Neuroscience
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Focal administration of pharmacological agents during in vivo recordings is a useful technique to study the functional properties of neural microcircuits. However, the lack of visual control makes this task difficult and inaccurate, especially when targeting small and deep regions where spillover to neighboring regions is likely to occur. An additional problem with recording stability arises when combining focal drug administration with in vivo intracellular recordings, which are highly sensitive to mechanical vibrations. ⋯ We applied tetrodotoxin (TTX 10 µM) during whole-cell recordings in the striatum, while simultaneously obtaining extracellular recordings in S1 and M1. The focal application of TTX in the striatum blocked Up states in the recorded striatal neurons, without affecting the cortical activity. We also describe two different approaches for precisely releasing the drugs without unwanted leakage along the pipette approach trajectory.
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Inflammation in the hypothalamic paraventricular nucleus (PVN) contributes to neurohumoral excitation and its adverse consequences in systolic heart failure (HF). The stimuli that trigger inflammation in the PVN in HF are not well understood. Angiotensin II (AngII) has pro-inflammatory effects, and circulating levels of AngII increase in HF. ⋯ The central abnormalities were ameliorated in HF rats that received AT1aR shRNA, as were plasma norepinephrine and vasopressin. Sham rats that received AT1aR shRNA had reduced SFO AT1aR mRNA but no other changes compared with Sham rats that received scrambled shRNA. The results suggest that activation of AT1aR in the SFO upregulates the neuroinflammation in the PVN that contributes to neurohumoral excitation in HF.
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Increasing evidence has shown that prenatal stress (PS) could cause depression-like behavior in the offspring, which is sex-specific. However, the underlying mechanisms remain to be elucidated. This study is to investigate the involvement of tryptophan hydroxylase 2 (Tph2) H3K9 acetylation (H3K9ac) modification on PS-induced depression-like behavior in juvenile offspring rats (JOR). ⋯ However, no significant effects were observed for the female juvenile offspring rats (FJORs). In conclusion, our results showed that the Tph2 H3K9ac modification is only involved in PS-induced depression-like behavior in MJOR, in a sex-specific manner. These findings might contribute to the understanding of the disease pathogenesis and clinical treatment in future.
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Amyotrophic lateral sclerosis (ALS) is a chronic, fatal neurodegenerative disorder characterized by the progressive loss of upper and lower motor neurons. Currently, there is no effective drug for ALS. Recent studies in ALS model mice have shown that insulin-like growth factor-1 (IGF1) may be a promising therapeutic drug. ⋯ Furthermore, the results were supported by experiments in which the CRISPR/Cas9 system was used to knock-down IGF1 in ALS mice (mIGF1). Our data indicate that IGF1-mediated suppression of NF-κB activation in microglia is a novel molecular mechanism underlying MN death in ALS. It provides new insight into IGF1 and points toward novel therapeutic targets of IGF1 in ALS.