Brain-derived neurotrophic factor interplay with oxidative stress: neuropathology approach in potential biomarker of Alzheimer’s disease

ABSTRACT The aging population poses a serious challenge concerning an increased prevalence of Alzheimer’s disease (AD) and its impact on global burden, morbidity, and mortality. Oxidative stress, as a molecular hallmark that causes susceptibility in AD, interplays to other AD-related neuropathology cascades and decreases the expression of central and circulation brain-derived neurotrophic factor (BDNF), an essential neurotrophin that serves as nerve development and survival, and synaptic plasticity in AD. By its significant correlation with the molecular and clinical progression of AD, BDNF can potentially be used as an objectively accurate biomarker for AD diagnosis and progressivity follow-up in future clinical practice. This comprehensive review highlights the oxidative stress interplay with BDNF in AD neuropathology and its potential use as an AD biomarker

LIGHT EXPOSURE’S EFFECTS ON INACTIVE STATE DURATION AND SLEEP LATENCY IN ZEBRAFISH (DANIO RERIO) LARVAE INSOMNIA MODEL

Background: Insomnia is defined as difficulty falling or staying asleep or a sleep state that cannot restore the body's condition. The zebrafish (Danio rerio) is a vertebrate model that has been extensively studied to study sleep and neurological disorders. One of the most widely used methods to examine the effect of the light-dark cycle on the circadian system is by exposing animals and humans to pulse wave light. Objective: To see the effect of light exposure on zebrafish larvae by looking at inactive state duration and sleep latency in zebrafish (Danio rerio) larvae insomnia model. Methods: This study used four groups of zebrafish larvae i.e : (1) normal group (2) minutes of light exposure and 2 minutes off (2/2)), (3) Four minutes of light exposure and 1 minute off (4/1), and (4)  24 hours on (24/0). Observation of larval movement was carried out on 5, 6, and 7 dpf (day post fertilization). Observation time was 30 minutes before and after turned off of light exposure. Results: There were significant differences on days 5, 6, and 7 between the normal group and the three light treatment groups on inactive state duration and sleep latency in dark and light conditions with p-values (p<0.05) and (p< 0.031), but there was no significant difference among groups of light exposure 2 minutes on 2 minutes off, 4 minutes on 1 minute off, and 24 hours on. The 24-hour on treatment showed the most inactive state duration among the light treatments, while the sleep latency was found in the 24-hour treatment. Conclusion: Light treatment of 2 minutes on 2 minutes off, 4 minutes on 1 minute off, and 24 hours on can cause insomnia, but the most substantial insomnia effect is obtained from the 24-hour treatment

Pengaruh Ekstrak Pegagan (Centella Asiatica) Terhadap Ekspresi Reseptor Dopamin Pada Ikan Zebra (Danio Rerio) Model Insomnia

nsomnia adalah suatu kondisi seseorang mengalami gangguan memulai tidur atau terjaga dalam jangka waktu yang lama. Kesulitan tidur ini biasanya terjadi minimal 3x dalam satu minggu dan menjadi masalah minimal 1 bulan (Roth, 2007). Beberapa terapi telah digunakan untuk mengobati insomnia, namun sampai saat ini masih belum memuaskan dan memiliki efek samping seperti pusing, mual, dan kelelahan. Centella asiatica atau pegagan merupakan tumbuhan tropis yang memiliki efek pada berbagai macam penyakit neurologis. Pegagan memiliki berbagai efek farmakologis antara lain efek antiinflamasi, peremajaan, perbaikan stress dan perbaikan intelegensia. Saat ini banyak model hewan telah dikembangkan untuk mempelajari gangguan tidur salah satunya adalah ikan Zebra. Ikan Zebra (Danio rerio) meperlihatkan model tidur pada vertebrata. Hasil dari paparan pegagan terhadap ikan zebra model insomnia dapat memperbaiki kondisi insomnia dengan meningkatkan DRD 2 dan menurunkan DRD 1 melalui pengukuran qRT PCR, dimana DRD 1 berperan dalam proses arousal dan DRD 2 memicu proses tidur. Kandungan Asiatic acid pada pegagan dapat membuat efek anti inflamasi yang bekerja pada penghambatan MAPK dan juga sekaligus juga peremajaan pada neuron GABA pemicu tidur. Dapat disimpulkan bahwa ekstrak pegagan (Centella asiatica) cdapat memperbaiki kondisi insomnia dengan menurunkan regulasi DRD 1 dan meningkatkan DRD 2 pada larva ikan zebra model insomni

Folic Acid Treatment for Patients with Vascular Cognitive Impairment: A Systematic Review and Meta-Analysis

