Major depressive disorder (MDD) is a complex and devastating illness that affects people of all ages. Despite the large use of antidepressants in current medical practice, neither their mechanisms of action nor the aetiology of MDD are completely understood. Experimental evidence supports the involvement of Parvalbumin-positive GABAergic neurons (PV-neurons) in the pathogenesis of MDD. and () encode two homeodomain transcription factors involved in cortical GABAergic differentiation and function. In the mouse, the level of expression of these genes is correlated with the cortical density of PV-neurons and with anxiety-like behaviours. The same genomic region generates the lncRNA which, in humans, participates in the GABAergic regulatory module downregulated in schizophrenia and ASD. Here, we show that the expression levels of in the adult mouse brain are correlated with the immobility time in the forced swim test, which is used to measure depressive-like behaviours. We show that the administration of the antidepressant fluoxetine (Flx) to normal mice induces, within 24 h, a rapid and stable reduction in , and expression in the cerebral cortex through the activation of the TrkB-CREB pathway. Experimental overexpression counteracts the antidepressant effects induced by Flx treatment. Our findings show that one of the short-term effects of Flx administration is the reduction in expression in GABAergic neurons, which, in turn, has direct consequences on expression and on behavioural profiles. Variants in the regulatory network could be implicated in the predisposition to depression and in the variability of patients' response to antidepressant treatment.
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http://dx.doi.org/10.3390/cells13151262 | DOI Listing |
Commun Biol
January 2025
Key Laboratory of Biomedical Engineering of Hainan Province, School of Biomedical Engineering, Hainan University, Sanya, China.
The retrosplenial cortex (RSP) is a complex brain region with multiple interconnected subregions that plays crucial roles in various cognitive functions, including memory, spatial navigation, and emotion. Understanding the afferent and efferent connectivity of the RSP is essential for comprehending the underlying mechanisms of its functions. Here, via viral tracing and fluorescence micro-optical sectioning tomography (fMOST), we systematically investigated the anatomical organisation of the upstream and downstream circuits of glutamatergic and GABAergic neurons in the dorsal and ventral RSP.
View Article and Find Full Text PDFEur J Neurosci
January 2025
Department of Pharmacology, University of Oxford, Oxford, UK.
Cannabinoid receptor 1 (CB1) regulates synaptic transmission through presynaptic receptors in nerve terminals, and its physiological roles are of clinical relevance. The cellular sources and synaptic targets of CB1-expressing terminals in the human cerebral cortex are undefined. We demonstrate a variable laminar pattern of CB1-immunoreactive axons and electron microscopically show that CB1-positive GABAergic terminals make type-2 synapses innervating dendritic shafts (69%), dendritic spines (20%) and somata (11%) in neocortical layers 2-3.
View Article and Find Full Text PDFJ Neuroinflammation
January 2025
Department of Molecular and Integrative Physiology, University of Michigan Medical School, Ann Arbor, MI, USA.
The thrombolytic protease tissue plasminogen activator (tPA) is expressed in the CNS, where it regulates diverse functions including neuronal plasticity, neuroinflammation, and blood-brain-barrier integrity. However, its role in different brain regions such as the substantia nigra (SN) is largely unexplored. In this study, we characterize tPA expression, activity, and localization in the SN using a combination of retrograde tracing and β-galactosidase tPA reporter mice.
View Article and Find Full Text PDFJ Neurosci
January 2025
Laboratory of Cerebral Cortex Research, HUN-REN Institute of Experimental Medicine, Budapest, Hungary
The human hippocampus, essential for learning and memory, is implicated in numerous neurological and psychiatric disorders, each linked to specific neuronal subpopulations. Advancing our understanding of hippocampal function requires computational models grounded in precise quantitative neuronal data. While extensive data exist on the neuronal composition and synaptic architecture of the rodent hippocampus, analogous quantitative data for the human hippocampus remain very limited.
View Article and Find Full Text PDFeNeuro
January 2025
Medical Discovery Team on Addiction, University of Minnesota, Minneapolis, MN.
Food intake is controlled by multiple converging signals: hormonal signals that provide information about energy homeostasis, but also hedonic and motivational aspects of food and food cues that can drive non-homeostatic or "hedonic" feeding. The ventral pallidum (VP) is a brain region implicated in the hedonic and motivational impact of food and foods cues, as well as consumption of rewards. Disinhibition of VP neurons has been shown to generate intense hyperphagia, or overconsumption.
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