Specific connectivity optimizes learning in thalamocortical loops.

Thalamocortical loops have a central role in cognition and motor control, but precisely how they contribute to these processes is unclear. Recent studies showing evidence of plasticity in thalamocortical synapses indicate a role for the thalamus in shaping cortical dynamics through learning. Since signals undergo a compression from the cortex to the thalamus, we hypothesized that the computational role of the thalamus depends critically on the structure of corticothalamic connectivity. To test this, we identified the optimal corticothalamic structure that promotes biologically plausible learning in thalamocortical synapses. We found that corticothalamic projections specialized to communicate an efference copy of the cortical output benefit motor control, while communicating the modes of highest variance is optimal for working memory tasks. We analyzed neural recordings from mice performing grasping and delayed discrimination tasks and found corticothalamic communication consistent with these predictions. These results suggest that the thalamus orchestrates cortical dynamics in a functionally precise manner through structured connectivity.

Lycium Barbarum Polysaccharides Improves Cognitive Functions in ICV-STZ-Induced Alzheimer's Disease Mice Model by Improving the Synaptic Structural Plasticity and Regulating IRS1/PI3K/AKT Signaling Pathway.

Lycium barbarum polysaccharide (LBP) have a certain curative effect on hypoglycemic and neuroprotective effects, but the specific mechanism is unclear and needs to be further explored. This study aimed to clarify the mechanisms of LBP in the treatment of ICV-STZ mice model of AD from the perspectives of insulin resistance, IRS1/PI3K/AKT signaling pathway, and synaptic protein expression. We used male C57BL/6J mice injected with STZ (3 mg/kg) in the lateral ventricle as an AD model. After treatment with LBP, the learning and memory abilities of ICV-STZ mice were enhanced, and the pathological changes in brain tissue were alleviated. LBP can regulate the expression of proteins related to the IRS1/PI3K/AKT signaling pathway and thereby reducing Aß deposition and tau protein phosphorylation in the brain of ICV-STZ mice. In addition, LBP also can up-regulate the expression of synaptic proteins. The results indicated that LBP played a neuroprotective role by regulating the IRS1/PI3K/AKT pathway, inhibiting tau protein hyperphosphorylation and improving the expression levels of synapse-related proteins.

Deciphering the antidepressant effects of Rosa damascena essential oil mediated through the serotonergic synapse signaling pathway.

ETHNOPHARMACOLOGICAL RELEVANCE: Rosa damascena is an ancient plant with significance in both medicine and perfumery that have a variety of therapeutic properties, including antidepressant, anti-anxiety, and anti-stress effects. Rose damascena essential oil (REO) has been used to treat depression, anxiety and other neurological related disorders in Iranian traditional medicine. However, its precise mechanism of action remains elusive. AIM OF THE STUDY: The aim of this study was to investigate the impact and mechanism underlying the influence of REO on chronic unpredictable mild stress (CUMS) rats. MATERIALS AND METHODS: Gas chromatography-mass spectrometry (GC-MS) technique coupling was used to analyze of the components of REO. A CUMS rat model was replicated to assess the antidepressant effects of varying doses of REO. This assessment encompassed behavioral evaluations, biochemical index measurements, and hematoxylin-eosin staining. For a comprehensive analysis of hippocampal tissues, we employed transcriptomics and incorporated weighting coefficients by means of network pharmacology. These measures allowed us to explore differentially expressed genes and biofunctional pathways affected by REO in the context of depression treatment. Furthermore, GC-MS metabolomics was employed to assess metabolic profiles, while a joint analysis in Metscape facilitated the construction of a network elucidating the links between differentially expressed genes and metabolites, thereby elucidating potential relationships and clarifying key pathways regulated by REO. Finally, the expression of relevant proteins in the key pathways was determined through immunohistochemistry and Western blot analysis. Molecular docking was utilized to investigate the interactions between active components and key targets, thereby validating the experimental results. RESULTS: REO alleviated depressive-like behavior, significantly elevated levels of the neurotransmitter 5-hydroxytryptamine (5-HT), and reduced hippocampal neuronal damage in CUMS rats. This therapeutic effect may be associated with the modulation of the serotonergic synapse signaling pathway. Furthermore, REO rectified metabolic disturbances, primarily through the regulation of amino acid metabolic pathways. Joint analysis revealed five differentially expressed genes (EEF1A1, LOC729197, ATP8A2, NDST4, and GAD2), suggesting their potential in alleviating depressive symptoms by modulating the serotonergic synapse signaling pathway and tryptophan metabolism. REO also modulated the 5-HT2A-mediated extracellular regulated protein kinases-cAMP-response element binding protein-brain-derived neurotrophic factor (ERK-CREB-BDNF) pathway. In addition, molecular docking results indicated that citronellol, geraniol and (E,E)-farnesol in REO may serve as key active ingredients responsible for its antidepressant effects. CONCLUSIONS: This study is the first to report that REO can effectively alleviate CUMS-induced depression-like effects in rats. Additionally, the study offers a comprehensive understanding of its intricate antidepressant mechanism from a multi-omics and multi-level perspective. Our findings hold promise for the clinical application and further development of this essential oil.

