Molecular neurobiology
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Molecular neurobiology · Oct 2020
Optogenetic Activation of Dopamine Receptor D1 and D2 Neurons in Anterior Cingulate Cortex Differentially Modulates Trigeminal Neuropathic Pain.
Anterior cingulate cortex (ACC) is a critical brain center for chronic pain processing. Dopamine signaling in the brain has been demonstrated to contribute to descending pain modulation. However, the role of ACC dopamine receptors in chronic neuropathic pain remains unclear. ⋯ We observed that dopamine receptors D1 and D2 in the ACC are primarily expressed in excitatory neurons and that the D2 receptor is differentially regulated in the early and late phases of trigeminal neuropathic pain. Optogenetic activation of D1-expressing neurons in the ACC markedly exacerbates CCI-ION-induced trigeminal neuropathic pain in both early and late phases, but optogenetic activation of D2-expressing neurons in the ACC robustly ameliorates such pain in its late phase. Our results suggest that dopamine receptors D1 and D2 in the ACC play different roles in the modulation of trigeminal neuropathic pain.
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Molecular neurobiology · May 2020
ReviewTumor Development and Angiogenesis in Adult Brain Tumor: Glioblastoma.
Angiogenesis is the growth of new capillaries from the preexisting blood vessels. Glioblastoma (GBM) tumors are highly vascularized tumors, and glioma growth depends on the formation of new blood vessels. Angiogenesis is a complex process involving proliferation, migration, and differentiation of vascular endothelial cells (ECs) under the stimulation of specific signals. ⋯ Various angiogenic factors and genes have been identified that stimulate glioma angiogenesis. Therefore, attention has been directed to anti-angiogenesis therapy in which glioma proliferation is inhibited by inhibiting the formation of new tumor vessels using angiogenesis inhibitory factors and drugs. Here, in this review, we highlight and summarize the various molecular mediators that regulate GBM angiogenesis with focus on recent clinical research on the potential of exploiting angiogenic pathways as a strategy in the treatment of GBM patients.
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Molecular neurobiology · May 2020
Comparative StudyComparative Pro-cognitive and Neurochemical Profiles of Glycine Modulatory Site Agonists and Glycine Reuptake Inhibitors in the Rat: Potential Relevance to Cognitive Dysfunction and Its Management.
Frontocortical NMDA receptors are pivotal in regulating cognition and mood, are hypofunctional in schizophrenia, and may contribute to autistic spectrum disorders. Despite extensive interest in agents potentiating activity at the co-agonist glycine modulatory site, few comparative functional studies exist. This study systematically compared the actions of the glycine reuptake inhibitors, sarcosine (40-200 mg/kg) and ORG24598 (0.63-5 mg/kg), the agonists, glycine (40-800 mg/kg), and D-serine (10-160 mg/kg) and the partial agonists, S18841 (2.5 mg/kg s.c.) and D-cycloserine (2.5-40 mg/kg) that all dose-dependently prevented scopolamine disruption of social recognition in adult rats. ⋯ S18841 blocked deficits in NOR following microinjection into the PFC (2.5-10 μg/side) but not the striatum. Finally, in rats socially isolated from weaning (a neurodevelopmental model of schizophrenia), S18841 (2.5 and 10 mg/kg s.c.) reversed impairment of NOR and contextual fear-motivated learning without altering isolation-induced hyperactivity. In conclusion, despite contrasting neurochemical profiles, partial glycine site agonists and glycine reuptake inhibitors exhibit comparable pro-cognitive effects in rats of potential relevance to treatment of schizophrenia and other brain disorders where cognitive performance is impaired.
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Molecular neurobiology · Feb 2020
White Matter Abnormalities Linked to Interferon, Stress Response, and Energy Metabolism Gene Expression Changes in Older HIV-Positive Patients on Antiretroviral Therapy.
Neurocognitive impairment (NCI) remains a significant cause of morbidity in human immunodeficiency virus (HIV)-positive individuals despite highly active antiretroviral therapy (HAART). White matter abnormalities have emerged as a key component of age-related neurodegeneration, and accumulating evidence suggests they play a role in HIV-associated neurocognitive disorders. Viral persistence in the brain induces chronic inflammation associated with lymphocytic infiltration, microglial proliferation, myelin loss, and cerebrovascular lesions. ⋯ Machine learning identified a 15-gene signature predictive of HIV status that was validated in an independent cohort. No specific gene expression patterns were associated with NCI. These findings suggest therapies that decrease chronic inflammation while protecting mitochondrial function may help to preserve white matter integrity in older HIV+ individuals.
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Molecular neurobiology · Jan 2020
Sevoflurane-Induced Dysregulation of Cation-Chloride Cotransporters NKCC1 and KCC2 in Neonatal Mouse Brain.
The cation-chloride cotransporters Na+-K+-2Cl--1 (NKCC1) and K+-2Cl--2 (KCC2) critically regulate neuronal responses to gamma-aminobutyric acid (GABA). NKCC1 renders GABA excitatory in immature neurons while expression of KCC2 signals GABA maturation to its inhibitory role. Imbalances in NKCC1/KCC2 alter GABA neurotransmission, which may contribute to hyperexcitability and blunted inhibition in neurocircuitry after neonatal exposure to anesthesia. ⋯ After propofol challenge on PND8, pups previously exposed to sevoflurane on PND7 regained righting reflex significantly faster than their non-exposed cohort (p < 0.001). Disturbing NKCC1/KCC2 balance may underlie circuit hyperexcitability and contribute to neurodevelopmental impairments we have observed in previous studies of neonatal anesthesia exposure. Human infants previously exposed to anesthesia may require higher concentrations of anesthetic drugs, potentially compounding their susceptibility for neurodevelopmental sequalae.