Hippocampal Pathway Research Articles

The effects of vagus nerve stimulation on hippocampal neuro-inflammatory and α7nAChR expression in rats with intractable epilepsy

Objective: To investigate the effects of vagus nerve stimulation(VNS) on hippocampal neuro-inflammatory and α7 nicotinic acetylcholine receptor (α7nAChR) expression in rats with intractable epilepsy (IE). Methods: Eighty adult male SD rats (SPF) were randomly divided into control group, model group, VNS group and MLA+VNS group. There were respectively 20 rats in the control group and MLA+VNS group, and because of model failure and animal death, 15 rats and 14 rats in the model group and VNS group were left respectively . Except the control group, the IE model was established in other groups. Only the vagus nerve was isolated in the control group without electrical stimulation; the model group did not take any intervention measures; the VNS group was treated for 4 weeks with VNS after the model was successful; the MLA(3.4 μg/μl, 5 μl) was given to the lateral ventricle in the MLA+VNS group, and then VNS for 4 weeks. Seizure frequency and duration in each group were observed and recorded. And then the rats were decapitated, the hippocampus were quickly separated and 10% tissue homogenate was prepared. The homogenate was centrifuged and the supernatant was extracted. The activities of AChE and ChAT in the supernatant were measured by spectrophotometry, and the levels of TNF-ɑ, IL-6 and IL-1β were detected by ELISA. The expression of α7nAChR in rat hippocampals was detected by Western blot. The expression of α7nAChR on microglias in rat hippocampals was assesed by double-labeled immunofluorescence. Results: ①After VNS for 4 weeks, the frequency and duration of seizures in rats were decreased significantly, which were lower than those of the model group (P<0.01); After treated with MLA +VNS, the frequency and duration of seizures in rats were also reduced significantly, which were lower than those of the model group, but higher than those of the VNS group (P<0.01).②Compared with the control group, the expression of ChAT in the hippocampus of rats in the model group was decreased significantly and the expression of AChE was increased significantly (P<0.01); Compared with the model group, the expressions of ChAT in the hippocampus of rats in the VNS group and MLA+VNS group were increased significantly and the expressions of AChE were decreased significantly (P<0.01); Compared with the VNS group, in the hippocampus of rats in the MLA+VNS group, the expressions of ChAT and AChE had no significant changes (P>0.05). ③Compared with the control group, the expressions of TNF-ɑ, IL-6 and IL-1β in the hippocampus of rats in the model group were increased significantly (P<0.01). Compared with the model group, the expressions of TNF-ɑ, IL-6 and IL-1β in the hippocampus of rats in the VNS group were decreased significantly (P<0.01). Compared with the VNS group, the expressions of TNF-ɑ, IL-6 and IL-1β in the hippocampus of rats in the MLA+VNS group were increased significantly(P<0.01). ④Compared with the control group, the expression of α7nAChR in hippocampus and microglia of rats in the model group was decreased significantly(P<0.01); Compared with the model group, the expression of α7nAChR in hippocampus and microglia of rats in the VNS group was up-regulated significantly (P<0.01); Compared with the VNS group, coexpression of α7nAChR on microglia wasreduced significantly in the MLA+VNS group (P<0.01). Conclusion: VNS has obvious therapeutic effect on IE rats, and its mechanism may be related to activating hippocampal microglia cholinergic anti-inflammatory pathway directly and inhibiting hippocampal neuro-inflammatory response.

Recovery from the damage of cranial radiation modulated by memantine, an NMDA receptor antagonist, combined with hyperbaric oxygen therapy.

Radiotherapy is an important treatment option for central nervous system malignancies. However, cranial radiation induces hippocampal dysfunction and white matter injury; this leads to cognitive dysfunction, and results in a reduced quality of life in patients. Excitatory glutamate signaling through N-methyl-d-aspartate receptors (NMDARs) plays a central role both in hippocampal neurogenesis and in the myelination of oligodendrocytes in the cerebrum. We provide a method for quantifying neurogenesis in human subjects in live brain during cancer therapy. Neuroimaging using originally created behavioral tasks was employed to examine human hippocampal memory pathway in patients with brain disorders. Treatment with memantine, a non-competitive NMDAR antagonist, reversed impairment in hippocampal pattern separation networks as detected by functional magnetic resonance imaging. Hyperbaric preconditioning of the patients just before radiotherapy with memantine mostly reversed white matter injury as detected by whole brain analysis with Tract-Based Spatial Statics. Neuromodulation combined with the administration of hyperbaric oxygen therapy and memantine during radiotherapy facilitated the restoration of hippocampal function and white matter integrity, and improved higher cognitive function in patients receiving cranial radiation. The method described herein, for diagnosis of hippocampal dysfunction, and therapeutic intervention can be utilized to restore some of the cognitive decline experienced by patients who have received cranial radiation. The underlying mechanism of restoration is the production of new neurons, which enhances functionality in pattern separation networks in the hippocampi, resulting in an increase in cognitive score, and restoration of microstructural integrity of white matter tracts revealed by Tract-Based Spatial Statics Analysis.

