Alzheimer's disease (AD) is a progressive neurodegenerative disorder with an impairment of cognition and memory. Current research on connectomics have now related changes in the network organization in AD to the patterns of accumulation and spread of amyloid and tau, providing insights into the neurobiological mechanisms of the disease. In addition, network analysis and modeling focus on particular use of graphs to provide intuition into key organizational principles of brain structure, that stipulate how neural activity propagates along structural connections. The utility of connectome-based computational models aids in early predicting, tracking the progression of biomarker-directed AD neuropathology. In this article, we present a short review of tau trajectory, the connectome changes in tau pathology, and the dependent recent connectome-based computational modelling approaches for tau spreading, reproducing pragmatic findings, and developing significant novel tau targeted therapies.

Ketamine, despite its efficacy in treating depression, raises concerns regarding safety due to potential abuse, cognitive impairment, and bladder toxicity. Ketamine can affect the locus coeruleus (LC) norepinephrine and attention networks. This study explored the protective effects of electroacupuncture (EA) on the LC of rats exposed to repeated administration of ketamine while investigating the potential role of the Calcium CaM-dependent protein kinase II (CAMK II)/ cAMP response element binding protein (CREB) pathway in mediating EA's impact on ketamine-induced neuronal injury in LC. Rats were repeatedly injected intraperitoneally with ketamine hydrochloride (50mg/kg) once daily for seven days. Subsequently, EA was performed at the acupoints "Zusanli" (ST36) and "Sanyinjiao" (SP-6) once daily following ketamine administration. The Morris water maze test was employed to assess behavioral changes in the rats. Neuronal injury was examined using Nissl staining, and the expression of CAMK II, CREB, and phospho-CREB (p-CREB) was evaluated through immunohistochemistry and western blotting. EA mitigated the cognitive and exploratory impairments and attenuated neuronal injury in the LC induced by repeated administration of ketamine. The expression of CAMK II and p-CREB proteins in the LC increased following 7 days of ketamine administration. However, EA treatment led to a downregulation of CAMK II and p-CREB expression. Repeated administration of ketamine in male rats can lead to neuronal injury and neurobehavioral dysfunction. However, EA was found to ameliorate neurodegeneration in the LC and enhance neurobehavioral symptoms. This therapeutic effect of EA may be attributed to its modulation of the CAMKII/CREB pathway, thereby mitigating the aforementioned adverse effects.

Alpha-pinene (α- pinene), an essential oil that falls under the category of monoterpenes, has various advantages. This research delves into the potential benefits of α-pinene in alleviating nociception caused by the formalin test and the molecular mechanisms involved. Alpha-pinene (1, 5, or 10mg/kg/day, i.p.) was administrated for 7 days before the formalin test. Observations of nociceptive behaviors were made during the formalin test. We examined the levels of TNF-α and IL-1β, as well as the expression of COX-1 in the spinal cord. Additionally, we evaluated the levels of TNF-α, IL-1β, SOD, GSH, CAT, and MDA in the skin of the hind paw that received a formalin injection. The peripheral injection of formalin triggered nociceptive behaviors, which was notably diminished by α-pinene 5 or 10mg/kg. The biochemical evaluation revealed that α-pinene significantly moderated the evaluation in TNF-α and IL-1β in the spinal cord induced by formalin injection. Additionally, it was found that α-pinene had a decreasing effect on the expression of COX-1 protein in the spinal cord. Also, α-pinene 5 or 10mg/kg caused a decrease of TNF-α, IL-1β, and MDA and an increase of SOD, GSH, and CAT at the formalin injection site. The study discovered that doses of 5 or 10mg/ml of α-pinene can effectively relieve nociceptive response in the formalin test. Alpha-pinene pretreatment reduced the presence of pro-inflammatory cytokines. It also improved the oxidative stress condition by enhancing antioxidant factors and reducing oxidant factors.