Background: As the life expectancy of elderly people has drastically increased, the incidence of cardiovascular and cerebrovascular diseases in this population has proportionally grown. Vascular cognitive impairment refers to all forms of cognitive disorder associated with cerebrovascular disease. Homocysteine has recently been recognized as a contributor to the pathomechanisms involved in cognitive impairment. B vitamins, such as folic acid, are known to be effective in lowering homocysteine levels. Methods: We conducted a systematic review and meta-analysis of research on folic acid treatments for vascular cognitive impairment. Only randomized controlled trials studies that compared the efficacy of folic acid with placebo or other interventions were considered, irrespective of publication status, year of publication, and languages. Two independent reviewers searched the Medline via Ovid, EMBASE, and Cochrane Central Register of Controlled Trials (Central) journal databases up to July 2021 and independently appraised the included studies. We used mean difference outcome with 95% confidence intervals (CI) to calculate the change of Mini-Mental State Examination, cognitive function domain, and concentration of homocysteine. Results: We found 3 studies comparing folic acid with placebo and 1 study comparing folic acid with other interventions. There is only slight evidence that the Mini-Mental State Examination score in patients who received folic acid increased 0.3 point higher compared with the placebo group after 24 months (95% CI =-0.12 to 0.37; P =. 31). There is very strong evidence that the concentration of homocysteine in the folic acid group became 6.16 μmol/L lower compared with the placebo group after 6 months (95% CI = 2.32 to 8.21 lower; P<.001). Conclusions: Our review shows the effectiveness of folic acid in lowering the plasma homocysteine concentration after 6 months compared with placebo. However, this effect was not accompanied by improvement in cognitive function

Enucleation Induces Parvalbumin and Glial Fibrillary Acidic Protein, but Not Calbindin D28k Protein Expression in Superior Colliculus of Wistar Rats

Background: It is known that eye enucleation causes various morphological and functional alterations in the central nervous system (CNS). The purpose of this study was to examine the sub-chronic effects of monocular enucleation on the distribution of the calcium binding proteins calbindin D28k (CB) and parvalbumin (PV) as well as the glial fibrillary acidic protein (GFAP) immunoreactivity in the superior colliculus (SC) of Wistar rats. Materials and Methods: Thirty young adult (8 weeks) male Wistar rats from SLC (Shizuoka, Japan), weighing 200-250 grams, were housed in separate cages under controlled conditions with a constant temperature kept in 12:12 light/dark cycle and ad libitum water and food. In this study the rats were divided into two groups, a control and an enucleated groups. The experimental group received unilateral eye enucleation and was allowed 1, 4 or 12 weeks recovery before sacrificed. Results: Unilateral enucleation over a period of 1 week or more caused a decrease in the number CB-immunoreactive (CBIR) neurons. This loss was associated with an increase in GFAP-IR astrocytes in the superficial gray layer and the optic layer of the SC with contralateral side predominance. In addition, the CB-IR neurons illustrated a smaller soma and poor dendritic arborization. Conversely, the GFAP-IR astrocytes were hypertrophied with longer foot processes on the contralateral side of enucleation. Interestingly, the number of PV-IR neurons was elevated for up to 4 weeks in enucleated rats versus shamoperated rats. Conclusion: This study demonstrates the importance of calcium-binding protein homeostasis and reversible glial response for maintaining variability of neuronal function in sub-cortical visual centers following optic nerve deafferentation. Keywords: enucleation, superior colliculus, calbindin D28k, parvalbumin, glial fibrillary acidic protei

Repetitive intermittent hypoxia induces respiratory and somatic motor recovery after chronic cervical spinal injury

Spinal injury disrupts connections between the brain and spinal cord, causing life-long paralysis. Most spinal injuries are incomplete, leaving spared neural pathways to motor neurons that initiate and coordinate movement. One therapeutic strategy to induce functional motor recovery is to harness plasticity in these spared neural pathways. Chronic intermittent hypoxia (CIH) (72 episodes per night, 7 nights) increases synaptic strength in crossed spinal synaptic pathways to phrenic motoneurons below a C2 spinal hemisection. However, CIH also causes morbidity (e.g., high blood pressure, hippocampal apoptosis), rendering it unsuitable as a therapeutic approach to chronic spinal injury. Less severe protocols of repetitive acute intermittent hypoxia may elicit plasticity without associated morbidity. Here we demonstrate that daily acute intermittent hypoxia (dAIH; 10 episodes per day, 7 d) induces motor plasticity in respiratory and nonrespiratory motor behaviors without evidence for associated morbidity. dAIH induces plasticity in spared, spinal pathways to respiratory and nonrespiratory motor neurons, improving respiratory and nonrespiratory (forelimb) motor function in rats with chronic cervical injuries. Functional improvements were persistent and were mirrored by neurochemical changes in proteins that contribute to respiratory motor plasticity after intermittent hypoxia (BDNF and TrkB) within both respiratory and nonrespiratory motor nuclei. Collectively, these studies demonstrate that repetitive acute intermittent hypoxia may be an effective and non-invasive means of improving function in multiple motor systems after chronic spinal injury