Altered PVN-to-CA2 hippocampal oxytocin pathway and reduced number of oxytocin-receptor expressing astrocytes in heart failure rats.

Oxytocinergic actions within the hippocampal CA2 are important for neuromodulation, memory processing and social recognition. However, the source of the OTergic innervation, the cellular targets expressing the OT receptors (OTRs) and whether the PVN-to-CA2 OTergic system is altered during heart failure (HF), a condition recently associated with cognitive and mood decline, remains unknown. Using immunohistochemistry along with retrograde monosynaptic tracing, RNAscope and a novel OTR-Cre rat line, we show that the PVN (but not the supraoptic nucleus) is an important source of OTergic innervation to the CA2. These OTergic fibers were found in many instances in close apposition to OTR expressing cells within the CA2. Interestingly, while only a small proportion of neurons were found to express OTRs (~15%), this expression was much more abundant in CA2 astrocytes (~40%), an even higher proportion that was recently reported for astrocytes in the central amygdala. Using an established ischemic rat heart failure (HF) model, we found that HF resulted in robust changes in the PVN-to-CA2 OTergic system, both at the source and target levels. Within the PVN, we found an increased OT immunoreactivity, along with a diminished OTR expression in PVN neurons. Within the CA2 of HF rats, we observed a blunted OTergic innervation, along with a diminished OTR expression, which appeared to be restricted to CA2 astrocytes. Taken together, our studies highlight astrocytes as key cellular targets mediating OTergic PVN inputs to the CA2 hippocampal region. Moreover, they provide the first evidence for an altered PVN-to-CA2 OTergic system in HF rats, which could potentially contribute to previously reported cognitive and mood impairments in this animal model.

HIV-1 Tat reduces apical dendritic spine density throughout the trisynaptic pathway in the hippocampus of male transgenic mice

Nearly one-third of persons infected with HIV-1 (PWH) develop HIV-associated neurocognitive disorders (HAND), which can be exacerbated by exposure to opioids. The impact of opioids on HIV-induced alterations in neuronal plasticity is less well understood. Both morphine exposure and HIV have been shown to disrupt synaptic growth and stability in the hippocampus suggesting a potential site of convergence for their deleterious effects. In the present study, we examined the density of dendritic spines in CA1 and CA3 pyramidal neurons, and granule neurons within the dentate gyrus representing the hippocampal trisynaptic pathway after short-term exposure to the HIV transactivator of transcription (Tat) protein and morphine. We exposed inducible male, HIV-1 Tat transgenic mice to escalating doses of morphine (10–40 mg/kg, b.i.d.) and examined synaptodendritic structure in Golgi-impregnated hippocampal neurons. HIV-1 Tat, but not morphine, systematically reduced the density of apical, but not basilar, dendrites of CA1 and CA3 pyramidal neurons, and granule neuronal apical dendrites, suggesting the coordinated loss of specific synaptic interconnections throughout the hippocampal trisynaptic pathway.

Terpenoid Backbone Biosynthesis among Pig Hippocampal Pathways Impacted by Stressors.

