Developmental Neurobiology最新文献

Inflammasomes, particularly the NLRP3 inflammasome, play a pivotal role in mediating neuroinflammation in neurodegenerative diseases such as Alzheimer's disease (AD), Parkinson's disease (PD), amyotrophic lateral sclerosis (ALS), multiple sclerosis (MS), and Huntington's disease (HD). Recent findings indicate that the activation of the NLRP3 inflammasome in microglia and astrocytes triggers the release of pro-inflammatory cytokines, including IL-1β and IL-18, which contribute to chronic inflammation and neuronal damage. This process accelerates neurodegeneration and exacerbates disease progression. Misfolded protein aggregates, mitochondrial dysfunction, and oxidative stress are key factors in the pathological activation of the NLRP3 inflammasome in these diseases. Recent studies have highlighted that targeting the NLRP3 inflammasome, either through direct inhibitors like MCC950 or natural compounds such as oridonin and β-hydroxybutyrate, shows promise in mitigating neuroinflammation and protecting neuronal integrity. These inhibitors have demonstrated neuroprotective effects in animal models of AD, PD, and MS, presenting a new therapeutic approach for halting disease progression. However, the complexity of NLRP3 regulation requires further investigation to balance its inflammatory and protective roles. This review examines the recent advancements in NLRP3 inflammasome research and discusses potential strategies for modulating inflammasome activity to slow or prevent the progression of neurodegenerative diseases.

Maternal stress and disruptions of the maternal microbiome during development can have profound organizational effects on the brain and behavior of offspring. We have previously demonstrated that these manipulations have marked, sex-dependent effects on aggressive behavior in Siberian hamsters, Phodopus sungorus. Given that the prelimbic cortex is sensitive to stress and may play a role in modulating social behaviors, here we investigated how maternal stress and disruption of the microbiome during pregnancy may affect the development of the prelimbic cortex in offspring. Pregnant hamsters were exposed to either a broad-spectrum antibiotic, social stress, combined treatments, or no manipulation (i.e., control). Adult offspring (PND 107–115) were euthanized, brains were stained using Golgi histology, and apical and basilar dendritic lengths of pyramidal cells in the prelimbic cortex were quantified. Our data indicate that maternal stress and microbiome manipulation have a sex-dependent effect on offspring dendritic morphology. Maternal stress increased apical dendritic length in female but not male offspring relative to controls. However, the combination of maternal stress and maternal antibiotics ameliorated the effect of stress alone. Thus, maternal stress and disruption of the microbiome interact to produce lasting changes in the prefrontal cortex of female offspring. Such changes may contribute to the behavioral effects of these manipulations.

Autism spectrum disorder (ASD) is characterized by persistent problems in speech, social interaction, restricted and repetitive behavior patterns, lack of interest, and intellectual disabilities. Currently, there is no effective treatment available for the core symptoms of ASD. Among various treatments, herbal pharmacological treatments have shown promising results with fewer side effects, especially cannabidiol (CBD) treatment for the core symptoms and co-morbidities of ASD. The current study was performed to explore the therapeutic potential of CBD oil supplementation against the valproic acid (VPA)-induced autism mouse model. The autism mouse model was developed by exposing albino BALB/c mouse fetuses to VPA (600 mg/kg) on gestational day 13. On postnatal day (PND)-21, the male pups from both control and diseased groups were further divided into the following treatment groups: (I) control saline group, (II) VPA-exposed group, (III) VPA + CBD oil (100 mg/kg/day/orally) group, and (IV) standard group of VPA + risperidone (RISP) (0.5 mg/kg/day/orally) for 3 consecutive weeks. VPA mice displayed autistic behaviors upon delivery, such as increased anxiety levels, delayed response to painful stimuli, and impaired social interaction. VPA mice also showed depletion of glutathione and other antioxidant levels. CBD oil improved these dysfunctions, as seen through biochemical analysis and morphological staining of the hippocampal region, prefrontal cortex, and Purkinje cells. These findings showed that CBD oil treatment significantly improved behavioral abnormalities and lowered the oxidative stress in the autistic mouse model by acting as an antioxidant.

The retinotectal projection, the direct synapse between retinal ganglion cells (RGCs) of the eye and tectal neurons of the optic tectum, is a major component of the amphibian visual system. A model of circuit formation, this projection has been studied in detail. There are, however, other retinorecipient targets that also comprise the amphibian visual system such as the pretectum and ventral midbrain tegmentum. Understanding how these other components of the visual system form and function will lead to a more comprehensive understanding of how the visual system, as a whole, assembles and functions. Toward this aim, here we describe the functional development of the Xenopus tadpole accessory optic system (AOS), a direct synaptic connection between RGC axons and the basal optic nucleus of the midbrain tegmentum. The AOS is highly conserved across vertebrates. It functions as the sensory side of the optokinetic and optomotor reflexes, compensatory eye and body movements, respectively, that stabilize the visual scene as the organism moves through it. Using an isolated brain preparation and whole-cell electrophysiological approaches, we compared the development of the AOS and retinotectal projection. We found that these two retinofugal projections display distinct developmental programs, which appear to mirror their different functions. Retinotectal synapses moved through a dynamic phase of previously described NMDA receptor-dependent refinement, a process that is known to sharpen the retinotopic map and thereby visual acuity. In contrast, the AOS synapse appeared more stable and activity independent across development, indicative of a hardwired circuit, built to support reflexive optic behaviors.

Major depressive disorder (MDD) is a common neuropsychiatric disorder with persistent low mood, feelings of weakness, and a lack of interestin daily tasks. Histamine N-methyltransferase (HNMT) protein is involved in the inactivation process of histamine in human physiology. Here, we aimed to assess the role of HNMT in the pathophysiology and development of MDD. This case–control study included 56 MDD patients and 32 healthy controls (HCs) by matching age, sex, body mass index (BMI), and other sociodemographic characteristics. A clinical psychiatrist assessed the MDD patients and HCs according to the DSM-5 criteria. We used the Ham-D scale in evaluating the severity of depressive symptoms. We used ELISA kits to estimate serum HNMT levels. We observed elevated serum HNMT concentration in MDD patients (29.25 ± 5.34 pg/ml) compared with HCs (23.13 ± 2.10 pg/ml). Serum HNMT levels and Ham-D scores are positively correlated with each other in MDD patients (r = 0.632, p < 0.001). Also, the receiver operating characteristic curve analysis illustrated a significant diagnostic value for HNMT with the area under the curve (AUC = 0.916) at p < 0.001. The promising findings from this study anticipate that the elevated serum levels of HNMT may be associated with the pathophysiology and mechanism of MDD. We recommend further interventional studies to produce more precise and accurate results on this biomarker in depression.