Transient receptor potential (TRP) channels are critical receptors in the transduction of nociceptive stimuli. The microenvironment of diverse types of cancer releases substances, including growth factors, neurotransmitters, and inflammatory mediators, which modulate the activity of TRPs through the regulation of intracellular signaling pathways. The modulation of TRP channels is associated with the peripheral sensitization observed in patients with cancer, which results in mild noxious sensory stimuli being perceived as hyperalgesia and allodynia. Secondary metabolites derived from plant extracts can induce the activation, blocking, and desensitization of TRP channels. Thus, these compounds could act as potential therapeutic agents, as their antinociceptive properties could be beneficial in relieving cancer-derived pain. In this review, we will summarize the role of TRPV1 and TRPA1 in pain associated with cancer and discuss molecules that have been reported to modulate these channels, focusing particularly on the mechanisms of channel activation associated with molecules released in the tumor microenvironment.

Gap junction (GJ) channels and their connexins (Cxs) are complex proteins that have essential functions in cell communication processes in the central nervous system (CNS). Neurons, astrocytes, oligodendrocytes, and microglial cells express an extraordinary repertory of Cxs that are important for cell to cell communication and diffusion of metabolites, ions, neurotransmitters, and gliotransmitters. GJs and Cxs not only contribute to the normal function of the CNS but also the pathological progress of several diseases, such as cancer and neurodegenerative diseases. Besides, they have important roles in mediating neuroprotection by internal or external molecules. However, regulation of Cx expression by epigenetic mechanisms has not been fully elucidated. In this review, we provide an overview of the known mechanisms that regulate the expression of the most abundant Cxs in the central nervous system, Cx30, Cx36, and Cx43, and their role in brain cancer, CNS disorders, and neuroprotection. Initially, we focus on describing the Cx gene structure and how this is regulated by epigenetic mechanisms. Then, the posttranslational modifications that mediate the activity and stability of Cxs are reviewed. Finally, the role of GJs and Cxs in glioblastoma, Alzheimer’s, Parkinson’s, and Huntington’s diseases, and neuroprotection are analyzed with the aim of shedding light in the possibility of using Cx regulators as potential therapeutic molecules.

A reduced dendritic complexity, especially in regions such as the hippocampus and the prefrontal cortex, has been linked to the pathophysiology of some neuropsychiatric disorders, in which synaptic plasticity and functions such as emotional and cognitive processing are compromised. For this reason, the identification of new therapeutic strategies would be enriched by the search for metabolites that promote structural plasticity. The present study evaluated the dendritogenic potential of the ethanol extract of Lippia alba, an aromatic plant rich in flavonoids and terpenes, which has been widely used in traditional medicine for its presumed analgesic, anxiolytic, and antidepressant potential. An in vitro model of rat cortical neurons was used to determine the kinetics of the plant’s effect at different time intervals. Changes in morphological parameters of the neurons were determined, as well as the dendritic complexity, by Sholl analysis. The extract promotes the outgrowth of dendritic branching in a rapid and sustained fashion, without being cytotoxic to the cells. We found that this effect could be mediated by the phosphatidylinositol 3-kinase pathway, which is involved in mechanisms of neuronal plasticity, differentiation, and survival. The evidence presented in this study provides a basis for further research that, through in vivo models, can delve into the plant’s therapeutic potential.

Astrocytes, the most abundant cell in the Central Nervous System (CNS), modulate synaptic activity and provide metabolic and trophic support to neurons. It has been shown that during chronic pain and neurodegenerative diseases astrocytes produce a set of molecules that can be beneficial or detrimental to neurons. In addition, astrocytes have changes in the expression and activity of different proteins like enzymes and membrane proteins that modulate their response during these diseases. A common therapeutic approach to the treatment of some CNS diseases, is the use of electrical neuromodulation (ENM) of the brain areas involved in the disease. Although the complete mechanisms have not fully understood, ENM can work by resetting the neuron´s electrical properties, which induces changes in the oscillatory circuits involved in the genesis of the disease. However, less is known about how EMN can affect other cells of the CNS as astrocytes. This workshop will initially discuss the most relevant aspects of ENM clinical use for later focus in the cellular and molecular mechanisms by which ENM can regulate astrocytes physiology and the impact of this regulation in the function and survival of neurons in different CNS pathologies in which EMN has shown successful results. • Present and future of electrical neuromodulation of the Central Nervous System Guillermo Alfonso Monsalve Duarte. • Role of ion channel in astrocytes in the normal and pathologic brain Yolima P Torres • Electrical neuromodulation of astrocytes as a regulator of inflammation in the Central Nervous System Jhon J Sutachan • Metabolic implication of electrical neuromodulation in the metabolism of astrocytes Sonia Luz Albarracín

Neuroplasticity refers to the nervous system’s ability to modify its structure and function in response to intrinsic and extrinsic stimuli. Impairments in this capacity are associated with various neurological disorders, underscoring the need for therapies that preserve or enhance neuronal plasticity. Medicinal plants offer a promising source of bioactive compounds with neuroplastic properties and neuroprotective potential. In this work, we report the chemical and neuroplastic properties of Tillandsia usneoides, a medicinal native plant from America. Ethanolic extracts (EtOH) of leaves and stems, along with subfractionated ethyl acetate (EtOAc) and hydroethanolic (H₂O:EtOH) extracts, were analyzed using High-Performance Thin-Layer Chromatography (HPTLC) and Ultra-Performance Liquid Chromatography coupled with a Diode Array Detector (UPLC-DAD), revealing the presence of 14 phenolic acids, 6 flavonoids, and triterpene. Additionally, functional analysis using Sholl analysis showed that the EtOAc fraction of Tillandsia usneoides significantly enhanced structural plasticity in vitro, increasing both dendritic branching and dendrite length at concentrations between 0.03 and 1 μg mL⁻¹, likely through the activation PI3K/Akt and ERK1/2 signaling pathways. Together, our results suggest that Tillandsia usneoides contains bioactive polar metabolites capable of inducing neuronal structural plasticity.