Neurogenomic changes induced by maternal immune activation (MIA) during gestation and the social stress of weaning can alter brain plasticity in the hippocampus of offspring. The present study furthers the understanding of how these stressors impact hippocampus gene networks. The hippocampus transcriptome was profiled in pigs that were either exposed to MIA or not and were weaned or nursed. Overall, 1576 genes were differentially expressed (FDR-adjusted p-value < 0.05 and |log2 (fold change between pig groups)| > 1.2) in response to the main and interacting effects of MIA, weaning, and sex. Functional analysis identified 17 enriched immunological and neurological pathways in the Kyoto Encyclopedia of Genes and Genomes database. The enrichment of the terpenoid backbone biosynthesis pathway was characterized by genes under-expressed in MIA relative to non-MIA exposed, males relative to females, and weaned relative to nursed pigs. On the other hand, the enrichment of drug addiction pathways was characterized by gene over-expression in MIA relative to non-exposed pigs. Our results indicate that weaning and sex can modify the effects of MIA on the offspring hippocampus. This knowledge can aid in precise identification of molecular targets to reduce the prolonged effects of pre- and postnatal stressors.

Chronic exposure of bisphenol-A impairs cognitive function and disrupts hippocampal insulin signaling pathway in male mice

Bisphenol-A (BPA), a well-known estrogenic endocrine disruptor, is generally applied to turn out plastic consumer products. Available data have manifested that exposure to BPA can trigger insulin resistance. Hence, the purpose of the actual study was to consider the impacts of BPA exposure on cognitive function and insulin signaling pathway in the hippocampus of male offspring mice. For this purpose, the pregnant female mice were treated either vehicle (0.1% ethanol) or BPA (0.01, 0.1, and 1 µg/mL) via drinking water from day 1 of gestation until delactation (D1-PND21, newborn exposure). Afterward, the three-week-old male offspring mice took orally with the same doses of BPA for nine weeks (PND84). The behavioral tests, blood sugar level, histological observation, transcriptome sequencing, glucose transporter 4 (GLUT4), and hippocampal insulin signaling pathway were checked for the male offspring mice at 13 weeks of age (PND91). Our data indicated that BPA exposure impaired cognitive function, disrupted the hippocampal regular cell arrangement, increased blood glucose levels, disturbed the insulin signaling pathway including phosphorylated insulin receptor substrate1 (p-IRS1), protein kinase B (p-AKT), and glycogen synthase kinase 3β (p-GSK3β). At the same time, the mRNA and protein expressions of GLUT4 were markedly down-regulated in the BPA-exposed groups. To sum up, it has been suggested from these results that BPA has detrimental effects on the insulin signaling pathway, which might subsequently be conducive to the impairment of cognitive function in the adult male offspring mice. Therefore, BPA exposure might in part be an element of risk for the long-term neurodegeneration in male offspring mice.

Simvastatin rescues memory and granule cell maturation through the Wnt/\u03b2-catenin signaling pathway in a mouse model of Alzheimer\u2019s disease

We previously showed that simvastatin (SV) restored memory in a mouse model of Alzheimer disease (AD) concomitantly with normalization in protein levels of memory-related immediate early genes in hippocampal CA1 neurons. Here, we investigated age-related changes in the hippocampal memory pathway, and whether the beneficial effects of SV could be related to enhanced neurogenesis and signaling in the Wnt/β-catenin pathway. APP mice and wild-type (WT) littermate controls showed comparable number of proliferating (Ki67-positive nuclei) and immature (doublecortin (DCX)-positive) granule cells in the dentate gyrus until 3 months of age. At 4 months, Ki67 or DCX positive cells decreased sharply and remained less numerous until the endpoint (6 months) in both SV-treated and untreated APP mice. In 6 month-old APP mice, dendritic extensions of DCX immature neurons in the molecular layer were shorter, a deficit fully normalized by SV. Similarly, whereas mature granule cells (calbindin-immunopositive) were decreased in APP mice and not restored by SV, their dendritic arborizations were normalized to control levels by SV treatment. SV increased Prox1 protein levels (↑67.7%, p < 0.01), a Wnt/β-catenin signaling target, while significantly decreasing (↓61.2%, p < 0.05) the upregulated levels of the β-catenin-dependent Wnt pathway inhibitor DKK1 seen in APP mice. In APP mice, SV benefits were recapitulated by treatment with the Wnt/β-catenin specific agonist WAY-262611, whereas they were fully abolished in mice that received the Wnt/β-catenin pathway inhibitor XAV939 during the last month of SV treatment. Our results indicate that activation of the Wnt-β-catenin pathway through downregulation of DKK1 underlies SV neuronal and cognitive benefits.

Learning Ability and Hippocampal Transcriptome Responses to Early and Later Life Environmental Complexities in Dual-Purpose Chicks.