Depression is a series of symptoms that influence mood, thinking, and behavior and create unpleasant emotions like hopelessness and apathy. Treatment-resistant depression (TRD) affects 30% of depression patients despite the availability of several non-invasive therapies. Deep brain stimulation (DBS) is a novel therapy for TRD. The aim of the current study was to evaluate the effect of LHb-DBS by recording local field potentials (LFP) and conducting behavioral experiments. Thirty-two mature male Wistar rats were randomly divided into four groups: control, chronic mild stress (CMS), CMS+DBS, and DBS. After surgery and electrode placement in the lateral habenula (LHb), nucleus accumbens (NAc), and prelimbic cortex (PrL), the CMS protocol was applied for 3 weeks to create depression-like models. The open field test (OFT), sucrose preference test (SPT), and forced swim test (FST) were also performed. In the DBS groups, the LHb area was stimulated for four consecutive days. Finally, on the 22nd day, LFP was recorded from the NAc and PrL and analyzed using MATLAB software. Analyzing the findings using ANOVA and P-values ≤ 0.05 was considered. LHb-DBS alleviated depression-like behaviors in chronic moderate stress model rats (P≤0.05). Three weeks of CMS enhanced almost all band powers in the NAc, while LHb-DBS decreased the power of the theta, alpha, beta, and gamma bands in the NAc (P≤0.05), and the low-gamma band in the PrL. CMS also boosted the NAc-PrL coherence in low-frequency bands, while LHb-DBS increased beta and low gamma band coherence (P≤0.05). In sum, the results of the present study showed that depression enhances low-frequency coherence between NAc and PrL cortex. Depression also potentiates many brain oscillations in the NAc, which can be mainly reversed by LHb-DBS.

Stellaria dichotoma L. var. lanceolata Bge. is renowned for its efficacy in "clearing deficiency heat" and represents a significant traditional Chinese medicine (TCM) resource. Modern pharmacology has demonstrated the anti-anxiety effects of Stellaria dichotomaL. var.lanceolataBge. polysaccharides (SDPs). SDPs are one of the active constituents of Stellaria dichotoma L. var. lanceolata Bge. This study presents the first extraction of SDPs and investigates their potential molecular mechanisms and anxiolytic effects that are not previously reported. First, SDPs were obtained by water extraction and alcohol precipitation and analyzed for their monosaccharide composition by high performance liquid chromatography (HPLC). Male SD rats were subjected to a two-week indeterminate empty bottle stress procedure and a three-day acute restraint stress procedure, during which diazepam (DZP) (1mg/kg) and SDPs (50, 100 and 200mg/kg, intragastrically) were administered. A number of behavioral tests, including the elevated plus maze test (EPM), the open field test (OFT) and the light/dark box test (LDB), were used to assess the anti-anxiety potential of SDPs. Serum levels of Corticosterone (CORT) and Adrenocorticotropic hormone (ACTH), as well as the levels of Dopamine (DA) and serotonin (5-HT) found in the hippocampus and frontal cortex, were quantified using commercially available enzyme-linked immunosorbent assay (ELISA) kits. In addition, protein levels of key proteins cAMP-response element binding protein (CREB), phospho-CREB (p-CREB), brain-derived neurotrophic factor (BDNF), ERK½, p-ERK½, and GAPDH expression in rat hippocampus were measured by Western blot analysis, and modulation of the endocannabinoid system was assessed by immunohistochemistry. Following administration of SDPs (50, 100, 200mg/kg) and diazepam 1mg/kg, anxiolytic activity was exhibited through an increase in the percentage of arm opening times and arm opening time of rats in the elevated plus maze. Additionally, there was an increase in the number of times and time spent in the open field center, percentage of time spent in the open box, and shuttle times in the LDB. Furthermore, tissue levels of DA and 5-HT were increased in the hippocampus and frontal cortex of rats after treatment with SDPs. In addition, SDPs significantly decreased serum levels of CORT and ACTH in rats. SDPs also effectively regulated the phosphorylation of the extracellular regulated protein kinases (ERK) and CREB-BDNF pathway in the hippocampus. Moreover, the expression levels of CB1 and CB2 proteins were heightened due to SDPs treatment in rats. The study verified that SDPs alleviate anxiety in the EBS and ARS. The neuroregulatory behavior is accomplished by regulating the Monoamine neurotransmitter, HPA axis, and ECB-ERK-CREB-BDNF signaling pathway.

The deposition of amyloid β peptide (Aβ) is one of the main pathological features of AD. The much-talked sensory gamma entrainment may be a new treatment for Aβ load. Here we reviewed the generation and clearance pathways of Aβ, aberrant gamma oscillation in AD, and the therapeutic effect of sensory gamma entrainment on AD. In addition, we discuss these results based on stimulus parameters and possible potential mechanisms. This provides the support for sensory gamma entrainment targeting Aβ to improve AD.