Cortical cell assemblies and their underlying connectivity: An in silico study.

Recent developments in experimental techniques have enabled simultaneous recordings from thousands of neurons, enabling the study of functional cell assemblies. However, determining the patterns of synaptic connectivity giving rise to these assemblies remains challenging. To address this, we developed a complementary, simulation-based approach, using a detailed, large-scale cortical network model. Using a combination of established methods we detected functional cell assemblies from the stimulus-evoked spiking activity of 186,665 neurons. We studied how the structure of synaptic connectivity underlies assembly composition, quantifying the effects of thalamic innervation, recurrent connectivity, and the spatial arrangement of synapses on dendrites. We determined that these features reduce up to 30%, 22%, and 10% of the uncertainty of a neuron belonging to an assembly. The detected assemblies were activated in a stimulus-specific sequence and were grouped based on their position in the sequence. We found that the different groups were affected to different degrees by the structural features we considered. Additionally, connectivity was more predictive of assembly membership if its direction aligned with the temporal order of assembly activation, if it originated from strongly interconnected populations, and if synapses clustered on dendritic branches. In summary, reversing Hebb's postulate, we showed how cells that are wired together, fire together, quantifying how connectivity patterns interact to shape the emergence of assemblies. This includes a qualitative aspect of connectivity: not just the amount, but also the local structure matters; from the subcellular level in the form of dendritic clustering to the presence of specific network motifs.

The Interplay between Neurotransmitters and Calcium Dynamics in Retinal Synapses during Development, Health, and Disease.

The intricate functionality of the vertebrate retina relies on the interplay between neurotransmitter activity and calcium (Ca2+) dynamics, offering important insights into developmental processes, physiological functioning, and disease progression. Neurotransmitters orchestrate cellular processes to shape the behavior of the retina under diverse circumstances. Despite research to elucidate the roles of individual neurotransmitters in the visual system, there remains a gap in our understanding of the holistic integration of their interplay with Ca2+ dynamics in the broader context of neuronal development, health, and disease. To address this gap, the present review explores the mechanisms used by the neurotransmitters glutamate, gamma-aminobutyric acid (GABA), glycine, dopamine, and acetylcholine (ACh) and their interplay with Ca2+ dynamics. This conceptual outline is intended to inform and guide future research, underpinning novel therapeutic avenues for retinal-associated disorders.

Transcranial Low-Intensity Focused Ultrasound Stimulation of the Visual Thalamus Produces Long-Term Depression of Thalamocortical Synapses in the Adult Visual Cortex.