Simple SummaryThe hippocampus region of birds is a pivotal area for learning and memory. Early-life conditions can have a long-lasting impact on animals. However, the influence of early-life and later-life environments on animals’ health and welfare has not been well-studied. This study addresses the impact of early-life enrichment and the later environment on the learning ability and hippocampal responses in chicks. We found that the early-life environmental complexity did not prepare better for learning ability in response to life challenges in the future. This study indicates that perches and litter materials, which enriched early-life conditions, were conducive to improved stress responses later in life in terms of neural- and immune-related gene expression and functional pathways. This can be attributed to the “silver spoon” effect. However, the enrichment through litter materials alone in early life does not improve the hippocampal plasticity in later stressed environments. In addition, early-life barren conditions that match later-life conditions have beneficial impacts on neural development, supporting the match and mismatch theory. This study helps us to understand the relationship between early- and later-life environments from the perspective of animal neural- and immune-related development. It also has the potential to guide the treatment of mental problems and personal health in humans based on the interactions between the early-life and later-life environments. In this study, we hypothesized that complex early-life environments enhance the learning ability and the hippocampal plasticity when the individual is faced with future life challenges. Chicks were divided into a barren environment group (BG), a litter materials group (LG), and a perches and litter materials group (PLG) until 31 days of age, and then their learning abilities were tested following further rearing in barren environments for 22 days. In response to the future life challenge, the learning ability showed no differences among the three groups. In the hippocampal KEGG pathways, the LG chicks showed the downregulation of neural-related genes neuronal growth regulator 1 (NEGR1) and neurexins (NRXN1) in the cell adhesion molecules pathway compared to the BG (p < 0.05). Immune-related genes TLR2 in Malaria and Legionellosis and IL-18 and IL18R1 in the TNF signaling pathway were upregulated in the LG compared to in the BG (p < 0.05). Compared to the BG, the PLG displayed upregulated TLR2A in Malaria (p < 0.05). The PLG showed upregulated neural-related gene, i.e., neuronal acetylcholine receptor subunit alpha-7-like (CHRNA8) in the nicotine addiction pathway and secretagogin (SCGN) gene expression, as compared to the LG (p < 0.05). In conclusion, early-life environmental complexities had limited effects on the learning ability in response to a future life challenge. Early-life perches and litter materials can improve neural- and immune-related gene expression and functional pathways in the hippocampus of chicks.

The Impact of the hAPP695SW Transgene and Associated Amyloid-β Accumulation on Murine Hippocampal Biochemical Pathways.

Alzheimer's disease (AD) is a neurodegenerative disease characterized by the accumulation of amyloid-β (Aβ) peptide in the brain. To gain a better insight into alterations in major biochemical pathways underlying AD. We compared metabolomic profiles of hippocampal tissue of 20-month-old female Tg2576 mice expressing the familial AD-associated hAPP695SW transgene with their 20-month-old wild type female littermates. The hAPP695SW transgene causes overproduction and accumulation of Aβ in the brain. Out of 180 annotated metabolites, 54 metabolites differed (30 higher and 24 lower in Tg2576 versus wild-type hippocampal tissue) and were linked to the amino acid, nucleic acid, glycerophospholipid, ceramide, and fatty acid metabolism. Our results point to 1) heightened metabolic activity as indicated by higher levels of urea, enhanced fatty acid β-oxidation, and lower fatty acid levels; 2) enhanced redox regulation; and 3) an imbalance of neuro-excitatory and neuro-inhibitory metabolites in hippocampal tissue of aged hAPP695SW transgenic mice. Taken together, our results suggest that dysregulation of multiple metabolic pathways associated with a concomitant shift to an excitatory-inhibitory imbalance are contributing mechanisms of AD-related pathology in the Tg2576 mouse.

