Current Neuropharmacology - Online First

Depression is a severe psychiatric disorder characterized by high prevalence rates, elevated suicide risks, and significant relapse rates. Women, particularly during the perimenopausal period, are more vulnerable to developing depression. Fluctuations in estrogen levels during perimenopause can heighten a woman's sensitivity to psychosocial stress. Clinical trials have demonstrated the short-term antidepressant efficacy of estradiol in perimenopausal women. However, the precise mechanisms through which estrogen influences mood disorders during perimenopause remain unclear. This review summarizes the risk factors associated with perimenopausal depression (PMD), examines current research on estrogen therapy, and explores the potential mechanisms and related pathological processes involved in estrogen's role in treating depression. Understanding how estrogen mitigates depressive symptoms in perimenopausal women may help reduce the morbidity and mortality associated with PMD while also alleviating its socioeconomic burden.

Alzheimer's disease is a neurodegenerative disease that impairs cognitive function. The incidence of Alzheimer's disease increases with the increase in the elderly population. Although the clear pathogenesis of Alzheimer's disease is not yet known, the formation of amyloid plaques and tau fibrils, diminished acetylcholine levels, and increased inflammation can be observed in patients. Alzheimer's disease, whose pathogenesis is not fully demonstrated, cannot be treated radically. Since it has been observed that only pharmacological treatment alone isn’t sufficient, alternative approaches have become essential. Among these approaches, nanocarriers greatly facilitate the transport of drugs since the blood-brain barrier is an important obstacle to the penetration of drugs into the brain. Photosensitizers trigger activation after exposure to near-infrared radiation light of a suitable wavelength or laser light, resulting in the selective destruction of Aβ plaques. Photodynamic therapy and photothermal therapy have been investigated for their potential to inhibit Aβ plaques through photosensitizers. By ThT fluorescence measurements, TAS-loaded Ce6 micelles show inhibiting Aβ monomers from formation Aβ aggregates and degradation of protofibrills to small fragments. By using these photosensitizers, near-infrared radiation fluorescence imaging can be used as a theranostic. In this review, potential treatment options for photodynamic therapy and photothermal therapy for Alzheimer's disease are summarised, and a simultaneous or combined approach is discussed, taking into account potential nanotheranostics.

Epilepsy is a prevalent and severe neurological condition characterized by recurring seizures. It impacts over 70 million individuals worldwide, posing a substantial challenge to public health and placing a heavy burden on society. Glycerophospholipids are an essential component of neuronal cell membranes. Their metabolism is strictly regulated, and maintaining their homeostasis is crucial for the optimal function of the nervous system. Research indicates that disruptions in glycerophospholipid metabolism are commonly detected in patients with epilepsy and animal models. However, the precise molecular mechanisms behind these disruptions remain unclear. Existing evidence indicates that neuroinflammation, oxidative stress, genetic mutations, and ion channel dysfunction are crucial factors contributing to glycerophospholipids imbalance and epilepsy. Further, therapeutic interventions targeting these pathological processes, such as regulating neuroinflammation and oxidative stress or restoring the balance of glycerophospholipid metabolism, may provide new avenues for epilepsy treatment. This review aims to provide an in-depth analysis of the potential mechanisms underlying the relationship between glycerophospholipid metabolism disorders and epilepsy, exploring potential therapeutic targets and diagnostic biomarkers.

The nervous system, including the central nervous system and peripheral nervous system, has the most intricate structure and function among all systems in the human body. In studies of physiological and pathological functions, cell culture systems serve as an indispensable tool to simulate the nervous system in vivo. Two-dimensional (2D), three-dimensional (3D), and four-dimensional (4D) neural cell culture systems are used to assess the functional interconnectivity of neuronal tissues and have markedly advanced in recent years. Although 2D culture systems have predominated, they cannot accurately recapitulate the dynamic complexity of the in vivo environment, cell-cell communication, and nervous system structures. Consequently, studies have shifted to using 3D or 4D cell culture systems to achieve more realistic biochemical and biomechanical microenvironments. Nevertheless, many limitations persist in 3D or 4D culture systems, including difficulties in deciphering dynamic and reciprocal remodeling processes, as well as the spatiotemporal distributions of oxygen, nutrients, and metabolic waste. Here, we review 2D, 3D, and 4D culture systems, discuss the advantages and limitations of these techniques in modeling physiologically and pathologically relevant processes, and suggest directions for future research.

Intraoperative Neurophysiological Monitoring (IONM) is an indispensable surgical tool that offers invaluable insights into neurological function across a spectrum of anatomical areas. By comprehensively assessing the integrity of the brain, brainstem, spinal cord, cranial nerves, and peripheral nerves, IONM plays a pivotal role in guiding surgical decision-making and optimizing patient outcomes, particularly in the context of high-risk procedures. Intraoperative drugs, especially anesthetics and/or analgesics, differentially modulate neurophysiological monitoring, which remarkably affects the application of neurophysiological monitoring under specific conditions and indicates the neurobiological mechanisms of anesthetics/analgesics. This review will describe various neurophysiological modalities utilized in intraoperative procedures, each employing a wide variety of physiological principles; summarize the modulatory effects of anesthetics/analgesics on these neurophysiological monitoring parameters; and elucidate their underlying mechanisms, with a particular emphasis on evoked potentials. Insights gleaned from this review can inform strategies of anesthesia management for surgeries that require IONM and guide future investigations on the mechanisms of anesthesia/analgesia.

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