Neurotransmission in dentate gyrus (DG) is critical for spatial coding, learning memory, and emotion processing. Although DG dysfunction is implicated in psychiatric disorders, including schizophrenia, underlying pathological mechanisms remain unclear. Here we report that transmembrane protein 108 (Tmem108), a novel schizophrenia susceptibility gene, is highly enriched in DG granule neurons and its expression increased at the postnatal period critical for DG development. Tmem108 is specifically expressed in the nervous system and enriched in the postsynaptic density fraction. Tmem108-deficient neurons form fewer and smaller spines, suggesting that Tmem108 is required for spine formation and maturation. In agreement, excitatory postsynaptic currents of DG granule neurons were decreased in Tmem108 mutant mice, indicating a hypofunction of glutamatergic activity. Further cell biological studies indicate that Tmem108 is necessary for surface expression of AMPA receptors. Tmem108-deficient mice display compromised sensorimotor gating and cognitive function. Together, these observations indicate that Tmem108 plays a critical role in regulating spine development and excitatory transmission in DG granule neurons. When Tmem108 is mutated, mice displayed excitatory/inhibitory imbalance and behavioral deficits relevant to schizophrenia, revealing potential pathophysiological mechanisms of schizophrenia.
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http://dx.doi.org/10.1073/pnas.1618213114 | DOI Listing |
PLoS One
January 2025
Department of Clinical Science, SUS, Division of Islet Cell Physiology, University of Lund, Malmö, Sweden.
The impact of islet neuronal nitric oxide synthase (nNOS) on glucose-stimulated insulin secretion (GSIS) is less understood. We investigated this issue by performing simultaneous measurements of the activity of nNOS versus inducible NOS (iNOS) in GSIS using isolated murine islets. Additionally, the significance of extracellular NO on GSIS was studied.
View Article and Find Full Text PDFFront Immunol
January 2025
Institute of Structural Pharmacology and Traditional Chinese Medicine (TCM) Chemical Biology, Fujian Key Laboratory of Chinese Materia Medica, College of Pharmacy, Fujian University of Traditional Chinese Medicine, Fuzhou, China.
Object: Neuroinflammation mediated by microglia has emerged as a critical factor in ischemic stroke and neuronal damage. Gualou Guizhi Granule (GLGZG) has been shown to suppress inflammation in lipopolysaccharide (LPS)-activated microglia, though the underlying mechanisms and its protective effects against neuronal apoptosis remain unclear. This study aims to investigate how GLGZG regulates the Notch signaling pathway in microglia to reduce neuroinflammation and protect neurons from apoptosis.
View Article and Find Full Text PDFJ Neural Transm (Vienna)
January 2025
Institut für Zellbiochemie, OE 4310, Medizinische Hochschule Hannover, 30623, Hannover, Germany.
Botulinum neurotoxins (BoNT) are established biopharmaceuticals for neuromuscular and secretory conditions based on their ability to block neurotransmitter release from neurons by proteolyzing specific soluble N-ethylmaleimide-sensitive factor attachment protein receptor (SNARE) proteins. Recently, a mutant catalytic domain of serotype E (LC/E) exhibiting 16 mutations was reported to cleave the phosphatase and tensin homolog (PTEN). This molecule represents an attractive new target in neurons as several reports support PTEN knockdown as a strategy to stimulate axonal regeneration after injury.
View Article and Find Full Text PDFJ Ethnopharmacol
January 2025
Department of Pharmacology, Shenyang Pharmaceutical University, Shenyang, Liaoning, China; College of Pharmacy, Shenzhen Technology University, Shenzhen, Guangdong, China. Electronic address:
Ethnopharmacological Relevance: Shilong Qingxue Granule (SQG), a traditional Chinese medicine, effectively treats the secondary neurological damage and functional deficits caused by cerebral hemorrhage, though its exact mechanism remains unclear.
Aim Of The Study: This study aimed to investigate the effects of SQG and its mechanisms.
Materials And Methods: we evaluated the effects of SQG and its extracts on glutamate induced nerve damage using in vivo and in vitro models.
J Neurosci
January 2025
Department of Cellular and Molecular Medicine, University of Ottawa, Ottawa, ON, Canada, K1N 6N5
GABAergic neurons in basal forebrain (BF) nuclei project densely to all layers of the mouse main olfactory bulb (OB), the first relay in odor information processing. However, BF projection neurons are diverse and the contribution of each subtype to odor information processing is not known. In the present study, we used retrograde and anterograde tracing methods together with whole-brain light-sheet analyses, patch-clamp recordings coupled with optogenetic and chemogenetic approaches during spontaneous odor discrimination, and go/no-go odor discrimination/learning tests to characterize the synaptic targets in the OB of BF calretinin-expressing (CR+) GABAergic cells and to reveal their functional implications.
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