Magnetic resonance imaging features of hippocampus and mechanism of neurocognitive dysfunction for antiepileptic drugs in treatment of depression rats

ABSTRACT To explore the effects of antiepileptic drug sodium valproate on magnetic resonance imaging (MRI) images, neurological cognition, and JAK1/STAT3 pathway in hippocampus of rats with depression, 30 Sprague Dawley (SD) rats were included. The depression model (DM) was prepared through the chronic stress restraint test. Some model rats were injected with 10 mg/kg sodium valproate into abdominal cavity before modeling (RT group)), and healthy rats were selected as controls (healthy control (HC) group). Depth of split brain was greatly increased in DM group, and nitrogen-acetyl aspartic acid (NAA)/creatine (Cr), glutamic acid (Glu)/Cr, and choline (Cho)/Cr ratios were greatly reduced (P < 0.05). Behavioral test results showed that sugar water preference rate, escape latency, and divergence index in DM group were greatly reduced (P < 0.05), and cumulative immobility time, target quadrant stay time, and number of crossings in forced swimming and tail suspension were prolonged dramatically (P < 0.05), with no difference between the two groups (P > 0.05). Expression levels of interleukin 1β (IL-1β) and interleukin 6 (IL-6) in hippocampus of DM group were obviously increased (P < 0.05), and expression levels of JAK1 and STAT3 were decreased visibly (P < 0.05), with no difference between the two (P > 0.05). In summary, anti-epileptic drug sodium valproate effectively improves hippocampal volume characteristics and memory and neurocognitive dysfunction of depression models.

Effects of electroacupuncture with different frequencies on hippocampal neuronal apoptosis and JNK signaling pathway in rats with vascular dementia

Effects of electroacupuncture with different frequencies on hippocampal neuronal apoptosis and JNK signaling pathway in rats with vascular dementia

Role of extracellular signal-regulated kinase in rubrofusarin-enhanced cognitive functions and neurite outgrowth

Memory-enhancing agents have long been required for various reasons such as for obtaining a good score in a test in the young and for retaining memory in the aged. Although many studies have found that several natural products may be good candidates for memory enhancement, there is still a need for better agents. The present study investigated whether rubrofusarin, an active ingredient in Cassiae semen, enhances learning and memory in normal mice. Passive avoidance and Morris water maze tests were performed to determine the memory-enhancing ability of rubrofusarin. To investigate synaptic function, hippocampal long-term potentiation (LTP) was measured. Western blotting was performed to determine protein levels. To investigate neurite outgrowth, DCX immunohistochemistry and cell culture were utilised. Rubrofusarin (1, 3, 10, 30 mg/kg) enhanced memory in passive avoidance and Morris water maze tests. Moreover, rubrofusarin ameliorated scopolamine-induced memory impairment. In the rubrofusarin-treated group, high-frequency stimulation induced higher LTP in the hippocampal Schaffer-collateral pathway compared to the control group. The rubrofusarin-treated group showed a higher number of DCX-positive immature neurons with an increase in the length of dendrites compared to the control group in the hippocampal dentate gyrus region. In vitro experiments showed that rubrofusarin facilitated neurite outgrowth in neuro2a cells through extracellular signal-regulated kinase (ERK). Finally, we found that extracellular signal-regulated kinase (ERK) is required for rubrofusarin-induced enhancement of neurite outgrowth, learning and memory. These results demonstrate that rubrofusarin enhances learning and memory and neurite outgrowth, and these might need activation of ERK pathway.

Dynamic balance deficit and the neural network in Alzheimer's disease and mild cognitive impairment

BackgroundPatients with Alzheimer’s disease (AD) and mild cognitive impairment (MCI) exhibit balance deficits. Although only a few studies have evaluated the relationship between the brain images and balance indices. In this study, we measured balance indices, including the index of postural stability (IPS) and assessed the relationship between the brain images and their clinical motor and cognitive functional features. MethodsThe study included patients with MCI (N = 14) and patients with AD (N = 19). The primary outcome was IPS under a visual block condition and/or a proprioception block condition. In addition, 9 MCI and 8 AD patients underwent a 1.5-Tesla (1.5-T) Magnetic Resonance Imaging (MRI) scan, and the relationships between the MRI parameters and the balance indices were evaluated. ResultsThe IPS score was significantly lower in the AD group than the MCI group, but only under the closed eyes/hard surface condition. In terms of MRI, there was a significant positive correlation between the IPS and the regional betweenness centrality in the left hippocampal region. ConclusionsThe finding of a significantly lower IPS score under the closed eyes/hard surface condition in AD than in MCI cases suggests that the vestibular and/or proprioceptive systems were more severely impaired in AD than MCI cases. The results suggest that a dynamic balance disturbance due to deficits of the vestibular hippocampal pathway may be a useful marker for the diagnosis of MCI and detection of disease progression from MCI to AD.

The structural aspects of neural dynamics and information flow.

