The implementation and effectiveness of Integrated Psychological Therapy (IPT) in chronic middle-aged inpatients with schizophrenia.

Introduction: Cognitive rehabilitation is essential for schizophrenia treatment since it improves function. Moreover, the relationship between cognitive rehabilitation and functioning is significantly affected by negative symptoms and social cognition. Integrated Psychological Therapy (IPT) is a promising approach that integrates interventions in neurocognition, social cognition, and functional level. This study examines IPT's efficacy in chronic middle-aged inpatients. Methods: A randomized controlled study involved 44 individuals with schizophrenia. Twenty-one IPT participants received 50 biweekly sessions and medication, while twenty-three control participants received treatment as usual/supportive therapy and pharmacotherapy. Pre- and post-intervention and six- and twelve-month follow-ups were arranged to assess neurocognition, social perception, psychopathology, and functioning using the Matrics Consensus Cognitive Battery, Social Perception Scale, Positive and Negative Syndrome Scale, and Global Assessment of Functioning. Results: Speed of processing, attention/vigilance, overall composite, and neurocognitive composite scores improved significantly in the IPT group. Social Perception Scale performance improved in all areas after the intervention and persisted for 6 months. Positive, negative, and total psychopathology symptoms decreased significantly post-intervention and at the 12-month follow-up, whereas participants' functioning improved significantly. Conclusions: Middle-aged chronic inpatients with schizophrenia may benefit from IPT in neurocognition, social perception, psychopathology, and functioning. This field of study may provide insight into schizophrenia treatment, hence further research is encouraged.

Is KIBRA polymorphism associated with memory performance and cognitive impairment in Alzheimer's disease?

BACKGROUND: Genetic variations in a common single nucleotide polymorphism in the ninth intron of the KIBRA gene have been linked to memory performance and risk of Alzheimer's disease (AD). OBJECTIVE: We examined the risk of AD related to presence of KIBRA T allele (versus CC homozygote) and to memory performance. The role of established genetic risk factors APOE ε4 and BDNF Met was also considered. METHODS: Participants were cognitively healthy individuals (n = 19), participants with amnestic mild cognitive impairment (aMCI) due to AD (n = 99) and AD dementia (n = 37) from the Czech Brain Aging Study. Binary and multinomial logistic regressions compared odds of belonging to a certain diagnostic category and multivariate linear regressions assessed associations with memory. RESULTS: KIBRA T allele was associated with increased AD dementia risk (odds ratio [OR] = 5.98, p = 0.012) compared to KIBRA CC genotype. In APOE ε4 negative individuals, KIBRA T allele was associated with a greater risk of both aMCI due to AD (OR = 6.68, p = 0.038) and AD dementia (OR = 15.75, p = 0.009). In BDNF Met positive individuals, the KIBRA T allele was associated with a greater risk of AD dementia (OR = 10.98, p = 0.050). In AD dementia, the association between KIBRA T allele and better memory performance approached significance (ß = 0.42; p = 0.062). The link between possessing the KIBRA T allele and better memory reached statistical significance only among BDNF Met carriers (ß = 1.21, p = 0.027). CONCLUSIONS: Findings suggest that KIBRA T allele may not fully protect against AD dementia but could potentially delay progression of post-diagnosis cognitive deficits.

Particulate matter induced cognitive impairments via endoplasmic reticulum stress-mediated damage to mitochondria-associated endoplasmic reticulum membranes in immature rats.

