Prevalence Estimates of Neurodevelopmental Disorders (NDD) in a South Indian Population.

Background: Neurodevelopmental disorders (NDDs) represent a significant public health concern globally, yet comprehensive prevalence data in India, a nation with 1.4 billion inhabitants, remains scarce. Limited systematic investigations have hindered effective public health planning.

Computationally designed multi-epitope vaccine construct targeting the SARS-CoV-2 spike protein elicits robust immune responses in silico.

Our research is driven by the need to design an advanced multi-epitope vaccine construct (MEVC) using the S-protein of SARS-CoV-2 to combat the emergence of new variants. Through rigorous computational screening, we have identified linear and discontinuous B-cell epitopes, CD8 + and CD4 + T-cell epitopes, ensuring extensive MEVC coverage across 90.03% of the global population.

Quality of life and Concerns of Parkinson's Disease Patients and their Caregivers during COVID-19 Pandemic: An Indian Study.

Objectives: Parkinson's disease (PD) patients have suffered during the coronavirus disease 2019 pandemic, with worsening of both motor and nonmotor symptoms. We conducted this study to evaluate the quality of life (QoL) and concerns of PD patients and their caregivers.

Methods: The study was conducted in mixed method, where the baseline data was taken by face-to-face interview during the unlock phase of December 2020 to March 2021, when there was no lockdown.

Efficacy of defensins as neutralizing agents against the deadly SARS-CoV-2.

SARS-CoV-2 infection causes asymptomatic to severe human respiratory diseases. Vaccinations are effective only to a certain extent, and the disease recurs with milder symptoms even after booster doses. Hence, we hypothesize that antiviral therapy in conjunction with vaccination is the need of the hour for containing the disease.

Neuro-nutraceuticals: Natural products nourish the brain but be aware of contrary effects.

In this Special Issue on "Nutraceuticals: Molecular and Functional Insights into how Natural Products Nourish the Brain", the editors bring together contributions from experts in nutraceutical research to provide a contemporary overview of how select chemically identified molecules from natural products can beneficially affect brain function at the molecular level. Other contributions address the holistic benefit of herbal medicines and their multi-targeted actions, which improve brain function in diverse cellular and animal models of brain injury. Not only are new targets for nutraceuticals reported, but their benefits on neurobehavioural problems are elucidated in conditions as diverse as obesity and menopause.

Nutraceutical based SIRT3 activators as therapeutic targets in Alzheimer's disease.

Alzheimer's disease (AD) is the most common neurodegenerative disease, and its incidence is increasing worldwide with increased lifespan. Currently, there is no effective treatment to cure or prevent the progression of AD, which indicates the need to develop novel therapeutic targets and agents. Sirtuins, especially SIRT3, a mitochondrial deacetylase, are NAD-dependent histone deacetylases involved in aging and longevity.

The light at the end of the tunnel gets vivid for spinal muscular atrophy: An Editorial Highlight for "Cerebrospinal fluid proteomic profiling in nusinersen-treated patients with spinal muscular atrophy" on page 650.

Kessler et al. in this current issue have attempted to discern biomarker(s) for spinal muscular atrophy (SMA) by assessing alterations in cerebrospinal fluid (CSF) proteomics profile. Recently, antisense oligonucleotide (nusinersen) therapy is shown to mitigate pathologies and provide behavioral improvements in patients.

Gender-Specific Effect of 5-HT and 5-HIAA on Threshold Level of Behavioral Symptoms and Sex-Bias in Prevalence of Autism Spectrum Disorder.

Platelet hyperserotonemia in a subset of Autism Spectrum Disorder (ASD) probands, efficacy of selective serotonin reuptake inhibitors (SSRIs) in reducing behavioral deficits and gender-bias in normal serotonin (5-hydroxy tryptamine or 5-HT) synthesis suggest disruption in stringent regulation of serotonin metabolism in ASD. Therefore, we investigated the changes in 5-HT and 5-hydroxy indole acetic acid (5-HIAA) in ASD probands to assess its effect on the behavior of male and female probands. ASD cases ( = 215) were examined using childhood autism rating scale (CARS).

1-Methyl-4-Phenylpyridinium-Induced Death of Differentiated SH-SY5Y Neurons Is Potentiated by Cholesterol.

Background/aims: Hypercholesterolemia is recently considered a risk factor for Parkinson's disease (PD), the most consistent neurodegenerative movement disorder. The study aimed to investigate the effect of exogenous cholesterol on 1-methyl-4-phenylpyridinium (MPP) parkinsonian neurotoxin-induced cell death, loss of mitochondrial membrane potential, and dopaminergic deficiency in a cellular model of PD.