Neurons have specialized structures that facilitate information transfer using electrical and chemical signals. Within the perspective of neural computation, the neuronal structure is an important prerequisite for the versatile computational capabilities of neurons resulting from the integration of diverse synaptic input patterns, complex interactions among the passive and active dendritic local currents, and the interplay between dendrite and soma to generate action potential output. For this, characterization of the relationship between the structure and neuronal spike dynamics could provide essential information about the cellular-level mechanism supporting neural computations. This work describes simulations and an information-theoretic analysis to investigate how specific neuronal structure affects neural dynamics and information processing. Correlation analysis on the Allen Cell Types Database reveals biologically relevant structural features that determine neural dynamics-eight highly correlated structural features are selected as the primary set for characterizing neuronal structures. These features are used to characterize biophysically realistic multi-compartment mathematical models for primary neurons in the direct and indirect hippocampal pathways consisting of the pyramidal cells of Cornu Ammonis 1 (CA1) and CA3 and the granule cell in the dentate gyrus (DG). Simulations reveal that the dynamics of these neurons vary depending on their specialized structures and are highly sensitive to structural modifications. Information-theoretic analysis confirms that structural factors are critical for versatile neural information processing at a single-cell and a neural circuit level; not only basic AND/OR but also linearly non-separable XOR functions can be explained within the information-theoretic framework. Providing quantitative information on the relationship between the structure and the dynamics/information flow of neurons, this work would help us understand the design and coding principles of biological neurons and may be beneficial for designing biologically plausible neuron models for artificial intelligence (AI) systems.

Electroacupuncture Prevents the Depression-Like Behavior by Inhibiting the NF-κB/NLRP3 Inflammatory Pathway in Hippocampus of Mice Subjected to Chronic Mild Stress

Background: The precise physiological mechanisms of acupuncture in the treatment of depression are still unknown. This study aimed to observe the effects of electroacupuncture (EA) on depression-like behavior of mouse in chronic mild stress (CMS) model and explore the underlying mechanism. Methods: The depression model was established by using CMS method for 6 weeks. After the third week of the CMS paradigm, EA treatment was performed daily for 15 min over a period of 3 weeks. The antidepressant-like effects of EA were evaluated using the sucrose preference test and the forced swimming test (FST). The protein levels of the nuclear factor-kappa B (NF-κB), p-NF-κB, inhibitor of NF-κB, p-IκBα, NOD-like receptor protein 3, interleukin (IL)-6, IL-1β, IL-18, and tumor necrosis factor-α (TNF-α) in hippocampus of mice were detected. Results: Sucrose preference was decreased after 6 weeks of CMS and the effects of CMS was reversed by EA. CMS increased immobility time and decreased latency to the first immobility in the FST test, but these effects were reversed by EA. CMS-induced nuclear entry of NF-κB (nuclear/cytoplasmic ratio of NF-κB) with an increase in protein levels of p-NF-κB and p-IκBα in the hippocampus. The CMS also increased NLRP3 levels in the hippocampus. However, these effects were reversed by EA. In addition, the levels of IL-6, IL-1β, IL-18, and TNF-α in the hippocampus were increased by CMS, and these effects of stress were reversed by EA. Conclusion: EA prevented CMS-induced depressive-like behaviors by inhibiting NF-κB/NLRP3 inflammatory pathway.

Acupuncture Relieves Stress-Induced Depressive Behavior by Reducing Oxidative Stress and Neuroapoptosis in Rats.

Oxidative stress is closely related to the occurrence of depression. Acupuncture has been proved to be an effective method for treating depression. In order to explore the mechanism of the antidepressant effect of acupuncture, this study performed acupuncture prevention on chronic unpredictable mild stress (CUMS) depression model rats, and observed the effect of acupuncture on hippocampal oxidative stress and Nrf2 signaling pathway. Male SD rats were randomly divided into control group, CUMS group, acupuncture group, and fluoxetine group (n = 10/group). Fluoxetine, a common antidepressant, was used as a positive control drug in this study. In the fluoxetine group, rats were given fluoxetine (2.1 mg/kg) intragastrically once a day for 28 days. The acupoints of Shangxing (GV23) and Fengfu (GV16) were applied in acupuncture group, once every other day for 14 times in total. Behavioral tests and biological detections were used to evaluate the effects of the interventions and the changes of factors related to oxidative stress, Nrf2 pathway, and neuronal apoptosis. The results showed that both acupuncture and fluoxetine could increase sugar preference rate in SPT and decrease immobility time in FST in depression model rats. It also significantly decreased oxidative stress products such as ROS and H2O2, and elevated the protein and mRNA expressions of Nrf2 and HO-1. From Nissl’s staining, there were more abundant nerve cells in two intervention groups compared with CUMS group. Plus, acupuncture down-regulated the expression levels of Bax and caspase-3 and up-regulated the expression of Bcl-2. Our findings indicate that acupuncture improved depression-like behaviors of CUMS rats. And CUMS-induced depression-like behaviors in rats were related to oxidative stress and neuronal apoptosis in hippocampus. Acupuncture showed antidepressant effects in reducing oxidative stress products via regulating the Nrf2/HO-1 signaling pathway so that prevented neuronal apoptosis.

