Delayed therapeutic responses and limited efficacy are the main challenges of existing antidepressant drugs, thereby incentivizing the search for new potential treatments. Cannabidiol (CBD), non-psychotomimetic component of cannabis, has shown promising antidepressant effects in different rodent models, but its mechanism of action remains unclear. Herein, we investigated the antidepressant-like effects of repeated CBD treatment on behavior, neuroplasticity markers and lipidomic profile in the prefrontal cortex (PFC) of Flinders Sensitive Line (FSL), a genetic animal model of depression, and their control counterparts Flinders Resistant Line (FRL) rats. Male FSL animals were treated with CBD (10 mg/kg; i.p.) or vehicle (7 days) followed by Open Field Test (OFT) and the Forced Swimming Test (FST). The PFC was analyzed by a) western blotting to assess markers of synaptic plasticity and cannabinoid signaling in synaptosome and cytosolic fractions; b) mass spectrometry-based lipidomics to investigate endocannabinoid levels (eCB). CBD attenuated the increased immobility observed in FSL, compared to FRL in FST, without changing the locomotor behavior in the OFT. In synaptosomes, CBD increased ERK1, mGluR5, and Synaptophysin, but failed to reverse the reduced CB1 and CB2 levels in FSL rats. In the cytosolic fraction, CBD increased ERK2 and decreased mGluR5 expression in FSL rats. Surprisingly, there were no significant changes in eCB levels in response to CBD treatment. These findings suggest that CBD effects in FSL animals are associated with changes in synaptic plasticity markers involving mGluR5, ERK1, ERK2, and synaptophysin signaling in the PFC, without increasing the levels of endocannabinoids in this brain region.
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http://dx.doi.org/10.1016/j.neuropharm.2024.109870 | DOI Listing |
Nat Commun
January 2025
Department of Medical Biochemistry and Biophysics, Karolinska Institutet, Stockholm, Sweden.
Identifying cell types and brain regions critical for psychiatric disorders and brain traits is essential for targeted neurobiological research. By integrating genomic insights from genome-wide association studies with a comprehensive single-cell transcriptomic atlas of the adult human brain, we prioritized specific neuronal clusters significantly enriched for the SNP-heritabilities for schizophrenia, bipolar disorder, and major depressive disorder along with intelligence, education, and neuroticism. Extrapolation of cell-type results to brain regions reveals the whole-brain impact of schizophrenia genetic risk, with subregions in the hippocampus and amygdala exhibiting the most significant enrichment of SNP-heritability.
View Article and Find Full Text PDFBMC Geriatr
January 2025
Department of Rehabilitation Medicine (Rehabilitation Center), Qilu Hospital of Shandong University, No. 107, Wenhuaxi Road, Jinan , Shandong, 250012, China.
Background: Mild cognitive impairment (MCI) is a high-risk factor for dementia and dysphagia; therefore, early intervention is vital. The effectiveness of intermittent theta burst stimulation (iTBS) targeting the right dorsal lateral prefrontal cortex (rDLPFC) remains unclear.
Methods: Thirty-six participants with MCI were randomly allocated to receive real (n = 18) or sham (n = 18) iTBS.
Prog Neurobiol
January 2025
Section on Cognitive Neurophysiology and Imaging, National Institute of Mental Health; Bethesda, MD, USA; Neurophysiology Imaging Facility, National Institute of Mental Health, National Institute of Neurological Disorders and Stroke, National Eye Institute; Bethesda, MD, USA. Electronic address:
The macaque cerebral cortex contains concentrations of neurons that prefer faces over inanimate objects. Although these so-called face patches are thought to be specialized for the analysis of facial signals, their exact tuning properties remain unclear. For example, what happens when an object by chance resembles a face? Everyday objects can sometimes, through the accidental positioning of their internal components, appear as faces.
View Article and Find Full Text PDFBiomed J
January 2025
Department of Anesthesiology, Perioperative and Pain Medicine, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, Henan Province 450000, China; Henan Province International Joint Laboratory of Pain, Cognition and Emotion, Zhengzhou, Henan Province 450000, China. Electronic address:
Sleep is crucial for sustaining normal physiological functions, and sleep deprivation has been associated with increased pain sensitivity. The histone deacetylases (HDACs) are known to significantly regulate in regulating neuropathic pain, but their involvement in nociceptive hypersensitivity during sleep deprivation is still not fully understood. Utilizing a modified multi-platform water environment technique to establish a sleep deprivation model.
View Article and Find Full Text PDFMetab Brain Dis
January 2025
Department of Biomedical and Biotechnological Sciences, Human Anatomy and Histology Section, School of Medicine, University of Catania, Catania, Italy.
SERPINA3, a serine protease inhibitor, is strongly associated with neuroinflammation, a typical condition of AD. Its expression is linked to microglial and astrocytic markers, suggesting it plays a significant role in modulating neuroinflammatory responses. In this study, we examined the SERPINA3 expression levels, along with CHI3L1, in various brain regions of AD patients and non-demented healthy controls (NDHC).
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