The beneficial pharmacological effects of Uncaria rhynchophylla in neurodegenerative diseases: focus on alkaloids.

With the intensification of aging population, the prevention or treatment of neurodegenerative diseases, such as Parkinson's disease and Alzheimer's disease, has drawn more and more attention. As a long used traditional Chinese medicine, Uncaria rhynchophylla (Miq.) Jacks., named Gouteng in Chinese, has been reported to have an effective neuroprotective role in neurodegenerative diseases. In this review, the beneficial pharmacological effects and signaling pathways of herbal formulas containing U. rhynchophylla, especially major compounds identified from U. rhynchophylla, such as corynoxine B, corynoxine, rhynchophylline, and isorhynchophylline, in neurodegenerative diseases, were summarized, which not only provide an overview of U. rhynchophylla for the prevention or treatment of neurodegenerative diseases but also give some perspective to the development of new drugs from traditional Chinese medicine.

Unconscious Integration of Categorical Relationship of Two Subliminal Numbers in Comparison with "5".

Many studies have shown that the brain can process subliminal numerals, i.e., participants can categorize a subliminal number into two categories: greater than 5 or less than 5. In the context of many studies on the unconscious integration of multiple subliminal stimuli, the issue of whether multiple subliminal numbers can be integrated is contentious. The same-different task is regarded as a perfect tool to explore unconscious integration. In the two experiments reported, we used a same-different task in which a pair of masked prime numbers was followed by a pair of target numbers, and participants were asked to decide whether the two target numbers were on the same (both smaller or larger than 5) or different sides (one smaller, the other larger than 5) of 5 in magnitude. The results indicated that the prime numbers could be categorized unconsciously, which was reflected by the category priming effect, and that the unconscious category relationship of the two prime numbers could affect the judgment on the category relationship of the two target numbers, as reflected by the response priming effect. The duration of the prime-to-target interstimulus interval (ISI) was also manipulated, showing a positive compatibility effect (PCE) of category priming and a negative compatibility effect (NCE) of response priming no matter whether the ISI was short (50 ms) or long (150 ms). The NCE, which occurred when the prime-to-target ISI was relatively short in this study, contradicted the conventional view but was consistent with previous results of unconscious integration based on an attention modulation mechanism. Importantly, this study provided evidence for the still-under-debate issue of numerical information integration.

GABAergic synapses from the ventral lateral septum to the paraventricular nucleus of hypothalamus modulate anxiety.

Emotional disorders, such as anxiety and depression, represent a major societal problem; however, the underlying neurological mechanism remains unknown. The ventral lateral septum (LSv) is implicated in regulating processes related to mood and motivation. In this study, we found that LSv GABAergic neurons were significantly activated in mice experiencing chronic social defeat stress (CSDS) after exposure to a social stressor. We then controlled LSv GABAergic neuron activity using a chemogenetic approach. The results showed that although manipulation of LSv GABAergic neurons had little effect on anxiety-like behavioral performances, the activation of LSv GABAergic neurons during CSDS worsened social anxiety during a social interaction (SI) test. Moreover, LSv GABAergic neurons showed strong projections to the paraventricular nucleus (PVN) of the hypothalamus, which is a central hub for stress reactions. Remarkably, while activation of GABAergic LSv-PVN projections induced social anxiety under basal conditions, activation of this pathway during CSDS alleviated social anxiety during the SI test. On the other hand, the chemogenetic manipulation of LSv GABAergic neurons or LSvGABA-PVN projections had no significant effect on despair-like behavioral performance in the tail suspension test. Overall, LS GABAergic neurons, particularly the LSv GABAergic-PVN circuit, has a regulatory role in pathological anxiety and is thus a potential therapeutic target for the treatment of emotional disorders.

5-HT1A receptors within the intermediate lateral septum modulate stress vulnerability in male mice.

Chronic stress is a major risk factor for psychiatric disorders. However, certain individuals may be at higher risk due to greater stress susceptibility. Elucidating the neurobiology of stress resilience and susceptibility may facilitate the development of novel strategies to prevent and treat stress-related disorders such as depression. Mounting evidence suggests that the serotonin (5-HT) system is a major regulator of stress sensitivity. In this study, we assessed the functions of 5-HT1A and 5-HT2A receptors within the lateral septum (LS) in regulating stress vulnerability. Among a group of male mice exposed to chronic social defeat stress (CSDS), 47.2% were classified as stress-susceptible, and these mice employed more passive coping strategies during the defeat and exhibited more severe anxiety- and depression-like behaviors during the following behavioral tests. These stress-susceptible mice also exhibited elevated neuronal activity in the LS as evidenced by greater c-Fos expression, greater activity of 5-HT neurons in both the dorsal and median raphe nucleus, and downregulated expression of the 5-HT1A receptor in the intermediate LS (LSi). Finally, we found the stress-induced social withdrawal symptoms could be rapidly relieved by LSi administration of 8-OH-DPAT, a 5-HT1A receptor agonist. These results indicate that 5-HT1A receptors within the LSi play an important role in stress vulnerability in mice. Therefore, modulation of stress vulnerable via 5-HT1A receptor activation in the LSi is a potential strategy to treat stress-related psychiatric disorders.