Particulate matter (PM) exposure has been increasingly recognized as detrimental to cognitive function and is associated with neurodevelopmental disorders. Mitochondria-associated endoplasmic reticulum membranes (MAMs) form an integrated interface between mitochondria and the endoplasmic reticulum (ER), facilitating crucial cellular functions. Prolonged ER stress (ERS) is implicated in various pathological states in the nervous system. MAMs and ERS may play vital roles in adverse effects of early-life PM exposure on cognitive abilities. This study investigated whether ERS plays a role in PM-induced MAMs dysfunction, leading to neuronal damage and cognitive impairments in early postnatal rats. Using a rat model with PM exposure concentrations of 2 and 10 mg/kg from postnatal Day 3 (PND3) to PND28, we observed that PM exposure resulted in anxiety-like behavior and impaired spatial working memory. The protein levels of ERS markers, including GRP78 and CHOP, were significantly increased in response to PM exposure. Western blot, transmission electron microscopy (TEM), and immunofluorescence analyses revealed decreased MAMs-related proteins and disrupted MAM structure and function caused by PM exposure. Administration of the ERS inhibitor 4-phenylbutyric acid (4-PBA) ameliorated these effects, restoring MAMs integrity and improving cognitive deficits. These findings highlighted the key role of ERS-MAMs dysfunction in PM-induced neurotoxicity and cognitive impairments, providing a new perspective and strategy for the prevention of cognitive deficits in early age with PM exposure.

Association of Insomnia with Functional Outcomes Relevant to Daily Behaviors and Sleep-Related Quality of Life among First Nations People in Two Communities in Saskatchewan, Canada.

Insomnia is a common sleep complaint in Canada and is associated with increased use of health care services and economic burden. This paper examines the association of insomnia with functional outcomes relevant to daily behaviors and sleep-related quality of life among First Nations participants using the Functional Outcomes of Sleep Questionnaire (FOSQ-10). The First Nations Sleep Health Project follow-up survey was conducted in partnership with two Cree First Nations in the summer of 2022, where 355 individuals participated. Statistical analysis was conducted using logistic regression models. The mean age of the participants was 40.76 ± 14.60 (SD) years, and 59.4% were females. The prevalence of chronic insomnia (Insomnia Severity Index score of ≥15) was 21.0%, with more females (26.1%) than males (13.8%) experiencing it among the 348 participants. Overall, the mean FOSQ-10 score was 17.27 ± 2.98 among the 350 participants, with those who had clinical insomnia reporting significantly lower scores than those without clinical insomnia (mean ± SD: 14.6 ± 3.9 vs. 18.0 ± 2.1; p < 0.001). The FOSQ-10 scores indicated sleep-related functional impairment (FOSQ-10 total score < 17.90) in 46.6% of participants. After adjusting for age, excessive daytime sleepiness, sex, and regular use of prescription medication, we found that clinical insomnia was significantly associated with functional impairments. In fact, a person with clinical insomnia was 3.5 times more likely to have functional impairments than those without clinical insomnia. This study highlights the significant association between insomnia and functional impairments related to daily behaviors and quality of life in two First Nation communities. Identifying this association can help healthcare providers to diagnose and treat patients with insomnia in these communities.

Lycopene attenuates D-galactose-induced memory and behavioral deficits by mediating microbiota-SCFAs-gut-brain axis balance in female CD-1 mice.

Aging impairs cognitive function, whereas nutritional intervention can delay aging and age-related diseases. Lycopene (LYC), a naturally occurring carotenoid, posses multiple health-promoting properties, including neuroprotective function. Here, the effects of LYC on memory and behavioral deficits induced by D-galactose (D-gal) treatment and the relative contribution of LYC-derived gut microbiota in these process were investigated. Results demonstrated that LYC showed effective protection on D-gal induced cognitive deficit and neuronal damage. Moreover, LYC treatment has beneficial effects on gut barrier damage, microbiota dysbiosis and levels of SCFAs in D-gal-induced subacute aging mice. Next, fecal microbiota transplantation (FMT) experiment was performed and increased SCFAs were observed in mice received stools from D-gal+LYC group when compared with D-gal-FMT group. Thus, we added SCFAs treatment served as a control group in order to evaluated whether the alterations of gut-brain axis could be attributed to LYC-reshaped gut microbiota and SCFAs. Results showed that recipient mice received SCFAs and stools from D-gal+LYC group have similar beneficial effects in improving gut and brain function, demonstrated as: improved intestinal health via elevating antioxidant enzymes contents, increasing the expressions of tight junctions proteins and protecting gut barrier, enhanced mice working memory capacity via alleviating hippocampal neurons impairment, improving synaptic function and enhancing mitochondrial function in the intestinal pseudo-aseptic mice. In conclusion, our results demonstrated that LYC-derived microbiome played a pivotal role in the regulation of cognitive functions during aging and enhanced SCFAs formation might be an important signaling molecule connecting gut microbiome and brain.