Transcranial focused ultrasound stimulation (tFUS) is a noninvasive neuromodulation technique, which can penetrate deeper and modulate neural activity with a greater spatial resolution (on the order of millimeters) than currently available noninvasive brain stimulation methods, such as transcranial magnetic stimulation (TMS) and transcranial direct current stimulation (tDCS). While there are several studies demonstrating the ability of tFUS to modulate neuronal activity, it is unclear whether it can be used for producing long-term plasticity as needed to modify circuit function, especially in adult brain circuits with limited plasticity such as the thalamocortical synapses. Here we demonstrate that transcranial low-intensity focused ultrasound (LIFU) stimulation of the visual thalamus (dorsal lateral geniculate nucleus, dLGN), a deep brain structure, leads to NMDA receptor (NMDAR)-dependent long-term depression of its synaptic transmission onto layer 4 neurons in the primary visual cortex (V1) of adult mice of both sexes. This change is not accompanied by large increases in neuronal activity, as visualized using the cFos Targeted Recombination in Active Populations (cFosTRAP2) mouse line, or activation of microglia, which was assessed with IBA-1 staining. Using a model (SONIC) based on the neuronal intramembrane cavitation excitation (NICE) theory of ultrasound neuromodulation, we find that the predicted activity pattern of dLGN neurons upon sonication is state-dependent with a range of activity that falls within the parameter space conducive for inducing long-term synaptic depression. Our results suggest that noninvasive transcranial LIFU stimulation has a potential for recovering long-term plasticity of thalamocortical synapses in the postcritical period adult brain.

Functionally Distinct Circuits Are Linked by Heterocellular Electrical Synapses in the Thalamic Reticular Nucleus.

The thalamic reticular nucleus (TRN) inhibits sensory thalamocortical relay neurons and is a key regulator of sensory attention as well as sleep and wake states. Recent developments have identified two distinct genetic subtypes of TRN neurons, calbindin-expressing (CB) and somatostatin-expressing (SOM) neurons. These subtypes differ in localization within the TRN, electrophysiological properties, and importantly, targeting of thalamocortical relay channels. CB neurons send inhibition to and receive excitation from first-order thalamic relay nuclei, while SOM neurons send inhibition to and receive excitation from higher-order thalamic areas. These differences create distinct channels of information flow. It is unknown whether TRN neurons form electrical synapses between SOM and CB neurons and consequently bridge first-order and higher-order thalamic channels. Here, we use GFP reporter mice to label and record from CB-expressing and SOM-expressing TRN neurons. We confirm that GFP expression properly differentiates TRN subtypes based on electrophysiological differences, and we identified electrical synapses between pairs of neurons with and without common GFP expression for both CB and SOM types. That is, electrical synapses link both within and across subtypes of neurons in the TRN, forming either homocellular or heterocellular synapses. Therefore, we conclude that electrical synapses within the TRN provide a substrate for functionally linking thalamocortical first-order and higher-order channels within the TRN.

Synaptic plasticity and the role of astrocytes in central metabolic circuits.

Neural circuits in the brain, primarily in the hypothalamus, are paramount to the homeostatic control of feeding and energy utilization. They integrate hunger, satiety, and body adiposity cues from the periphery and mediate the appropriate behavioral and physiological responses to satisfy the energy demands of the animal. Notably, perturbations in central homeostatic circuits have been linked to the etiology of excessive feeding and obesity. Considering the ever-changing energy requirements of the animal and required adaptations, it is not surprising that brain-feeding circuits remain plastic in adulthood and are subject to changes in synaptic strength as a consequence of nutritional status. Indeed, synapse density, probability of presynaptic transmitter release, and postsynaptic responses in hypothalamic energy balance centers are tailored to behavioral and physiological responses required to sustain survival. Mounting evidence supports key roles of astrocytes facilitating some of this plasticity. Here we discuss these synaptic plasticity mechanisms and the emerging roles of astrocytes influencing energy and glucose balance control in health and disease. This article is categorized under: Cancer > Molecular and Cellular Physiology Neurological Diseases > Molecular and Cellular Physiology.

Ventral posterolateral and ventral posteromedial thalamocortical neurons have distinct physiological properties.

