had distinct effects on the acquisition and recall of fear extinction memories. Stress also strengthened the structural basis of synaptic connectivity in the amygdala, but weakened it in the prefrontal cortex. Thus, despite eliciting a specific pattern of brain region-specific morphological changes, the timing of the same stress gave rise to strikingly different behavioral effects on the extinction of fear.

[Effect of Electroacupuncture on Learning-memory Ability in Rats with Hypoxic-ischemic Encephalopathy].

OBJECTIVE: To observe the effect of electroacupuncture (EA) on changes of learning-memory ability, psychomotor coordination and anxiety-like behavior of cerebral hypoxic-ischemia (CHI) young rats, so as to explore its protective effect on neurons under hypoxic-ischemic conditions. METHODS: SD rats (aged 7 days) were randomly divided into sham operation (sham, n=12), model (n=11), and EA groups (n=12). In addition, 6 young rats in each group were used for observing the number of dendritic spines after Golgi staining. The CHI model was established by ligation of the left common carotid artery combined with hypoxia in a closed transparent vessel. EA was applied to "Baihui" (GV 20)and "Dazhui" (GV 14) for 20 min, once every other day, for 28 days. The rats' behavior changes were assessed by using rotarod performance (for psychomotor coordination), elevated plus maze (anxiety-like behavior) tests and Morris water maze (learning-memory ability) tests, separately. RESULTS: After modeling, the average escape latency and average escape distance of location navigation test within 70 seconds were significantly increased (P<0.05), and the average times and average duration of safe-platform quadrant crossing of spacial probing test were markedly reduced relevant to the sham group (P<0.05). After EA treatment, CHI-induced increases of escape latency and escape distance, and the decreased times and duration of platform quadrant crossing were significantly reversed (P<0.05). No significant differences were found among the three groups in the falling latency of rotarod performance test, and in the time of opening and closing arms of elevated plus maze tests (P>0.05). The density of dendritic spines was significantly lo-wer in the model group than in the sham group (P <0.05), and notably higher in the EA group than in the model group (P<0.05). CONCLUSION: EA can improve the learning-memory ability of CHI young rats, which may be related to its effect in protecting the dendritic spines of CA 1 region of hippocampus from injury.

Effect of Electroacupuncture on Learning-memory Ability in Rats with Hypoxic-ischemic Encephalopathy / 针刺研究

OBJECTIVE: To observe the effect of electroacupuncture (EA) on changes of learning-memory ability, psychomotor coordination and anxiety-like behavior of cerebral hypoxic-ischemia (CHI) young rats, so as to explore its protective effect on neurons under hypoxic-ischemic conditions. METHODS: SD rats (aged 7 days) were randomly divided into sham operation (sham, n=12), model (n=11), and EA groups (n=12). In addition, 6 young rats in each group were used for observing the number of dendritic spines after Golgi staining. The CHI model was established by ligation of the left common carotid artery combined with hypoxia in a closed transparent vessel. EA was applied to "Baihui" (GV 20)and "Dazhui" (GV 14) for 20 min, once every other day, for 28 days. The rats' behavior changes were assessed by using rotarod performance (for psychomotor coordination), elevated plus maze (anxiety-like behavior) tests and Morris water maze (learning-memory ability) tests, separately. RESULTS: After modeling, the average escape latency and average escape distance of location navigation test within 70 seconds were significantly increased (P0.05). The density of dendritic spines was significantly lo-wer in the model group than in the sham group (P <0.05), and notably higher in the EA group than in the model group (P<0.05). CONCLUSION: EA can improve the learning-memory ability of CHI young rats, which may be related to its effect in protecting the dendritic spines of CA 1 region of hippocampus from injury.

Tripeptides Restore the Number of Neuronal Spines under Conditions of In Vitro Modeled Alzheimer's Disease.

In primary culture of mouse hippocampal neurons, peptide EDR (200 ng/ml) under conditions of amyloid synaptotoxicity (a model of Alzheimer's disease) increased the number of mushroom spines by 71% and returned this parameter to the normal level. Under the same conditions, tripeptide KED (200 ng/ml) increased the number of mushroom spines in hippocampal neurons by 20%. Tripeptide EDR can be recommended for further experimental study as a candidate neuroprotective agent for prevention and treatment of Alzheimer's disease.