Prevalence of multiple long-term chronic conditions and associated disabilities among community-dwelling adults in Riyadh.

Background/objectives: Saudi Arabia is experiencing a rapid increase in chronic diseases and disabilities. However, there is a dearth of research on these topics in the Arab world. This study aimed to examine the prevalence of multiple long-term chronic conditions (MLTCs) and disabilities and their relationship. Methods: The survey was conducted in Riyadh, Saudi Arabia, in 2023. Convenient sampling was used to select 324 participants aged 50 years and older, using data on disabilities status. The survey collected information on age, sex, body mass index (BMI), MLTCs or multi-morbidity, and activities of daily living (ADL). Disabilities was measured using Arabic versions of basic ADL and the Barthel index. Results: The prevalence of MLTCs among participants was 49.4%. The prevalence of disabilities measured using the ADL and Barthel index was 33.6 and 49.7%, respectively, and these rates increased by 42.5 and 58.1% among participants with MLTCs (n = 160). MLTCs were associated with an increased risk of disabilities using ADL [odds ratio (OR) 1.99, p = 0.037] and the Barthel index (OR 2.27, p = 0.007). Conclusion: Approximately half of the participants with disabilities data had MLTCs, and approximately a third to half had a disabilities. MLTCs were significantly associated with various types of disabilities among community-dwelling Saudi adults. Hence, strategies to reduce chronic diseases may result in a reduction in disabilities, and vice versa.

Behaviour and Psychopathology in Preschool Children with William Syndrome and the Effects of Age, Sex and Cognition.

The current study compared the prevalence of cognitive and psychopathological impairments among 24 preschool children with Williams syndrome (WS) (aged 2.20 to 5.97 years) and 53 controls without WS and screened for developmental or psychological diagnoses (aged 2.21 to 5.89 years) matched on chronological age and sex distribution. Associations between sex, chronological age, early development and psychopathology were also investigated. The Child Behavior Checklist-Preschool Version (CBCL) and the Mullen Scales of Early Learning were administered. Higher reported rates of Attention Problems, Emotional Reactivity, Somatic Complaints, Withdrawal, Affective Problems and Total Problems were found in preschool children with WS. There were no significant group differences in prevalence rates of all other CBCL domains. Attention Problems were the most prevalent psychopathology in preschool children with WS (33% falling in the clinically significant range), followed by Affective Problems (29% in clinically significant range), then Anxiety Problems (17%) or Attention Deficit/Hyperactivity Problems (17%). Among children without WS, the highest prevalence rates of psychopathology were for Attention Problems (4% falling in the clinically significant range), Aggressive Behaviour (4%), Sleep Problems (4%) and Oppositional Defiant Problems (4%). There were no significant associations between sex or chronological age and CBCL-reported psychopathology for either group. In addition, there were no significant relationships between CBCL ratings and verbal ability, nonverbal ability or overall developmental level in either group. Findings highlight variations in the pattern of psychopathology among preschool children with WS compared to those without WS, which needs to be considered in clinical management and future research.

Neuromuscular impairments of cerebral palsy: contributions to gait abnormalities and implications for treatment.

