Neuroscience
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Therapeutic hypothermia with modest results is the only treatment currently available for neonatal hypoxic ischemic encephalopathy (HIE). Endothelin B (ETB) receptors in the brain are shown to have neural restorative capacity. ETB receptors agonist sovateltide alone or as an adjuvant therapy may enhance neurovascular remodeling in HIE. ⋯ Animals receiving sovateltide demonstrated a significant (p < 0.0001) upregulation of ETB receptor, VEGF, and NGF expression in the brain compared to vehicle-treated animals. Additionally, sovateltide alone or in combination with therapeutic hypothermia significantly (p < 0.001) reduced cell death when compared to vehicle or therapeutic hypothermia alone, demonstrating that sovateltide is neuroprotective and attenuates neural damage following HIE. These findings are important and merit additional studies for development of new interventions for improving neurodevelopmental outcomes after HIE.
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The role of normal sensory inputs in the development of sensory cortices is well known, however, their impacts on the hippocampus, an integrator of sensory modalities with important roles in cognitive functions, has received much less attention. Here, we applied a long-term sensory deprivation paradigm by trimming the rats' whiskers bilaterally, from postnatal day 3 to 59. Female sensory-deprived (SD) rats showed more on-wall rearing and visits to the center of the open-field box, shorter periods of grooming, less defecation and less anxiety-like behaviors in the elevated plus-maze compared to controls, who had their intact whiskers brushed. ⋯ Sholl analysis of CA3 neurons in SD animals also disclosed significantly more branched apical dendrites in males and basal dendrites in females. Sensory deprivation also led to a considerable spine loss and variation of different spine types in a sex-dependent manner. Our findings suggest that experience-dependent structural plasticity is capable of spreading far beyond the manipulated sensory zones and the inevitable functional alterations can be expressed in a multifactorial sex-dependent manner.
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Obesity and depression tend to co-occur, and obese patients with chronic low-grade inflammation have a higher risk of developing depression. However, mechanisms explaining these connections have not been fully elucidated. Here, an animal model of comorbid obesity and depression induced by high-fat diet (HFD) combined with chronic unpredictable mild stress (CUMS) was used, and sucrose preference, open field, elevated plus maze and Morris water maze tests were used to detected depression-and anxiety-like behaviors and spatial memory. ⋯ The HFD and CUMS alone and combination of them increased levels of IL-1β, IL-6 and TNF-α in the hippocampus and prefrontal cortex, which was significantly related to depression-like behaviors. Further, NF-κB protein and mRNA levels and microglial activation in the hippocampus and prefrontal cortex significantly increased in stressed, obese and comorbid groups, with animals in comorbid group having the highest NF-κB mRNA levels in the hippocampus and level of NF-κB proteins in the prefrontal cortex, and the highest microglial activation in both brain areas. The study concluded that HFD and CUMS alone and combination induce depression-like symptoms, abnormal serum lipid levels, microglial activation and increased inflammatory cytokines in the brain, effects that are possibly mediated by TLR4-NF-κB signaling.