Somatosensory information is propagated from the periphery to the cerebral cortex by two parallel pathways through the ventral posterolateral (VPL) and ventral posteromedial (VPM) thalamus. VPL and VPM neurons receive somatosensory signals from the body and head, respectively. VPL and VPM neurons may also receive cell type-specific GABAergic input from the reticular nucleus of the thalamus. Although VPL and VPM neurons have distinct connectivity and physiological roles, differences in their functional properties remain unclear as they are often studied as one ventrobasal thalamus neuron population. Here, we directly compared synaptic and intrinsic properties of VPL and VPM neurons in C57Bl/6J mice of both sexes aged P25-P32. VPL neurons showed greater depolarization-induced spike firing and spike frequency adaptation than VPM neurons. VPL and VPM neurons fired similar numbers of spikes during hyperpolarization rebound bursts, but VPM neurons exhibited shorter burst latency compared with VPL neurons, which correlated with larger sag potential. VPM neurons had larger membrane capacitance and more complex dendritic arbors. Recordings of spontaneous and evoked synaptic transmission suggested that VPL neurons receive stronger excitatory synaptic input, whereas inhibitory synapse strength was stronger in VPM neurons. This work indicates that VPL and VPM thalamocortical neurons have distinct intrinsic and synaptic properties. The observed functional differences could have important implications for their specific physiological and pathophysiological roles within the somatosensory thalamocortical network.NEW & NOTEWORTHY This study revealed that somatosensory thalamocortical neurons in the VPL and VPM have substantial differences in excitatory synaptic input and intrinsic firing properties. The distinct properties suggest that VPL and VPM neurons could process somatosensory information differently and have selective vulnerability to disease. This work improves our understanding of nucleus-specific neuron function in the thalamus and demonstrates the critical importance of studying these parallel somatosensory pathways separately.

Hybrid neuromorphic hardware with sparing 2D synapse and CMOS neuron for character recognition.

Neuromorphic computing enables efficient processing of data-intensive tasks, but requires numerous artificial synapses and neurons for certain functions, which leads to bulky systems and energy challenges. Achieving functionality with fewer synapses and neurons will facilitate integration density and computility. Two-dimensional (2D) materials exhibit potential for artificial synapses, including diverse biomimetic plasticity and efficient computing. Considering the complexity of neuron circuits and the maturity of complementary metal-oxide-semiconductor (CMOS), hybrid integration is attractive. Here, we demonstrate a hybrid neuromorphic hardware with 2D MoS2 synaptic arrays and CMOS neural circuitry integrated on board. With the joint benefit of hybrid integration, frequency coding and feature extraction, a total cost of twelve MoS2 synapses, three CMOS neurons, combined with digital/analogue converter enables alphabetic and numeric recognition. MoS2 synapses exhibit progressively tunable weight plasticity, CMOS neurons integrate and fire frequency-encoded spikes to display the target characters. The synapse- and neuron-saving hybrid hardware exhibits a competitive accuracy of 98.8% and single recognition energy consumption of 11.4 µW. This work provides a viable solution for building neuromorphic hardware with high compactness and computility.

Synaptic Origin of Early Sensory-evoked Oscillations in the Immature Thalamus.

During the critical period of postnatal development, brain maturation is extremely sensitive to external stimuli. Newborn rodents already have functional somatosensory pathways and the thalamus, but the cortex is still forming. Immature thalamic synapses may produce large postsynaptic potentials in immature neurons, while non-synaptic membrane currents remain relatively weak and slow. The thalamocortical system generates spontaneous and evoked early gamma and spindle-burst oscillations in newborn rodents. How relatively strong synapses and weak intrinsic currents interact with each other and how they contribute to early thalamic activities remains largely unknown. Here, we performed local field potential (LFP), juxtacellular, and patch-clamp recordings in the somatosensory thalamus of urethane-anesthetized rat pups at postnatal days 6-7 with one whisker stimulation. We removed the overlying cortex and hippocampus to reach the thalamus with electrodes. Deflection of only one (the principal) whisker induced spikes in a particular thalamic cell. Whisker deflection evoked a group of large-amplitude excitatory events, likely originating from lemniscal synapses and multiple inhibitory postsynaptic events in thalamocortical cells. Large-amplitude excitatory events produced a group of spike bursts and could evoke a depolarization block. Juxtacellular recordings confirmed the partial inactivation of spikes. Inhibitory events prevented inactivation of action potentials and gamma-modulated neuronal firing. We conclude that the interplay of strong excitatory and inhibitory synapses and relatively weak intrinsic currents produces sensory-evoked early gamma oscillations in thalamocortical cells. We also propose that sensory-evoked large-amplitude excitatory events contribute to evoked spindle-bursts.

