Leveraging AI for the diagnosis and treatment of autism spectrum disorder: Current trends and future prospects.

The integration of artificial intelligence (AI) into the diagnosis and treatment of autism spectrum disorder (ASD) represents a promising frontier in healthcare. This review explores the current landscape and future prospects of AI technologies in ASD diagnostics and interventions. AI enables early detection and personalized assessment of ASD through the analysis of diverse data sources such as behavioural patterns, neuroimaging, genetics, and electronic health records. Machine learning algorithms exhibit high accuracy in distinguishing ASD from neurotypical development and other developmental disorders, facilitating timely interventions. Furthermore, AI-driven therapeutic interventions, including augmentative communication systems, virtual reality-based training, and robot-assisted therapies, show potential in improving social interactions and communication skills in individuals with ASD. Despite challenges such as data privacy and interpretability, the future of AI in ASD holds promise for refining diagnostic accuracy, deploying telehealth platforms, and tailoring treatment plans. By harnessing AI, clinicians can enhance ASD care delivery, empower patients, and advance our understanding of this complex condition.

Agmatine modulation of gut-brain axis alleviates dysbiosis-induced depression-like behavior in rats.

Depression is a global health concern affecting nearly 280 million individuals. It not only imposes a significant burden on economies and healthcare systems but also manifests complex physiological connections and consequences. Agmatine, a putative neuromodulator derived primarily from beneficial gut microbes specially Lactobacillus, has emerged as a potential therapeutic agent for mental health. The microbiota-gut-brain axis is involved in the development of depression through the peripheral nervous system, endocrine system, and immune system and may be a key factor in the effect of agmatine. Therefore, this study aimed to investigate the potential mechanism of agmatine in antibiotic-induced dysbiosis and depression-like behavior in rats, focusing on its modulation of the gut-brain axis. Depression-like behavior associated with dysbiosis was induced through a seven-day regimen of the broad-spectrum antibiotic, comprising ampicillin and metronidazole and validated through microbial, biochemical, and behavioral alterations. On day 8, antibiotic-treated rats exhibited loose fecal consistency, altered fecal microbiota, and depression-like behavior in forced swim test. Pro-inflammatory cytokines were elevated, while agmatine and monoamine levels decreased in the hippocampus and prefrontal cortex. Antibiotic administration disrupted tight junction proteins in the ileum, affecting gut architecture. Oral administration of agmatine alone or combined with probiotics significantly reversed antibiotic-induced dysbiosis, restoring gut microbiota and mitigating depression-like behaviors. This intervention also restored neuro-inflammatory markers, increased agmatine and monoamine levels, and preserved gut integrity. The study highlights the regulatory role of endogenous agmatine in the gut-brain axis in broad-spectrum antibiotic induced dysbiosis and associated depression-like behavior.

Navigating the intersection: Diabetes and Alzheimer's intertwined relationship.

Alzheimer's disease (AD) and Diabetes mellitus (DM) exhibit comparable pathophysiological pathways. Genetic abnormalities in APP, PS-1, and PS-2 are linked to AD, with diagnostic aid from CSF and blood biomarkers. Insulin dysfunction, termed "type 3 diabetes mellitus" in AD, involves altered insulin signalling and neuronal shrinkage. Insulin influences beta-amyloid metabolism, exacerbating neurotoxicity in AD and amyloid production in DM. Both disorders display impaired glucose transporter expression, hastening cognitive decline. Mitochondrial dysfunction and Toll-like receptor 4-mediated inflammation worsen neurodegeneration in both diseases. ApoE4 raises disease risk, especially when coupled with dyslipidemia common in DM. Targeting shared pathways like insulin-degrading enzyme activation and HSP60 holds promise for therapeutic intervention. Recognizing these interconnected mechanisms underscores the imperative for developing tailored treatments addressing the overlapping pathophysiology of AD and DM, offering potential avenues for more effective management of both conditions.

Agmatine alleviates ethanol withdrawal-associated cognitive impairment and neurochemical imbalance in rats.

