VGLUT2 may improve cognitive function in depressed rats by protecting prefrontal cortex neurons.

Objective: Depression may be accompanied by cognitive impairment, but its pathogenesis remains unclear. This study aims to investigate the protective effects of fluoxetine on behavioral performance and prefrontal cortex neuronal damage in rats with depression-associated cognitive impairment, based on the observation of VGLUT2 protein expression. Methods: Forty-five SPF-grade male SD rats were randomly divided into three groups (n = 15): normal control group (CON), depression group (DD), and fluoxetine group (DD + F). The CON group was reared normally, while the DD and DD + F groups underwent chronic unpredictable mild stress (CUMS) combined with social isolation to induce a depression-related cognitive dysfunction model. After modeling, the DD + F group was treated with fluoxetine (10 mg/kg, ig) for 14 days. Behavioral tests were performed to assess changes in mood, cognition, learning, and social abilities. Histopathological observations were made to examine pathological changes, neuronal apoptosis, ultrastructure, and dendritic spine density in the prefrontal cortex. The concentration, relative expression level, and mRNA expression of VGLUT2 protein were also measured. Finally, a correlation analysis was performed between the relative expression level and mRNA expression of VGLUT2 protein and the pathological changes in neurons. Results: Compared to the CON group, the DD group exhibited decreased body weight, anhedonia, increased behavioral despair, reduced locomotor activity and spontaneous exploratory behavior, impaired spatial learning and memory, and decreased social interaction and social cognitive ability. Pathological damage was observed in the prefrontal cortex, with neuronal apoptosis, ultrastructural damage, and reduced neuroplasticity. The concentration, relative expression, and mRNA expression levels of VGLUT2 protein were decreased. Following fluoxetine intervention, the above behavioral phenotypes improved; pathological damage showed varying degrees of recovery; and the concentration, relative expression, and mRNA expression levels of VGLUT2 protein increased. Finally, there was a significant correlation between VGLUT2 protein expression and pathological changes in the prefrontal cortex. Conclusion: After 28 days of CUMS combined with isolation rearing, rats exhibited impairments in mood, cognition, learning, and social abilities, with neuronal damage and decreased VGLUT2 protein levels in the prefrontal cortex. Following fluoxetine intervention, VGLUT2 protein expression increased, neuronal repair in the prefrontal cortex occurred, depressive-like behavior improved, and cognitive learning and social abilities were restored.

Robust CRISPR/Mb2Cas12a genome editing tools in cotton plants.

The efficiency and accuracy of the CRISPR/Mb2Cas12a system were demonstrated in cotton, achieving an efficiency of over 90% at target sites. Notably, Mb2Cas12a exhibited significant tolerance under different temperatures ranging from 22°C to 32°C. Additionally, the Mb2Cas12a system revealed effective editing at more relaxed VTTV PAM sites in the cotton genome, which expanded the genome editing range by approximately 2.6-fold than the wide-type LbCas12a. Finally, a multiplex genome editing system was also developed based on Mb2Cas12a, enabling simultaneous editing of eight target sites using a single crRNA cassette.

Analysis of functional connectivity changes in attention networks and default mode networks in patients with depression and insomnia.

PURPOSE: Major Depressive Disorder (MDD) and Insomnia Disorder (ID) are prevalent psychiatric conditions often occurring concurrently, leading to substantial impairment in daily functioning. Understanding the neurobiological underpinnings of these disorders and their comorbidity is crucial for developing effective interventions. This study aims to analyze changes in functional connectivity within attention networks and default mode networks in patients with depression and insomnia. METHODS: The functional connectivity alterations in individuals with MDD, ID, comorbid MDD and insomnia (iMDD), and healthy controls (HC) were assessed from a cohort of 174 participants. They underwent rs-fMRI scans, demographic assessments, and scale evaluations for depression and sleep quality. Functional connectivity analysis was conducted using region-of-interest (ROI) and whole-brain methods. RESULTS: The MDD and iMDD groups exhibited higher Hamilton Depression Scale (HAMD) scores compared to HC and ID groups (P < 0.001). Both ID and MDD groups displayed enhanced connectivity between the left and right orbital frontal cortex compared to HC (P < 0.05), while the iMDD group showed reduced connectivity compared to HC and ID groups (P < 0.05). In the left insula, reduced connectivity with the right medial superior frontal gyrus was observed across patient groups compared to HC (P < 0.05), with the iMDD group showing increased connectivity compared to MDD (P < 0.05). Moreover, alterations in functional connectivity between the left thalamus and left temporal pole were found in iMDD compared to HC and MDD (P < 0.05). Correlation analyses revealed associations between abnormal connectivity and symptom severity in MDD and ID groups. CONCLUSIONS: Our findings demonstrate distinct patterns of altered functional connectivity in individuals with MDD, ID, and iMDD compared to healthy controls. These findings contribute to a better understanding of the pathophysiology of depression and insomnia, which could be used as a reference for the diagnosis and treatments of these patients.

