In vitro methods in autophagy research: Applications in neurodegenerative diseases and mood disorders

BackgroundAutophagy is a conserved physiological intracellular mechanism responsible for the degradation and recycling of cytoplasmic constituents (e.g., damaged organelles, and protein aggregates) to maintain cell homeostasis. Aberrant autophagy has been observed in neurodegenerative diseases, including Alzheimer’s Disease (AD), Parkinson’s Disease (PD), Amyotrophic Lateral Sclerosis (ALS), and Huntington’s Disease (HD), and recently aberrant autophagy has been associated with mood disorders, such as depression. Several in vitro methods have been developed to study the complex and tightly regulated mechanisms of autophagy. In vitro methods applied to autophagy research are used to identify molecular key players involved in dysfunctional autophagy and to screen autophagy regulators with therapeutic applications in neurological diseases and mood disorders. Therefore, the aims of this narrative review are (1) to compile information on the cell-based methods used in autophagy research, (2) to discuss their application, and (3) to create a catalog of traditional and novel in vitro methods applied in neurodegenerative diseases and depression.MethodsPubmed and Google Scholar were used to retrieve relevant in vitro studies on autophagy mechanisms in neurological diseases and depression using a combination of search terms per mechanism and disease (e.g., “macroautophagy” and “Alzheimer’s disease”). A total of 37 studies were included (14 in PD, 8 in AD, 5 in ALS, 5 in %, and 5 in depression).ResultsA repertoire of traditional and novel approaches and techniques was compiled and discussed. The methods used in autophagy research focused on the mechanisms of macroautophagy, microautophagy, and chaperone-mediated autophagy. The in vitro tools presented in this review can be applied to explore pathophysiological mechanisms at a molecular level and to screen for potential therapeutic agents and their mechanism of action, which can be of great importance to understanding disease biology and potential therapeutic options in the context of neurodegenerative disorders and depression.ConclusionThis is the first review to compile, discuss, and provide a catalog of traditional and novel in vitro models applied to neurodegenerative disorders and depression

Molecular Targets of Bis (7)-Cognitin and Its Relevance in Neurological Disorders: A Systematic Review

Background: The exact mechanisms involved in the pathogenesis of neurodegenerative conditions are not fully known. The design of drugs that act on multiple targets represents a promising approach that should be explored for more effective clinical options for neurodegenerative disorders. B7C is s synthetic drug that has been studied for over 20 years and represents a promising multi-target drug for the treatment of neurodegenerative disorders, such as AD.Aims: The present systematic review, thus, aims at examining existing studies on the effect of B7C on different molecular targets and at discussing the relevance of B7C in neurological disorders.Methods: A list of predefined search terms was used to retrieve relevant articles from the databases of Embase, Pubmed, Scopus, and Web of Science. The selection of articles was done by two independent authors, who were considering articles concerned primarily with the evaluation of the effect of B7C on neurological disorders. Only full-text articles written in English were included; whereas, systematic reviews, meta-analyses, book chapters, conference subtracts, and computational studies were excluded.Results: A total of 2,266 articles were retrieved out of which 41 articles were included in the present systematic review. The effect of B7C on molecular targets, including AChE, BChE, BACE-1, NMDA receptor, GABA receptor, NOS, and Kv4.2 potassium channels was evaluated. Moreover, the studies that were included assessed the effect of B7C on biological processes, such as apoptosis, neuritogenesis, and amyloid beta aggregation. The animal studies examined in the review focused on the effect of B7C on cognition and memory.Conclusions: The beneficial effects observed on different molecular targets and biological processes relevant to neurological conditions confirm that B7C is a promising multi-target drug with the potential to treat neurological disorders

The Effectiveness of Aromatherapy for Depressive Symptoms: A Systematic Review

Background. Depression is one of the greatest health concerns affecting 350 million people globally. Aromatherapy is a popular CAM intervention chosen by people with depression. Due to the growing popularity of aromatherapy for alleviating depressive symptoms, in-depth evaluation of the evidence-based clinical efficacy of aromatherapy is urgently needed. Purpose. This systematic review aims to provide an analysis of the clinical evidence on the efficacy of aromatherapy for depressive symptoms on any type of patients. Methods. A systematic database search was carried out using predefined search terms in 5 databases: AMED, CINHAL, CCRCT, MEDLINE, and PsycINFO. Outcome measures included scales measuring depressive symptoms levels. Results. Twelve randomized controlled trials were included and two administration methods for the aromatherapy intervention including inhaled aromatherapy (5 studies) and massage aromatherapy (7 studies) were identified. Seven studies showed improvement in depressive symptoms. Limitations. The quality of half of the studies included is low, and the administration protocols among the studies varied considerably. Different assessment tools were also employed among the studies. Conclusions. Aromatherapy showed potential to be used as an effective therapeutic option for the relief of depressive symptoms in a wide variety of subjects. Particularly, aromatherapy massage showed to have more beneficial effects than inhalation aromatherapy

Olfactory dysfunction: A plausible source of COVID-19-induced neuropsychiatric symptoms

Olfactory dysfunction and neuropsychiatric symptoms are commonly reported by patients of coronavirus disease 2019 (COVID-19), a respiratory infection caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Evidence from recent research suggests linkages between altered or loss of smell and neuropsychiatric symptoms after infection with the coronavirus. Systemic inflammation and ischemic injury are believed to be the major cause of COVID-19-related CNS manifestation. Yet, some evidence suggest a neurotropic property of SARS-CoV-2. This mini-review article summarizes the neural correlates of olfaction and discusses the potential of trans-neuronal transmission of SARS-CoV-2 or its particles within the olfactory connections in the brain. The impact of the dysfunction in the olfactory network on the neuropsychiatric symptoms associated with COVID-19 will also be discussed