Methods: Cholesterol (50 μM) when added in the culture media alone or in combination with MPP was studied in SH-SY5Y neuroblastoma cells.

Nimodipine attenuates the parkinsonian neurotoxin, MPTP-induced changes in the calcium binding proteins, calpain and calbindin.

We have recently demonstrated neuroprotective abilities of nimodipine, an L-type voltage dependent calcium channel (VDCC) blocker in cellular and animal models of Parkinson's disease (PD). To understand the calcium regulatory mechanisms in the disease pathogenesis, the present study examined calcium regulatory proteins calbindin and calpain mRNA and protein levels employing quantitative PCR and western blot in 1-methyl-4-phenyl pyridinium ion (MPP)-treated SH-SY5Y cell lines and in the striatum of mice treated with 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP). mRNA and protein levels of calbindin were lower, while that of calpain were higher in MPP-treated SH-SY5Y cells and MPTP-treated mouse striatum as compared to their respective controls.

Pilot study indicate role of preferentially transmitted monoamine oxidase gene variants in behavioral problems of male ADHD probands.

Background: Attention deficit hyperactivity disorder (ADHD) is an etiologically complex childhood onset neurobehavioral disorder characterized by age-inappropriate inattention, hyperactivity, and impulsivity. Symptom severity varies widely and boys are diagnosed more frequently than girls. ADHD probands were reported to have abnormal transmissions of dopamine, serotonin, and/or noradrenaline.

Can Cyclic Nucleotide Phosphodiesterase Inhibitors Be Drugs for Parkinson's Disease?

Parkinson's disease (PD) has no known cure; available therapies are only capable of offering temporary, symptomatic relief to the patients. Varied therapeutic strategies that are clinically used for PD are pharmacological therapies including dopamine replacement therapies (with or without adjuvant), postsynaptic dopamine receptor stimulation, dopamine catabolism inhibitors and also anticholinergics. Surgical therapies like deep brain stimulation and ablative surgical techniques are also employed.

Low Levels of Prohibitin in Substantia Nigra Makes Dopaminergic Neurons Vulnerable in Parkinson's Disease.

Since substantia nigra (SN) and ventral tegmental area (VTA) dopaminergic neurons are, respectively, susceptible or largely unaffected in Parkinson's disease (PD), we searched for protein(s) that regulates this differential sensitivity. Differentially, expressed proteins in SN and VTA were investigated employing two-directional gel electrophoresis- matrix-assisted laser desorption ionization time of flight (MALDI-TOF-TOF) analyses. Prohibitin, which is involved in mitochondrial integrity, was validated using immunoblot, qRT-PCR, and immunohistochemistry in normal mice as well as 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP)-model, PD postmortem human brains, and PD cybrids.

Attention deficit-hyperactivity disorder suffers from mitochondrial dysfunction.

Background: Pathophysiology of attention-deficit hyperactivity disorder (ADHD) is not known, and therefore the present study investigated mitochondrial defects, if any in cybrids created from patients and control population.

Methods: To investigate mitochondrial pathology in ADHD, cybrids cell lines were created from ADHD probands and controls by fusing their platelets with ρ-cells prepared from SH-SY5Y neuroblastoma cell line. Cellular respiration, oxidative stress, mitochondrial membrane potential and morphology were evaluated employing oxygraph, mitochondria-specific fluorescence staining and evaluation by FACS, and immunocytochemistry.

Nimodipine, an L-type calcium channel blocker attenuates mitochondrial dysfunctions to protect against 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine-induced Parkinsonism in mice.

Parkinson's disease (PD), the most common progressive neurodegenerative movement disorder, results from loss of dopaminergic neurons of substantia nigra pars compacta. These neurons exhibit Cav1.3 channel-dependent pacemaking activity.

Genetic variants of MAOB affect serotonin level and specific behavioral attributes to increase autism spectrum disorder (ASD) susceptibility in males.

Serotonergic system participates in various developmental processes and modulation of behaviour. Autism Spectrum Disorder (ASD) is characterized by a range of behavioral symptoms scaling from mild to severe. Abnormal 5-HT synthesis and signalling, platelet hyperserotonemia and amelioration of repetitive behaviours by SSRI are some of the key findings, which reinforced the hypothesis that serotonergic genes might act as ASD susceptible genes.

Monoamine oxidase B gene variants associated with attention deficit hyperactivity disorder in the Indo-Caucasoid population from West Bengal.

