Transient Receptor Potential Mucolipin-1 Participates in Intracerebral Hemorrhage-Induced Secondary Brain Injury by Inducing Neuroinflammation and Neuronal Cell Death
AbstractTransient receptor potential mucolipin-1 (TRPML1) is the most abundantly and widely expressed channel protein in the TRP family. While numerous studies have been conducted involving many aspects of TRPML1, such as its role in cell biology, oncology, and neurodegenerative diseases, there are limited reports about what role it plays in intracerebral hemorrhage (ICH)-induced secondary brain injury (SBI). Here we examined the function of TRPML1 in ICH-induced SBI. The caudal arterial blood of rats was injected into the caudate nucleus of basal ganglia to establish an experimental ICH model. We observed that lentivirus ...
Source: NeuroMolecular Medicine - February 4, 2023 Category: Neurology Source Type: research

α-Synuclein Induced the Occurrence of RBD via Interaction with OX1R and Modulated Its Degradation
AbstractRapid eye movement (REM) sleep behavior disorder (RBD) is a powerful early sign of Parkinson ’s disease (PD), but the pathogenetic mechanism involved in RBD remains largely unexplored. α-Synuclein has been verified to form Lewy bodies in the orexin neurons, whose activity and function rely on the orexin 1 receptor (OX1R). Dysfunction of the OX1R may induce the occurrence of RBD. Here, we determined the role of the interaction between α-Synuclein and OX1R in the pathogenesis of RBD, in vitro and in vivo. We found that injection of α-Synuclein into the lateral hypothalamus area (LHA) damaged orexin neurons and i...
Source: NeuroMolecular Medicine - January 23, 2023 Category: Neurology Source Type: research

CD33/TREM2 Signaling Mediates Sleep Deprivation-Induced Memory Impairment by Regulating Microglial Phagocytosis
This study provides novel evidence that activating CD33 and/or inhibiting TREM2 activity represent potential therapies for sleep loss-induced memory deficits through the modul ation of microglial phagocytosis. (Source: NeuroMolecular Medicine)
Source: NeuroMolecular Medicine - January 14, 2023 Category: Neurology Source Type: research

Involvement of Microbiome Gut –Brain Axis in Neuroprotective Effect of Quercetin in Mouse Model of Repeated Mild Traumatic Brain Injury
AbstractRepeated mild traumatic brain injury (rmTBI) poses adversity in the form of neurological deficits. The ignition of long-term neurological aberrations post-TBI is appended with the microbiota gut –brain axis perturbation. Herein, we examined whether quercetin, which is anti-inflammatory and antioxidant flavonoid, serves as a prebiotic and modifies the compromised microbiome gut–brain axis in rmTBI mouse model. Male C57BL/6 mice were subjected to rmTBI for 7 times. The quercetin (50 mg/k g) was administered peroral from the day1 of first injury till 7 days post-injury. The neurobehavioral assessments were perfo...
Source: NeuroMolecular Medicine - December 8, 2022 Category: Neurology Source Type: research

Neural Stem Cells Secretome Increased Neurogenesis and Behavioral Performance and the Activation of Wnt/ β-Catenin Signaling Pathway in Mouse Model of Alzheimer’s Disease
In this study, mice were randomly allocated into three different groups as follows: Control, AD + Vehicle, and AD + NSCs-CM groups. To induce mouse model of AD, A β1-42 was injected into intracerebroventricular region. Following AD-like confirmation through thioflavin S staining and Passive avoidance test, about 5 µl mouse NSCs-CM was injected into the target areas 21 days after AD induction. For evaluation of endogenous proliferation rate (BrdU/Nestin+ cells), 50  µg/kbW BrdU was intraperitoneally injected for 5 consecutive days. To track NSC differentiation, percent of BrdU/NeuN+ cells were monitored via im...
Source: NeuroMolecular Medicine - December 1, 2022 Category: Neurology Source Type: research

Tau and GSK-3 β are Critical Contributors to α-Synuclein-Mediated Post-Stroke Brain Damage
AbstractPost-stroke secondary brain damage is significantly influenced by the induction and accumulation of α-Synuclein (α-Syn). α-Syn-positive inclusions are often present in tauopathies and elevated tau levels and phosphorylation promotes neurodegeneration. Glycogen synthase kinase 3β (GSK-3β) is a known promoter of tau phosphorylation. We currently evaluated the interaction of α-Syn with GSK-3β and tau in post-ischemic mouse brain. Transient focal ischemia led to increased cerebral protein–protein interaction of α-Syn with both GSK-3β and tau and elevated tau phosphorylation. Treatment with a GSK-3β inhibito...
Source: NeuroMolecular Medicine - November 30, 2022 Category: Neurology Source Type: research

The Mood Stabilizer Lithium Slows Down Synaptic Vesicle Cycling at Glutamatergic Synapses
AbstractLithium is a mood stabilizer broadly used to prevent and treat symptoms of mania and depression in people with bipolar disorder (BD). Little is known, however, about its mode of action. Here, we analyzed the impact of lithium on synaptic vesicle (SV) cycling at presynaptic terminals releasing glutamate, a neurotransmitter previously implicated in BD and other neuropsychiatric conditions. We used the pHluorin-based synaptic tracer vGpH and a fully automated image processing pipeline to quantify the effect of lithium on both SV exocytosis and endocytosis in hippocampal neurons. We found that lithium selectively reduc...
Source: NeuroMolecular Medicine - November 27, 2022 Category: Neurology Source Type: research

SS-31 Improves Cognitive Function in Sepsis-Associated Encephalopathy by Inhibiting the Drp1-NLRP3 Inflammasome Activation
In this study, we aimed at exploring the effects of mitochondrial-targeted antioxidant peptide SS-31 on cognitive function in mice with SAE. In mice, SS-31 was intraperitoneally administered for seven consecutive days after cecal ligation and puncture surgery. SS-31 improved cognitive performance and survival rate of mice and alleviated hippocampal inflammation, reactive oxygen species production, and excessive mitochondrial fission. The increase of nucleotide-binding oligomerization domain 3 (NLRP3) and phosphorylated dynamin-related protein 1 (Drp1) ser616 in microglia was attenuated by SS-31. In vitro, the microglial ce...
Source: NeuroMolecular Medicine - November 4, 2022 Category: Neurology Source Type: research