Prophylactic Effects of n-Acethylcysteine on Inflammation-induced Depression-like Behaviors in Mice.

Depression, affecting individuals worldwide, is a prevalent mental disease, with an increasing incidence. Numerous studies have been conducted on depression, yet its pathogenesis remains elusive. Recent advancements in research indicate that disturbances in synaptic transmission, synaptic plasticity, and reduced neurotrophic factor expression significantly contribute to depression's pathogenesis. In our study, we utilized adult male C57BL/6J mice. Lipopolysaccharide (LPS) can induce both chronic and acute depression-like symptoms in mice, a widely used model for studying depression associated with inflammation. N-acetylcysteine (NAC) exhibits anti-inflammatory and ameliorative effects on depressive symptoms. This study sought to determine whether NAC use could mitigate inflammatory depressive behavior through the enhancement of synaptic transmission, synaptic plasticity, and increasing levels of brain-derived neurotrophic factor (BDNF). In this study, we discovered that in mice modeled with depression-like symptoms, the expression levels of dendrites, BDNF, and miniature excitatory postsynaptic potential (mEPSC) in glutamatergic neurons, as well as the α-amino-3-hydroxy-5-methylisoxazole-4-propionic acid glutamate receptors (AMPARs) GluA1 and GluA2 subunits, were significantly decreased. These findings suggest an impairment in the synaptic transmission of glutamatergic neurons. Following treatment with NAC, the previously mentioned levels improved, indicating an enhancement in both synaptic transmission and synaptic plasticity. Our results suggest that NAC exerts a protective effect on mouse models of inflammatory depression, potentially through the enhancement of synaptic transmission and plasticity, as well as the restoration of neurotrophic factor expression. These findings offer vital animal experimental evidence supporting NAC's role in mitigating inflammatory depressive behaviors.

Neuropathic pain following spinal cord hemisection induced by the reorganization in primary somatosensory cortex and regulated by neuronal activity of lateral parabrachial nucleus.

AIMS: Neuropathic pain after spinal cord injury (SCI) remains a common and thorny problem, influencing the life quality severely. This study aimed to elucidate the reorganization of the primary sensory cortex (S1) and the regulatory mechanism of the lateral parabrachial nucleus (lPBN) in the presence of allodynia or hyperalgesia after left spinal cord hemisection injury (LHS). METHODS: Through behavioral tests, we first identified mechanical allodynia and thermal hyperalgesia following LHS. We then applied two-photon microscopy to observe calcium activity in S1 during mechanical or thermal stimulation and long-term spontaneous calcium activity after LHS. By slice patch clamp recording, the electrophysiological characteristics of neurons in lPBN were explored. Finally, exploiting chemogenetic activation or inhibition of the neurons in lPBN, allodynia or hyperalgesia was regulated. RESULTS: The calcium activity in left S1 was increased during mechanical stimulation of right hind limb and thermal stimulation of tail, whereas in right S1 it was increased only with thermal stimulation of tail. The spontaneous calcium activity in right S1 changed more dramatically than that in left S1 after LHS. The lPBN was also activated after LHS, and exploiting chemogenetic activation or inhibition of the neurons in lPBN could induce or alleviate allodynia and hyperalgesia in central neuropathic pain. CONCLUSION: The neuronal activity changes in S1 are closely related to limb pain, which has accurate anatomical correspondence. After LHS, the spontaneously increased functional connectivity of calcium transient in left S1 is likely causing the mechanical allodynia in right hind limb and increased neuronal activity in bilateral S1 may induce thermal hyperalgesia in tail. This state of allodynia and hyperalgesia can be regulated by lPBN.

Effects of sleep deprivation of various durations on novelty-related object recognition memory and object location memory in mice.

