Neuroscience
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Autism Spectrum Disorders (ASD) and schizophrenia are distinct neurodevelopmental disorders that share certain symptoms and genetic components. Both disorders show abnormalities in dendritic spines, which are the main sites of excitatory synaptic inputs. Recent studies have identified the synaptic scaffolding protein Shank3 as a leading candidate gene for both disorders. ⋯ We identified shared and distinct phenotypes in dendritic spine morphogenesis and plasticity in the ASD-associated InsG3680 mutant mice and the schizophrenia-associated R1117X mutant mice. No significant changes in dendritic arborization were observed in either mutant, raising the possibility that synaptic dysregulation may be a key contributor to the behavioral defects previously reported in these mice. These findings shed light on how patient-linked mutations in SHANK3 affect dendritic spine dynamics in the developing brain, which provides insight into the synaptic basis for the distinct phenotypes observed in ASD and schizophrenia.
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Alzheimer's disease (AD) is a serious neurodegenerative disease characterized by amyloid-β (Aβ) aggregation and neuroinflammation. G-protein-coupled receptor 34 (Gpr34) was found highly expressed in the hippocampus of APP/PS1 mice. However, its role in AD remains unclear. ⋯ On the other hand, the in vivo study showed that Gpr34 knockdown ameliorated the cognitive impairment in APP/PS1 mice, decreased the levels of TNF-α, IL-1β and IL-6, the activation of microglia and ERK/NF-κB signal. In conclusion, Gpr34 knockdown relieved cognitive deficits in APP/PS1 mice and suppressed neuroinflammation and microglial activation, maybe via the ERK/NF-κB signal. It is indicated that the high level of Grp34 in hippocampus may contribute to the pathogenesis of AD.
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Proteinase-activated receptor-1 (PAR1) is expressed in astrocytes of various brain regions, and its activation is involved in the modulation of neuronal activity. Here, we report effects of PAR1 selective agonist TFLLR on respiratory rhythm generation in brainstem-spinal cord preparations. Preparations were isolated from newborn rats (P0-P4) under deep isoflurane anesthesia and were transversely cut at the rostral medulla. ⋯ In conclusion, activation of astrocytes via PAR1 resulted in a decrease of inspiratory C4 burst rate in association with transient hyperpolarization of respiratory-related neurons. After washout, slow and weak excitatory responses appeared. Adenosine may be partially involved in the inhibitory effect of PAR1 activation.
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There is a growing interest for studying the impact of chronic inflammation, particularly lung inflammation, on the brain and behavior. This includes asthma, a chronic inflammatory condition, that has been associated with psychiatric conditions such as posttraumatic stress disorder (PTSD). Although asthma is driven by elevated production of Th2 cytokines (IL-4, IL-5 and IL-13), which drive asthma symptomology, recent work demonstrates that concomitant Th1 or Th17 cytokine production can worsen asthma severity. ⋯ While HDM evoked a Th2-skewed immune response in lung tissue, no significant alterations in brain Th cell subsets were observed. Significantly reduced ΔFosB+ cells in the basolateral amygdala of HDM mice were observed post extinction. Our data indicate that allergen-driven Th2-skewed responses may induce fear extinction promoting effects, highlighting beneficial interactions of Th2-associated immune mediators with fear regulatory circuits.
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The glymphatic system is important for waste removal in the central nervous system. It removes soluble proteins and metabolic waste under the action of aquaporin-4 (AQP4) at the end of astrocytes. The glymphatic system plays a role in numerous neurological diseases; however, the relationship between migraine and the glymphatic system remains unclear. ⋯ Then, further suppression of glymphatic function by TGN-020 (an AQP4 blocker) aggravated the migraine pathological changes in mice. The results indicated that glymphatic dysfunction may aggravate migraine pathology. Therefore, our findings revealed the potential role of the glymphatic system in migraine, providing possible targets for migraine prevention and treatment.