The present study aimed to investigate the role of agmatine in the neurobiology underlying memory impairment during ethanol withdrawal in rats. Sprague-Dawley rats were subjected to a 21-day chronic ethanol exposure regimen (2.4 % w/v ethanol for 3 days, 4.8 % w/v for the next 4 days, and 7.2 % w/v for the following 14 days), followed by a withdrawal period. Memory impairment was assessed using the passive avoidance test (PAT) at 24, 48, and 72 h post-withdrawal. The ethanol-withdrawn rats displayed a significant decrease in step-through latency in the PAT, indicative of memory impairment at 72 h post-withdrawal. However, administration of agmatine (40 µg/rat) and its modulators (L-arginine, arcaine, and amino-guanidine) significantly increases the latency time in the ethanol-withdrawn rats, demonstrating the attenuation of memory impairment. Further, pretreatment with imidazoline receptor agonists enhances agmatine's effects, while antagonists block them, implicating imidazoline receptors in agmatine's actions. Neurochemical analysis in ethanol-withdrawn rats reveals dysregulated glutamate and GABA levels, which was attenuated by agmatine and its modulators. By examining the effects of agmatine administration and modulators of endogenous agmatine, the study aimed to shed light on the potential therapeutic implications of agmatinergic signaling in alcohol addiction and related cognitive deficits. Thus, the present findings suggest that agmatine administration and modulation of endogenous agmatine levels hold potential as therapeutic strategies for managing alcohol addiction and associated cognitive deficits. Understanding the neurobiology underlying these effects paves the way for the development of novel interventions targeting agmatinergic signaling in addiction treatment.

Molecular understanding of ER-MT communication dysfunction during neurodegeneration.

Biological researchers are seeing organelles in a new light. These cellular entities have been believed to be singular and distinctive structures that performed specialized purposes for a very long time. But in recentpast years, scientists have learned that organelles become dynamic and make physical contact. Additionally, Biological processes are regulated by organelles interactions and its alteration play an important role in cell malfunctioning and several pathologies, including neurodegenerative diseases. Mitochondrial-ER contact sites (MERCS) have received considerable attention in the domain of cell homeostasis and dysfunction, specifically in the area of neurodegeneration. This is largely due to the significant role of this subcellular compartment in a diverse array of vital cellular functions, including Ca2+ homeostasis, transport, bioenergetics and turnover, mitochondrial dynamics, apoptotic signaling, ER stress, and inflammation. A significant number of disease-associated proteins were found to physically interact with the ER-Mitochondria (ER-MT) interface, causing structural and/or functional alterations in this compartment. In this review, we summarize current knowledge about the structure and functions of the ER-MT contact sites, as well as the possible repercussions of their alteration in notable neurodegenerative disorders such as Alzheimer's disease, Parkinson's disease, amyotrophic lateral sclerosis, and fronto-temporal dementia. The constraints and complexities in defining the nature and origin of the highlighted defects in ER-MT communication, as well as their concise contribution to the neurodegenerative process, are illustrated in particular. The possibility of using MERCS as a potential drug target to prevent neuronal damage and ultimately neurodegeneration is the topic of our final discussion.

Mitophagy regulation in aging and neurodegenerative disease.

Mitochondria are the primary cellular energy generators, supplying the majority of adenosine triphosphate through oxidative phosphorylation, which is necessary for neuron function and survival. Mitophagy is the metabolic process of eliminating dysfunctional or redundant mitochondria. It is a type of autophagy and it is crucial for maintaining mitochondrial and neuronal health. Impaired mitophagy leads to an accumulation of damaged mitochondria and proteins leading to the dysregulation of mitochondrial quality control processes. Recent research shows the vital role of mitophagy in neurons and the pathogenesis of major neurodegenerative diseases. Mitophagy also plays a major role in the process of aging. This review describes the alterations that are being caused in the mitophagy process at the molecular level in aging and in neurodegenerative diseases, particularly Alzheimer's, Parkinson's, and Huntington's diseases and amyotrophic lateral sclerosis, also looks at how mitophagy can be exploited as a therapeutic target for these diseases.

Possible involvement of agmatine in neuropharmacological actions of metformin in diabetic mice.