Sleep is essential for important physiological functions. Impairment of learning and memory function caused by lack of sleep is a common physiological phenomenon of which underlying changes in synaptic plasticity in the hippocampus are not well understood. The possible different effects of sleep deprivation (SD) lasting for various durations on learning and memory function and hippocampal synaptic plasticity are still not completely clear. In this study, we used a modified multiple platform method (MMPM) to induce rapid eye movement SD (REM SD), lasting for 24 h, 48 h, and 72 h, separately. The novel place recognition (NPR) and novel object recognition (NOR) tasks were used to test the novelty-related object recognition memory (ORM) and object location memory (OLM) of mice. Then, hippocampal synaptic plasticity was evaluated after all behavioural experiments. The results showed that REM SD played a key role in OLM but not in ORM. Specifically, 24 h REM SD improved novelty-related OLM, accompanied by a significantly increased hippocampal synaptic plasticity, including gain of dendritic spines, increased expression of hippocampal GluA1, and enhanced long-term potentiation (LTP), whereas 48 h REM SD showed no effect on OLM or the hippocampal synaptic plasticity mentioned above; however, 72 h REM SD impaired novelty-related OLM and weakened hippocampal synaptic plasticity, including serious loss of dendritic spines, decreased expression of hippocampal GluA1, and significantly attenuated LTP. Our results suggest that REM SD of various durations has different effects on both novelty-related OLM and hippocampal synaptic plasticity.

MicroRNA-20b-5p aggravates neuronal apoptosis induced by ß-Amyloid via down-regulation of Ras homolog family member C in Alzheimer's disease.

Recent studies have reported that microRNAs are abnormally expressed in brain tissues of Alzheimers disease (AD) patients. However, the accurate function of miR-20b-5p in AD has not been elucidated. We intended to investigate the role and underlying mechanism of miR-20b-5p in AD. The expression of miR-20b-5p was increased, and the expression of RhoC was decreased in the hippocampus of Appswe/PS△E 9 mice. In order to construct a cell model in vitro to study the underlying action mechanism, PC12 cells were treated with Aß25-35. The cell apoptosis detected by flow cytometry and the expression of cleaved-caspase-3 detected by western blot were both remarkably increased in PC12 cells treated with Aß25-35, but they were reduced by miR-20b-5p inhibitor. In addition, MTT test showed that the cell survival rate in Aß25-35 + miR-20b-5p inhibitor group was higher than that in Aß25-35 + NC inhibitor group. Double luciferase reporter gene analysis confirmed that the binding site of miR-20b-5p was in 3'- UTR of RhoC mRNA. Knockdown of RhoC increased neuronal apoptosis induced by Aß25-35 and the expression of cleaved-caspase-3, while miR-20b-5p inhibitor reversed these effects. Knockdown of RhoC aggravated the inhibition effect on cell viability induced by Aß25-35, while miR-20b-5p inhibitor diminished these effects. In conclusion, inhibition of miR-20b-5p attenuates apoptosis induced by Aß25-35 in PC12 cells through targeting RhoC. Therefore, miR-20b-5p may be a perspective curative target for AD.

Simultaneous calcium recordings of hippocampal CA1 and primary motor cortex M1 and their relations to behavioral activities in freely moving epileptic mice.

Epilepsy is a common neurological disorder characterized by recurrent epileptic seizures. The cause of most cases of epilepsy is unknown. Although changes of calcium events in a single brain region during seizures have been reported before, there have been few studies on relations between calcium events of two different brain regions and epileptic behaviors in freely moving mice. To analyze calcium events simultaneously recorded in hippocampal CA1 (CA1) and primary motor cortex M1 (M1), and to explore their relations to various epileptic behaviors in freely moving epileptic models. Epileptic models were induced by Kainic acid (KA), a direct agonist of glutamatergic receptor, on adult male C57/BL6J mice. Calcium events of neurons and glia in CA1 and M1 labeled by a calcium indicator dye were recorded simultaneously with a multi-channel fiber photometry system. Three typical types of calcium events associated with KA-induced seizures were observed, including calcium baseline-rising, cortical spreading depression (CSD) and calcium flashing with a steady rate. Our results showed that the calcium baseline-rising occurred in CA1 was synchronized with that in M1, but the CSD waves were not. However, synchronization of calcium flashing in the two areas was uncertain, because it was only detected in CA1. We also observed that different calcium events happened with different epileptic behaviors. Baseline-rising events were accompanied by clonus of forelimbs or trembling, CSD waves were closely related to head movements (15 out of 18, 6 mice). Calcium flashing occurred definitely with drastic convulsive motor seizures (CMS, 6 mice). The results prove that the synchronization of calcium event exists in CA1 and M1, and different calcium events are related with different seizure behaviors. Our results suggest that calcium events involve in the synchronization of neural network and behaviors in epilepsy.