Akkermansia muciniphila supplementation prevents cognitive impairment in sleep-deprived mice by modulating microglial engulfment of synapses.

The microbiome-gut-brain axis plays a crucial role in many neurological diseases, including mild cognitive impairment. Sleep deprivation (SD) induces cognitive decline accompanied by alterations in the gut microbiota. However, the role of gut microbiota alterations in SD-induced cognitive dysfunction and the underlying mechanisms remain unclear. Here, we found that dysbiosis of the gut microbiota following pretreatment with broad-spectrum antibiotics worsens SD-induced cognitive impairment in mice. Fecal microbiota transplantation from SD mice to healthy mice induced cognitive impairment. Additionally, the abundance of Akkermansia muciniphila (A. muciniphila) in the mouse gut microbiota was significantly reduced after 7 days of SD. A. muciniphila pretreatment alleviated cognitive dysfunction and prevented synaptic reduction in the hippocampus in SD mice. A. muciniphila pretreatment inhibited extensive microglial activation and synaptic engulfment in the hippocampus of SD mice. Metabolomics analysis revealed that A. muciniphila pretreatment increased the serum acetate and butanoic acid levels in SD mice. Finally, pretreatment with short-chain fatty acids (SCFAs) inhibited microglial synaptic engulfment and prevented neuronal synaptic loss in SD mice and primary microglia-neuron co-culture following LPS stimulation. Together, our findings illustrate that gut dysbiosis plays an essential role in SD-induced cognitive impairment by activating microglial engulfment at synapses. A. muciniphila supplementation may be a novel preventative strategy for SD-induced cognitive dysfunction, by increasing SCFAs production and maintaining microglial homeostasis.

Human Breast Milk microRNAs, Potential Players in the Regulation of Nervous System.

Human milk is the biological fluid with the highest exosome amount and is rich in microRNAs (miRNAs). These are key regulators of gene expression networks in both normal physiologic and disease contexts, miRNAs can influence many biological processes and have also shown promise as biomarkers for disease. One of the key aspects in the regeneration of the nervous system is that there are practically no molecules that can be used as potential drugs. In the first weeks of lactation, we know that human breast milk must contain the mechanisms to transmit molecular and biological information for brain development. For this reason, our objective is to identify new modulators of the nervous system that can be used to investigate neurodevelopmental functions based on miRNAs. To do this, we collected human breast milk samples according to the time of delivery and milk states: mature milk and colostrum at term; moderate and very preterm mature milk and colostrum; and late preterm mature milk. We extracted exosomes and miRNAs and realized the miRNA functional assays and target prediction. Our results demonstrate that miRNAs are abundant in human milk and likely play significant roles in neurodevelopment and normal function. We found 132 different miRNAs were identified across all samples. Sixty-nine miRNAs had significant differential expression after paired group comparison. These miRNAs are implicated in gene regulation of dopaminergic/glutamatergic synapses and neurotransmitter secretion and are related to the biological process that regulates neuron projection morphogenesis and synaptic vesicle transport. We observed differences according to the delivery time and with less clarity according to the milk type. Our data demonstrate that miRNAs are abundant in human milk and likely play significant roles in neurodevelopment and normal function.

Functional and structural synaptic remodeling mechanisms underlying somatotopic organization and reorganization in the thalamus.

The somatosensory system organizes the topographic representation of body maps, termed somatotopy, at all levels of an ascending hierarchy. Postnatal maturation of somatotopy establishes optimal somatosensation, whereas deafferentation in adults reorganizes somatotopy, which underlies pathological somatosensation, such as phantom pain and complex regional pain syndrome. Here, we focus on the mouse whisker somatosensory thalamus to study how sensory experience shapes the fine topography of afferent connectivity during the critical period and what mechanisms remodel it and drive a large-scale somatotopic reorganization after peripheral nerve injury. We will review our findings that, following peripheral nerve injury in adults, lemniscal afferent synapses onto thalamic neurons are remodeled back to immature configuration, as if the critical period reopens. The remodeling process is initiated with local activation of microglia in the brainstem somatosensory nucleus downstream to injured nerves and heterosynaptically controlled by input from GABAergic and cortical neurons to thalamic neurons. These fruits of thalamic studies complement well-studied cortical mechanisms of somatotopic organization and reorganization and unveil potential intervention points in treating pathological somatosensation.