The risk of psychiatric and neurological disorders is significantly higher in patients with diabetes mellitus. Diabetic patients are more susceptible to depression, anxiety and memory impairment as compared with non-diabetic individuals. Metformin, a biguanide used for the management of type 2 diabetes mellitus (T2DM), promotes neurogenesis, enhances spatial memory function and protects the brain against oxidative imbalance beyond its effect on glucose metabolism. However, the exact mechanism of its neuropharmacological actions in T2DM is not known. We investigated the role of the agmatinergic system in neuropharmacological actions of metformin in diabetic mice. Diabetes was induced by the streptozotocin (STZ) injection and confirmed by high blood glucose levels. After 28 days, STZ treated mice exhibited memory impairment in radial arm maze, depression-like behavior in forced swim test and anxiety-like behavior in elevated plus maze along with increased expression of pro-inflammatory cytokines like TNF-α, IL-1ß, IL-6, IL-10 also, reduced agmatine and BDNF levels in the hippocampus and prefrontal cortex compared to the control animals. Metformin and agmatine alone or in combination, by once-daily administration during 14-27 day of the protocol significantly reversed the STZ induced high blood glucose levels, memory impairment, depression and anxiety-like behaviors. It also reduced neuro-inflammatory markers and increased agmatine and BDNF levels in the hippocampus and prefrontal cortex. The present study suggests the importance of endogenous agmatine in the neuropharmacological action of metformin in diabetic mice. The data projects agmatine and metformin combination as a potential therapeutic strategy for diabetes associated memory impairment, depression, anxiety, and other comorbidities.

Agmatine improves the behavioral and cognitive impairments associated with chronic gestational ethanol exposure in rats.

Chronic maternal ethanol exposure leads to poor intelligence, impaired cognition and array of neurological symptoms in offsprings and commonly referred as fetal alcohol spectrum disorder (FASD). Despite high prevalence and severity, the neurochemical basis of FASD remains largely unexplored. The present study evaluated the pharmacological effects of agmatine in cognitive deficits associated with FAS in rat's offsprings prenatally exposed to alcohol. Pregnant rats received ethanol in liquid modified diet during the entire gestational period of 21 days. Offsprings were treated with agmatine (20-80 mg/Kg, i.p.) during early postnatal days (PND: 21-35) and subsequently evaluated for anxiety in elevated plus maze (EPM), depression in forced swim test (FST) and learning and memory in Morris's water maze (MWM) during post adolescent phase. Hippocampal agmatine, BDNF, TNF-α and IL-6 levels were also analyzed in prenatally ethanol exposed pups. Offsprings prenatally exposed to ethanol demonstrated delayed righting reflex, reduced exploratory behavior along with anxiety, depression-like behavior and impaired memory. These behavioral abnormalities were correlated with a significant reduction in hippocampal agmatine and BDNF levels and elevation in TNF-α and IL-6 immunocontent. Chronic agmatine (40 and 80 mg/Kg, i.p.) administration for 15 days (PND: 21-35), improved entries and time spent in open arm of EPM, decreased immobility time in FST. It also reduced latency to reach the platform location; increased the number of entries, time spent in platform quadrant and also number of crossing over platform quadrant when subjected to MWM test in prenatally ethanol exposed offsprings. This study provides functional evidences for the therapeutic potential of agmatine in cognitive impairment and other neurological complications associated with FASD.

Involvement of agmatine in antidepressant-like effect of HMG-CoA reductase inhibitors in mice.

3-Hydroxy-3-methyl-glutaryl-co-enzyme-A (HMG-CoA) reductase inhibitors (statins) are popularly used for the treatment of obesity and hypercholesterolemia with established safety profile. Statins exhibits a wide range of neurobehavioral effects in addition to their peripheral actions, and may be beneficial in treatment of psychiatric conditions. Present study investigated the role of agmatine and imidazoline receptors in antidepressant-like effect of statins in mouse forced swimming test (FST). The antidepressant-like effect of atorvastatin (5 mg/kg, p.o.) and simvastatin (10 mg/kg, p.o.) was potentiated by pretreatment with agmatine (5 mg/kg, i.p.) as well as the drugs known to increase endogenous agmatine levels in brain viz., L-arginine (40 µg/mouse, i.c.v.), an agmatine biosynthetic precursor; arcaine (50 µg/mouse, i.c.v), agmatinase inhibitor; and aminoguanidine (6.5 µg/mouse, i.c.v.), a diamine oxidase inhibitor. Further, both the statins increased agmatine levels within hippocampus and prefrontal cortex. Conversely, prior administration of I1 receptor antagonist, efaroxan (1 mg/kg, i.p.) and I2 receptor antagonist, idazoxan (0.25 mg/kg, i.p.) blocked the antidepressant-like effect of statins and their synergistic combination with agmatine. These results demonstrate the involvement of agmatine and imidazoline receptors in antidepressant-like effect of statins and suggest as a potential therapeutic target for the treatment of depressive disorders.