Insomniacs show greater prefrontal activation during verbal fluency task compared to non-insomniacs: a functional near-infrared spectroscopy investigation of depression in patients.

BACKGROUND: Previous studies have shown that insomnia affects human prefrontal function and that there are specific patterns of brain activation to counteract sleep and improve cognition. However, the effects of insomnia on the prefrontal cortex of MDD (major depressive disorder) patients and the patterns of activation to counteract sleep in MDD patients remain unclear. The aim of this study is to examine this using fNIRS (functional near-infrared spectroscopy). METHODS: Eighty depressed patients and 44 healthy controls were recruited for this study. fNIRS was used to assess changes in the concentration of oxygenated hemoglobin ([oxy-Hb]) in the prefrontal cortex of all participants during the VFT (verbal fluency test) and to record the number of words created to assess cognitive ability. The Pittsburgh Sleep Quality Index was used to assess sleep quality, and the Hamilton Rating Scale for Depression (24-item) and Hamilton Rating Scale for Anxiety (14-item) were used to assess the severity of depression and anxiety. RESULTS: When comparing patients, the healthy control group had significantly higher [oxy-Hb] values in the bilateral prefrontal cortex during VFT than the MDD group. In the MDD group, the [oxy-Hb] values in all brain regions except the right DLPFC were significantly higher in the group with insomnia than in the group without insomnia, but their VFT performance was significantly lower than in the group without insomnia and the healthy group. PSQI scores were positively correlated with [oxy-Hb] values in some left-brain regions, whereas HAMD and HAMA scores were not correlated with [oxy-Hb] values. CONCLUSION: The PFC was significantly less active during VFT in those with MDD than in healthy controls. All brain regions, except the right DLPFC, were significantly more active in MDD patients with insomnia than in those without insomnia, suggesting that sleep quality needs to be an important indicator in fNIRS screening. In addition, there was a positive correlation between the severity of insomnia in the left VLPFC and the level of activation, suggesting a role for the left brain region in the neurophysiology of overcoming sleepiness in MDD patients. these findings may provide new ideas for the treatment of MDD patients in the future. TRIAL REGISTRATION: Our experiment was registered in the China Clinical Trial Registry (registration number ChiCTR2200065622) on November 10.( The first patient was recruited in 10/11/2022.).

Abnormalities of the Default Mode Network Functional Connectivity in Patients with Insomnia Disorder.

Objective: This paper aimed to probe changes in the default mode network (DMN) functional connectivity (DMNFC) of the brain of patients with insomnia disorder (ID) under the resting state. Methods: A total of 67 patients with ID and 67 graphically matched healthy controls were selected. Then, their general information was collected, followed by a psychological scale valuation. Resting state functional magnetic resonance imaging (rs-fMRI) scanning was conducted. Subsequently, collected statistics were processed, bilateral precuneus and medial superior frontal gyrus were defined as regions of interest (ROI), and the difference in intensity between these two groups was compared. Results: Compared with the healthy control group, the patients in the ID group were observed with abnormalities of DMNFC. Specifically, a significant increase in the functional connectivity (FC) could be observed between the left medial superior frontal gyrus and left central anterior gyrus, the left medial superior frontal gyrus and anterior cingulate gyrus, the right medial superior frontal gyrus and left central anterior gyrus, the left anterior cuneiform and left central anterior/posterior gyrus, the left anterior cuneiform and left superior occipital gyrus, as well as the right anterior cuneiform and left central posterior gyrus. However, the FC between the left anterior cuneiform and the right middle frontal gyrus was weakened, as well as between the left anterior cuneiform and the right angle gyrus and between the right precuneus and the left inferior temporal gyrus. Conclusion: ID patients may suffer changes in FC. The decline of FC in DMN may be one of the underlying causes of ID; the enhancement of FC between DMN and the visual-spatial attention network may play a key role in the mechanisms of impaired brain functional networks of ID.