Proglucagon signalling in the rat Dorsomedial Hypothalamus - Physiology and high-fat diet-mediated alterations.

A relatively new pharmacological target in obesity treatment has been the preproglucagon (PPG) signalling, predominantly with glucagon-like peptide (GLP) 1 receptor agonists. As far as the PPG role within the digestive system is well recognised, its actions in the brain remain understudied. Here, we investigated PPG signalling in the Dorsomedial Hypothalamus (DMH), a structure involved in feeding regulation and metabolism, using in situ hybridisation, electrophysiology, and immunohistochemistry. Our experiments were performed on animals fed both control, and high-fat diet (HFD), uncovering HFD-mediated alterations. First, sensitivity to exendin-4 (Exn4, a GLP1R agonist) was shown to increase under HFD, with a higher number of responsive neurons. The amplitude of the response to both Exn4 and oxyntomodulin (Oxm) was also altered, diminishing its relationship with the cells' spontaneous firing rate. Not only neuronal sensitivity, but also GLP1 presence, and therefore possibly release, was influenced by HFD. Immunofluorescent labelling of the GLP1 showed changes in its density depending on the metabolic state (fasted/fed), but this effect was eliminated by HFD feeding. Interestingly, these dietary differences were absent after a period of restricted feeding, allowing for an anticipation of the alternating metabolic states, which suggests possible prevention of such outcome.

Multiscale model of primary motor cortex circuits predicts in vivo cell-type-specific, behavioral state-dependent dynamics.

Understanding cortical function requires studying multiple scales: molecular, cellular, circuit, and behavioral. We develop a multiscale, biophysically detailed model of mouse primary motor cortex (M1) with over 10,000 neurons and 30 million synapses. Neuron types, densities, spatial distributions, morphologies, biophysics, connectivity, and dendritic synapse locations are constrained by experimental data. The model includes long-range inputs from seven thalamic and cortical regions and noradrenergic inputs. Connectivity depends on cell class and cortical depth at sublaminar resolution. The model accurately predicts in vivo layer- and cell-type-specific responses (firing rates and LFP) associated with behavioral states (quiet wakefulness and movement) and experimental manipulations (noradrenaline receptor blockade and thalamus inactivation). We generate mechanistic hypotheses underlying the observed activity and analyzed low-dimensional population latent dynamics. This quantitative theoretical framework can be used to integrate and interpret M1 experimental data and sheds light on the cell-type-specific multiscale dynamics associated with several experimental conditions and behaviors.

Synaptic and circuit mechanisms prevent detrimentally precise correlation in the developing mammalian visual system.

The developing visual thalamus and cortex extract positional information encoded in the correlated activity of retinal ganglion cells by synaptic plasticity, allowing for the refinement of connectivity. Here, we use a biophysical model of the visual thalamus during the initial visual circuit refinement period to explore the role of synaptic and circuit properties in the regulation of such neural correlations. We find that the NMDA receptor dominance, combined with weak recurrent excitation and inhibition characteristic of this age, prevents the emergence of spike-correlations between thalamocortical neurons on the millisecond timescale. Such precise correlations, which would emerge due to the broad, unrefined connections from the retina to the thalamus, reduce the spatial information contained by thalamic spikes, and therefore we term them 'parasitic' correlations. Our results suggest that developing synapses and circuits evolved mechanisms to compensate for such detrimental parasitic correlations arising from the unrefined and immature circuit.

Flexible Solution-Processable Black-Phosphorus-Based Optoelectronic Memristive Synapses for Neuromorphic Computing and Artificial Visual Perception Applications.