Background: Attention deficit hyperactivity disorder (ADHD) is characterized by symptoms of inattention, excessive motor activity and impulsivity detected mostly during childhood. These traits are known to be controlled by monoamine neurotransmitters, chiefly dopamine, serotonin and norepinephrine. Monoamine oxidase A (MAOA) and B (MAOB), two isoenzymes bound to the outer membrane of mitochondria, are involved in the degradation of monoamines and were explored for association with ADHD in different ethnic groups.

Aging and Neurodegeneration: A Tangle of Models and Mechanisms.

The research on aging and age-related diseases, especially the neurodegenerative diseases, is on the fast track. However, the results have so far not been translated to actual benefit for the patients in terms of treatment or diagnosis of age-related degenerative diseases including those of the CNS. As far as the prevention of the cognitive decline during non-pathological aging is concerned, there is nothing much to offer other than calorie restriction and physical exercise.

Neuro-nutraceuticals: The path to brain health via nourishment is not so distant.

In this Special Issue on "Nutraceuticals: Molecular and Functional Insights into how Natural Products Nourish the Brain", the editors bring together contributions from experts in nutraceutical research to provide a contemporary overview of how select chemically identified molecules can beneficially affect brain function at the molecular level. Other contributions address key emergent issues such as bioavailability, formulation, blood brain permeability, neuronal health and inflammation that impact upon how nutraceuticals ultimately leverage the brain to function better. Whilst nutraceutical is used as marketing term, it has no regulatory definition, and there is a continuing need for licensing authorities to ensure that adequate guidelines exist pertinent to the safety to guide consumers internationally.

Tea and Parkinson's disease: Constituents of tea synergize with antiparkinsonian drugs to provide better therapeutic benefits.

The major neurodegenerative movement disorder Parkinson's disease (PD) is characterized by rest-tremor, akinesia, rigidity and inability to initiate movements. PD syndromes result from excessive loss of dopamine from the forebrain striatal region, due to dopaminergic neuronal death in the midbrain substantia nigra pars compacta. PD with multifactorial etiology is believed to ideally require a drug or different drugs that act(s) at multiple sites of action for symptomatic relief.

Mitochondrial Deficits Accompany Cognitive Decline Following Single Bilateral Intracerebroventricular Streptozotocin.

Background: Bilateral intracerebroventricular (ICV) administration of streptozotocin (STZ) causes Alzheimer's disease (AD)-type neurodegeneration in rats. The model is increasingly used for investigating pathology and therapeutic strategies for AD.

Objective: The present study investigated cognitive abilities in rats infused with STZ-ICV in relation to hippocampal and cortical mitochondrial functions during a period of 60 days.

Serotonin mediated immunoregulation and neural functions: Complicity in the aetiology of autism spectrum disorders.

Serotonergic system has long been implicated in the aetiology of autism spectrum disorders (ASD), since platelet hyperserotonemia is consistently observed in a subset of autistic patients, who respond well to selective serotonin reuptake inhibitors. Apart from being a neurotransmitter, serotonin functions as a neurotrophic factor directing brain development and as an immunoregulator modulating immune responses. Serotonin transporter (SERT) regulates serotonin level in lymphoid tissues to ensure its proper functioning in innate and adaptive responses.

Melatonin enhances L-DOPA therapeutic effects, helps to reduce its dose, and protects dopaminergic neurons in 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine-induced Parkinsonism in mice.

L-3,4-dihydroxyphenylalanine (L-DOPA) reduces symptoms of Parkinson's disease (PD), but suffers from serious side effects on long-term use. Melatonin (10-30 mg/kg, 6 doses at 10 hr intervals) was investigated to potentiate L-DOPA therapeutic effects in 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP)-induced parkinsonism in mice. Striatal tyrosine hydroxylase (TH) immunoreactivity, TH, and phosphorylated ser 40 TH (p-TH) protein levels were assayed on 7th day.

Embryonic stem cells derived neuron transplantation recovery in models of parkinsonism in relation to severity of the disorder in rats.

6-Hydroxydopamine (6-OHDA)- and 1-methyl-4-phenylpyridinium (MPP(+))-induced hemi-parkinsonism was investigated in relation to the severity of the disorder in terms of behavioral disability and nigral neuronal loss and recovery regarding the number of stem cell-derived neurons transplanted in the striatum. Intra-median forebrain bundle infusion of the parkinsonian neurotoxins and intra-striatal transplantation of differentiated embryonic stem cells (ESCs) were carried out by rat brain stereotaxic surgery. The severity of the disease was determined using the number of amphetamine- or apomorphine-induced rotations, striatal dopamine levels as estimated by high-performance liquid chromatography (HPLC)-electrochemistry, and the number of surviving tyrosine hydroxylase immunoreactive dopaminergic neurons in the substantia nigra pars compacta.