The locus coeruleus (LC), a small subcortical structure in the brainstem, is the brain's principal source of norepinephrine. It plays a primary role in regulating stress, the sleep-wake cycle, and attention, and its degradation is associated with aging and neurodegenerative diseases associated with cognitive deficits (e.g., Parkinson's, Alzheimer's). Yet precisely how norepinephrine drives brain networks to support healthy cognitive function remains poorly understood - partly because LC's small size makes it difficult to study noninvasively in humans. Here, we characterized LC's influence on brain dynamics using a hidden Markov model fitted to functional neuroimaging data from healthy young adults across four attention-related brain networks and LC. We modulated LC activity using a behavioral paradigm and measured individual differences in LC magnetization transfer contrast. The model revealed five hidden states, including a stable state dominated by salience-network activity that occurred when subjects actively engaged with the task. LC magnetization transfer contrast correlated with this state's stability across experimental manipulations and with subjects' propensity to enter into and remain in this state. These results provide new insight into LC's role in driving spatiotemporal neural patterns associated with attention, and demonstrate that variation in LC integrity can explain individual differences in these patterns even in healthy young adults.

Xenin is a 25-amino acid peptide identified in human gastric mucosa, which is widely expressed in peripheral and central tissues. It is known that the central or peripheral administration of xenin decreases food intake in rodents. Nesfatin-1/NUCB2 (nesfatin-1) has been identified as an anorexic neuropeptide, it is often found co-localized with many peptides in the central nervous system. After the intracerebroventricular administration of xenin on nesfain-1-like immunoreactivity (LI) neurons, we examined its effects on food intake and water intake in rats. As a result, Fos-LI neurons were observed in the organum vasculosum of the laminae terminalis (OVLT), the median preoptic nucleus (MnPO), the subfornical organ (SFO), the supraoptic nucleus (SON), the paraventricular nucleus (PVN), the arcuate nucleus (Arc), the lateral hypothalamic area (LHA), the central amygdaloid nucleus (CAN), the dorsal raphe nucleus (DR), the locus coeruleus (LC), the area postrema (AP) and the nucleus of the solitary tract (NTS). After the administration, the number of Fos-LI neurons was significantly increased in the LC and the OVLT, the MnPO, the SFO, the SON, the PVN, the Arc, the LHA, the CAN, the DR, the AP and the NTS, compared with the control group. After the administration of xenin, we conducted double immunohistochemistry for Fos and nesfatin-1, and found that the number of nesfatin-1-LI neurons expressing Fos were significantly increased in the SON, the PVN, the Arc, the LHA, the CAN, the DR, the AP and the NTS, compared with the control group. The pretreatment of nesfatin-1 antisense significantly attenuated this xenin-induced feeding suppression, while that of nesfatin-1 missense showed no improvement. These results indicate that central administered xenin may have anorexia effects associated with activated central nesfatin-1 neurons.

Oxytocin (OXT) is secreted in a large amount during the middle and late pregnancy. Except for the regulation of functions related to childbirth, OXT is involved in the regulation of cognition, social behavior, addiction, pain and so on. Our aim is to confirm the increase of OXT content in mice in late pregnancy is the main cause of itch during pregnancy and observe whether exogenously administered OXT can induce or increase itch sensitivity. The research shows that itch sensitivity of mice increased significantly in late pregnancy and basically returned to normal one day after delivery. The number of OXT-positive neurons in paraventricular nucleus (PVN) and the content of OXT in serum of the late pregnant mice increased significantly, and decreased sharply after delivery. Intradermal injection of low concentration of OXT (0.2 nmol/L) could not induce scratching behavior in mice, but high concentration of OXT (5 nmol/L, 10 nmol/L) could do this in a dose-dependent manner. Low concentration of OXT significantly increased the itch sensitivity to histamine. Intradermal injection of oxytocin receptor (OXTR) or arginine vasopressin-1a receptor (AVPR1A) antagonist did not affect histamine-induced scratching behavior, but both reversed the increase of itch sensitivity in late pregnant mice or the facilitated itch sensitivity by OXT. Study suggests that both endogenous and exogenous increases in OXT can increase the body's sensitivity to itch, and even induce itch directly. Pruritus during pregnancy is closely related to the increase of OXT content in vivo. In the periphery, the itch-promoting effect of OXT is mediated by OXTR and AVPR1A.

Psychiatric disorders are common in patients with allergic asthma, and they can have a significant impact on their quality of life and disease control. Recent studies have suggested that there may be potential immune-brain communication mechanisms in asthma, which can activate inflammatory responses in different brain areas, leading to structural and functional alterations and behavioral changes. However, the precise mechanisms underlying these alterations remain unclear. In this paper, we comprehensively review the relevant research on asthma-induced brain structural and functional alterations that lead to the initiation and promotion of anxiety. We summarize the possible pathways for peripheral inflammation to affect the brain's structure and function. Our review highlights the importance of addressing neuropsychiatric disorders in the clinical guidelines of asthma, to improve the quality of life of these patients. We suggest that a better understanding of the mechanisms underlying psychiatric comorbidities in asthma could lead to the development of more effective treatments for these patients.