Hyperactivation &amp;nbsp;of TRPV4 Causes the Hippocampal Pyroptosis Pathway and Results in Cognitive Impairment in LPS - Treated Mice

Hyperactivation &amp;nbsp;of TRPV4 Causes the Hippocampal Pyroptosis Pathway and Results in Cognitive Impairment in LPS - Treated Mice

Oxytocin treatment inhibits dexamethasone-induced depression by activating the hippocampal CREB-BDNF signaling pathway in female mice

Background

Noncanonical projections to the hippocampal CA3 regulate spatial learning and memory by modulating the feedforward hippocampal trisynaptic pathway.

The hippocampal formation (HF) is well documented as having a feedforward, unidirectional circuit organization termed the trisynaptic pathway. This circuit organization exists along the septotemporal axis of the HF, but the circuit connectivity across septal to temporal regions is less well described. The emergence of viral genetic mapping techniques enhances our ability to determine the detailed complexity of HF circuitry. In earlier work, we mapped a subiculum (SUB) back projection to CA1 prompted by the discovery of theta wave back propagation from the SUB to CA1 and CA3. We reason that this circuitry may represent multiple extended noncanonical pathways involving the subicular complex and hippocampal subregions CA1 and CA3. In the present study, multiple retrograde viral tracing approaches produced robust mapping results, which supports this prediction. We find significant noncanonical synaptic inputs to dorsal hippocampal CA3 from ventral CA1 (vCA1), perirhinal cortex (Prh), and the subicular complex. Thus, CA1 inputs to CA3 run opposite the trisynaptic pathway and in a temporal to septal direction. Our retrograde viral tracing results are confirmed by anterograde-directed viral mapping of projections from input mapped regions to hippocampal dorsal CA3 (dCA3). We find that genetic inactivation of the projection of vCA1 to dCA3 impairs object-related spatial learning and memory but does not modulate anxiety-related behaviors. Our data provide a circuit foundation to explore novel functional roles contributed by these noncanonical hippocampal circuit connections to hippocampal circuit dynamics and learning and memory behaviors.

Novelty promotes recognition memory persistence by D1 dopamine receptor and protein kinase A signalling in rat hippocampus.

Strategies for improving memory are increasingly studied, and exposure to a novel experience can be an efficient neuromodulator. Novelty effects on memory depend on D1-family dopamine receptors (D1Rs) activation. Here, we evaluated the novelty effect on memory persistence of Wistar rats and investigated the contribution of D1Rs and their signalling pathways by protein kinase A (PKA) and C (PKC). Animals with infusion cannulae inserted into the CA1 hippocampus area were trained on the novel object recognition (NOR) task, which involved exploring two different objects. After training, some rats received intrahippocampal infusions of vehicle or D1Rs agonist; others explored a novel environment for 5min and were infused with a variety of drugs targeting D1Rs and their signalling pathways. We demonstrated that pharmacological stimulation of D1Rs or novelty exposure promoted NOR memory persistence for 14 days and that the novelty effect depended on D1Rs activation. To determine if the D1 and D5 receptor subtypes were necessary for the impact of novelty exposure on memory, we blocked or stimulated PKA or PKC-protein kinases activated mainly by D1 and D5, respectively. Only PKA inhibition impaired the effect of novelty on memory persistence. After novelty and D1Rs blocking, PKA but not PKC stimulation maintained the memory persistence effect. Thus, we concluded that novelty promoted memory persistence by a mechanism-dependent on activating hippocampal D1Rs and PKA pathway.