Hippocampal Neurogenesis and Dendritic Plasticity Support Running-Improved Spatial Learning and Depression-Like Behaviour in Stressed Rats

Exercise promotes hippocampal neurogenesis and dendritic plasticity while stress shows the opposite effects, suggesting a possible mechanism for exercise to counteract stress. Changes in hippocampal neurogenesis and dendritic modification occur simultaneously in rats with stress or exercise; however, it is unclear whether neurogenesis or dendritic remodeling has a greater impact on mediating the effect of exercise on stress since they have been separately examined. Here we examined hippocampal cell proliferation in runners treated with different doses (low: 30 mg/kg; moderate: 40 mg/kg; high: 50 mg/kg) of corticosterone (CORT) for 14 days. Water maze task and forced swim tests were applied to assess hippocampal-dependent learning and depression-like behaviour respectively the day after the treatment. Repeated CORT treatment resulted in a graded increase in depression-like behaviour and impaired spatial learning that is associated with decreased hippocampal cell proliferation and BDNF levels. Running reversed these effects in rats treated with low or moderate, but not high doses of CORT. Using 40 mg/kg CORT-treated rats, we further studied the role of neurogenesis and dendritic remodeling in mediating the effects of exercise on stress. Co-labelling with BrdU (thymidine analog) /doublecortin (immature neuronal marker) showed that running increased neuronal differentiation in vehicle- and CORT-treated rats. Running also increased dendritic length and spine density in CA3 pyramidal neurons in 40 mg/kg CORT-treated rats. Ablation of neurogenesis with Ara-c infusion diminished the effect of running on restoring spatial learning and decreasing depression-like behaviour in 40 mg/kg CORT-treated animals in spite of dendritic and spine enhancement. but not normal runners with enhanced dendritic length. The results indicate that both restored hippocampal neurogenesis and dendritic remodelling within the hippocampus are essential for running to counteract stress

Y-Like Retinal Ganglion Cells Innervate the Dorsal Raphe Nucleus in the Mongolian Gerbil (Meriones unguiculatus)

Background: The dorsal raphe nucleus (DRN) of the mesencephalon is a complex multi-functional and multi-transmitter nucleus involved in a wide range of behavioral and physiological processes. The DRN receives a direct input from the retina. However little is known regarding the type of retinal ganglion cell (RGC) that innervates the DRN. We examined morphological characteristics and physiological properties of these DRN projecting ganglion cells. Methodology/Principal Findings: The Mongolian gerbils are highly visual rodents with a diurnal/crepuscular activity rhythm. It has been widely used as experimental animals of various studies including seasonal affective disorders and depression. Young adult gerbils were used in the present study. DRN-projecting RGCs were identified following retrograde tracer injection into the DRN, characterized physiologically by extracellular recording and morphologically after intracellular filling. The result shows that DRN-projecting RGCs exhibit morphological characteristics typical of alpha RGCs and physiological response properties of Y-cells. Melanopsin was not detected in these RGCs and they show no evidence of intrinsic photosensitivity. Conclusions/Significance: These findings suggest that RGCs with alpha-like morphology and Y-like physiology appear to perform a non-imaging forming function and thus may participate in the modulation of DRN activity which includes regulation of sleep and mood

Study of adult neurogenesis and molecular mechanism underlying sexual behavior in male rats following induction of depression-like behaviorand pharmacological treatment

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Exogenous neural stem cell transplantation for cerebral ischemia

Cerebral ischemic injury is the main manifestation of stroke, and its incidence in stroke patients is 70–80%. Although ischemic stroke can be treated with tissue-type plasminogen activator, its time window of effectiveness is narrow. Therefore, the incidence of paralysis, hypoesthesia, aphasia, dysphagia, and cognitive impairment caused by cerebral ischemia is high. Nerve tissue regeneration can promote the recovery of the aforementioned dysfunction. Neural stem cells can participate in the reconstruction of the damaged nervous system and promote the recovery of nervous function during self-repair of damaged brain tissue. Neural stem cell transplantation for ischemic stroke has been a hot topic for more than 10 years. This review discusses the treatment of ischemic stroke with neural stem cells, as well as the mechanisms of their involvement in stroke treatment

Visual response patterns of Y cells before and after synaptic transmission blockade.

<p>The synaptic blocker cocktail consisted of a mixture of excitatory and inhibitory neurotransmitter blockers including L-(+)-2-Amino-4-phosphonobutyric acid (AP-4, 100 µM), 6,7-Dinitroquinoxaline-2,3-dione (DNQX, 20 µM), DL-2-amino-5-phosphonovaleric acid (AP5, 50 µM), Picrotoxin (50 µM ) Strychnine (0.3 µM), and hexamethonimm bromide (200 µM) was added to the oxygenated Ames' medium. (<b>A</b>) visual responses of an ON center (upper) and (<b>C</b>) an OFF center (lower) DRN-projecting RGCs before synaptic transmission blockade. (<b>B</b>) and (<b>D</b>) response patterns of the cells after synaptic transmission blockade. The retinal irradiance of the stimuli was 6.4×10¹³ photons/cm²/sec, λ = 475 nm, and stimulation duration was 20 seconds.</p