Being renowned for operating with visible-light pulses and electrical signals, optoelectronic memristive synaptic devices have excellent potential for neuromorphic computing systems and artificial visual information processing. Here, a flexible back-end-of-line-compatible optoelectronic memristor based on a solution-processable black phosphorus/HfOx bilayer with excellent synaptic features, toward biomimetic retinas is presented. The device shows highly stable synaptic features such as long-term potentiation (LTP) and long-term depression (LTD) for repetitive 1000 epochs, having 400 conductance pulses, each. The device presents advanced synaptic features in terms of long-term memory (LTM)/short term memory (STM), as well as learning-forgetting-relearning when visible light is induced on it. These advanced synaptic features can improve the information processing abilities for neuromorphic applications. Interestingly, the STM can be converted into LTM by adjusting the intensity of light and illumination time. Using the light-induced characteristics of the device, a 6 × 6 synaptic array is developed to exhibit possible use in artificial visual perception. Moreover, the devices are flexed using a silicon back-etching process. The resulting flexible devices demonstrate stable synaptic features when bent down to 1 cm radius. These multifunctional features in a single memristive cell make it highly suitable for optoelectronic memory storage, neuromorphic computing, and artificial visual perception applications.

Kidney Yang Deficiency Syndrome Exacerbates Aß25-35-Induced Pathological Changes, and Ginsenoside Re Ameliorates Synapse Lesions in Aß25-35- Injected Rats with Kidney Yang Deficiency Syndrome.

BACKGROUND: Traditional Chinese medicine (TCM) indicates that Alzheimer's disease (AD) is considered the consequence produced by Kidney Yang Deficiency Syndrome (KDS-Yang), which has similar clinical characteristics to glucocorticoid withdrawal syndrome. Ginsenoside Re (G-Re) has been found to ameliorate the symptoms and pathological impairments of AD. However, it's not clear whether G-Re could protect memory and synapse lesions against kidney deficiency dementia. METHODS: Subcutaneous injection of hydrocortisone for 14 days was used to produce KDS-Yang. On the 15th day, Aß25-35 peptide was injected into the intracerebroventricular (icv) of KDS-Yang rats. Spine density was analyzed by Golgi staining and the ultrastructural morphology of the synapse was detected using Transmission Electron Microscopy (TEM). Western blot was used to examine the expression of pS396, pS404, Tau-5, tGSK-3ß, pS9GSK-3ß, Syt, Syn I, GluA1, GluN2B, PSD93, PSD95, ß2-AR and pS346-b2-AR. RESULTS: Hyperphosphorylation of tau in Aß25-35-injected rats with KDS-Yang was stronger than in Aß25-35-injected rats at the sites of Ser396 and Ser404. G-Re improved spatial memory damage detected by Morris water-maze (MWM), enhanced spines density, the thickness of postsynaptic density (PSD) and increased the expression of Syt, Syn I, GluA1, GluN2B, PSD93 and PSD95. Moreover, GRe decreased the hyperphosphorylation of ß2-AR at serine 346 in Aß25-35-injected rats with KDS-Yang. CONCLUSION: KDS-Yang might exacerbate AD pathological lesions. Importantly, G-Re is a potential ingredient for protecting against memory and synapse deficits in kidney deficiency dementia.

Acupuncture inhibits autophagy and repairs synapses by activating the mTOR pathway in Parkinson's disease depression model rats.

Acupuncture is a good treatment for depression in Parkinson's disease (DPD), so the possible mechanism of acupuncture in the treatment of DPD was explored in this study. Firstly, observing the behavioral changes of the DPD rat model, the regulation of monoamine neurotransmitters dopamine (DA) and 5-hydroxytryptamine (5-HT) in the midbrain, the change of α-synuclein (α-syn) in the striatum, the efficacy of acupuncture in the treatment of DPD was discussed. Secondly, autophagy inhibitors and activators were selected to judge the effect of acupuncture on autophagy in the DPD rat model. Finally, an mTOR inhibitor was used to observe the effect of acupuncture on the mTOR pathway in the DPD rat model. The results showed that acupuncture could improve the motor and depressive symptoms of DPD model rats, increase the content of DA and 5-HT, and decrease the content of ɑ-syn in the striatum. Acupuncture inhibited the expression of autophagy in the striatum of DPD model rats. At the same time, acupuncture upregulates p-mTOR expression, inhibits autophagy, and promotes synaptic protein expression. Therefore, we concluded that acupuncture might improve the behavior of DPD model rats by activating the mTOR pathway, inhibiting autophagy from removing α-syn and repairing synapses.