Microglia-dependent excessive synaptic pruning leads to cortical underconnectivity and behavioral abnormality following chronic social defeat stress in mice.

Synapse loss in medial prefrontal cortex (mPFC) has been implicated in stress-related mood disorders, such as depression. However, the exact effect of synapse elimination in the depression and how it is triggered are largely unknown. Through repeated longitudinal imaging of mPFC in the living brain, we found both presynaptic and postsynaptic components were declined, together with the impairment of synapse remodeling and cross-synaptic signal transmission in the mPFC during chronic stress. Meanwhile, chronic stress also induced excessive microglia phagocytosis, leading to engulfment of excitatory synapses. Further investigation revealed that the elevated complement C3 during the stress acted as the tag of synapses to be eliminated by microglia. Besides, chronic stress induced a reduction of the connectivity between the mPFC and neighbor regions. C3 knockout mice displayed significant reduction of synaptic pruning and alleviation of disrupted functional connectivity in mPFC, resulting in more resilience to chronic stress. These results indicate that complement-mediated excessive microglia phagocytosis in adulthood induces synaptic dysfunction and cortical hypo-connectivity, leading to stress-related behavioral abnormality.

Long noncoding RNA Gm2694 drives depressive-like behaviors in male mice by interacting with GRP78 to disrupt endoplasmic reticulum homeostasis.

Long noncoding RNAs (lncRNAs) are involved in various biological processes and implicated in the regulation of neuronal activity, but the potential role of lncRNAs in depression remains largely unknown. Here, we identified that lncRNA Gm2694 was increased in the medial prefrontal cortex (mPFC) of male mice subjected to chronic social defeat stress (CSDS). The down-regulation of Gm2694 in the mPFC alleviated CSDS-induced depressive-like behaviors through enhanced excitatory synaptic transmission. Furthermore, we found that Gm2694 preferentially interacted with the carboxyl-terminal domain of 78-kilodalton glucose-regulated protein (GRP78), which abrogated GRP78 function and disrupted endoplasmic reticulum homeostasis, resulting in a reduction of the surface expression of AMPA receptors (AMPARs). Overexpression of GRP78 in the mPFC promoted the surface expression of AMPARs and attenuated the CSDS-induced depressive-like behaviors of mice. Together, our results unraveled a previously unknown role of Gm2694 in regulating endoplasmic reticulum homeostasis and excitatory synaptic transmission in depression.

Association between Chinese cooking oil fumes and sleep quality among a middle-aged Chinese population.

Poor sleep quality is an important symptom of many medical or psychiatric disorders. However, the impact of cooking oil fumes (COFs) on sleep quality has not been studied. This population-based cross-sectional study was conducted to examine the association between COFs of Chinese household cooking and sleep quality. Individual sleep quality assessment was completed in 2197 participants with an average age of 37.52 years, through Pittsburgh Sleep Quality Index (PSQI). Information about their cooking practice were also collected by self-reported questionnaire. As an internal biomarker of COFs, urinary 1-hydroxypyrene (1-HOP) (n = 562) was further measured using high-performance liquid chromatography. Binary logistic regression models were performed to evaluate the association between exposure to COFs and individual sleep quality. We found that, subjective poor kitchen ventilation, preheating oil to smoking, and cooking for over 30 minutes were positively associated with overall poor sleep quality (global PSQI score >5) [odds ratio (OR) = 1.75, 95% confidence interval (CI) = 1.43-2.16; 1.25, (1.03-1.52); 1.42, (1.15-1.76), respectively]. After adjusting for potential confounders, subjective poor kitchen ventilation still tend to increase the risk of long sleep latency, sleep disturbances, and daytime dysfunction [OR = 1.37, 95% CI = 1.09-1.73; 1.91, (1.39-2.61); 1.54, (1.23-1.93), respectively]. Similar results were observed in participants who preheated oil to smoking [OR = 1.36, 95% CI = 1.08-1.72; 1.55, (1.14-2.14); 1.25, (1.02-1.55), respectively] and cooked for over 30 minutes [OR = 1.34, 95% CI = 1.05-1.72; 1.46, (1.03-2.06); 1.36, (1.08-1.72), respectively]. Furthermore, high urinary 1-HOP level was also positively associated with overall poor sleep quality (OR = 2.30, 95% CI = 1.31-4.05). The results indicated that exposure to COFs from Chinese household cooking may be a risk factor for poor sleep quality among middle-aged Chinese population.