Identification of neuromuscular impairments in cerebral palsy (CP) is essential to providing effective treatment. However, clinical recognition of neuromuscular impairments in CP and their contribution to gait abnormalities is limited, resulting in suboptimal treatment outcomes. While CP is the most common childhood movement disorder, clinical evaluations often do not accurately identify and delineate the primary neuromuscular and secondary musculoskeletal impairments or their specific impact on mobility. Here we discuss the primary neuromuscular impairments of CP that arise from early brain injury and the progressive secondary musculoskeletal impairments, with a focus on spastic CP, the most common form of CP. Spastic CP is characterized by four primary interrelated neuromuscular impairments: 1. muscle weakness, 2. short muscle-tendon units due to slow muscle growth relative to skeletal growth, 3. muscle spasticity characterized by increased sensitivity to stretch, and 4. impaired selective motor control including flexor and extensor muscle synergies. Specific gait events are affected by the four primary neuromuscular impairments of spastic CP and their delineation can improve evaluation to guide targeted treatment, prevent deformities and improve mobility. Emerging information on neural correlates of neuromuscular impairments in CP provides the clinician with a more complete context with which to evaluate and develop effective treatment plans. Specifically, addressing the primary neuromuscular impairments and reducing secondary musculoskeletal impairments are important treatment goals. This perspective on neuromuscular mechanisms underlying gait abnormalities in spastic CP aims to inform clinical evaluation of CP, focus treatment more strategically, and guide research priorities to provide targeted treatments for CP.

Distinct Longitudinal Changes in EEG Measures Reflecting Functional Network Disruption in ALS Cognitive Phenotypes.

Amyotrophic lateral sclerosis (ALS) is characterised primarily by motor system degeneration, with clinical evidence of cognitive and behavioural change in up to 50% of cases. We have shown previously that resting-state EEG captures dysfunction in motor and cognitive networks in ALS. However, the longitudinal development of these dysfunctional patterns, especially in networks linked with cognitive-behavioural functions, remains unclear. Longitudinal studies on non-motor changes in ALS are essential to further develop our understanding of disease progression, improve care and enhance the evaluation of new treatments. To address this gap, we examined 124 ALS individuals with 128-channel resting-state EEG recordings, categorised by cognitive impairment (ALSci, n = 25), behavioural impairment (ALSbi, n = 58), or non-impaired (ALSncbi, n = 53), with 12 participants meeting the criteria for both ALSci and ALSbi. Using linear mixed-effects models, we characterised the general and phenotype-specific longitudinal changes in brain network, and their association with cognitive performance, behaviour changes, fine motor symptoms, and survival. Our findings revealed a significant decline in [Formula: see text]-band spectral power over time in the temporal region along with increased [Formula: see text]-band power in the fronto-temporal region in the ALS group. ALSncbi participants showed widespread ß-band synchrony decrease, while ALSci participants exhibited increased co-modulation correlated with verbal fluency decline. Longitudinal network-level changes were specific of ALS subgroups and correlated with motor, cognitive, and behavioural decline, as well as with survival. Spectral EEG measures can longitudinally track abnormal network patterns, serving as a candidate stratification tool for clinical trials and personalised treatments in ALS.

EPO Deficiency Upregulates GADD45b/p38 MAPK Axis, Mediating Schizophrenia-Related Synaptic and Cognitive Impairments.

Schizophrenia (SZ) is a chronic and severe mental illness associated with psychiatric symptoms, cognitive deficits, and social dysfunction. Current clinical interventions only limit relief of psychiatric symptoms and have minimal impact on cognitive impairments. Erythropoietin (EPO), known for its role in neurogenesis and synaptic plasticity, is significantly low in SZ patients. However, the role of EPO deficiency in SZ-associated cognitive deficits remains unclear. In this study, we used the MK801-induced SZ rat model to show that EPO levels were significantly decreased, correlating with cognitive impairments. EPO supplementation mitigated apoptosis, synaptic damage, and cognitive impairments caused by MK801. RNA-sequencing and Western blot analysis revealed increased expression of growth arrest and DNA damage 45b (GADD45b) in MK801-treated rats, reversed by EPO supplementation. Moreover, overexpression of GADD45b exacerbated neuronal loss and cognitive impairments in male Sprague-Dawley rats, while downregulation of GADD45b rescued these SZ-related pathologies. Notably, the benefits of EPO supplementation on SZ pathology were blocked by GADD45b overexpression. Inhibition of p38 MAPK, a GADD45b target, reduced MK801-induced apoptosis and synaptic damage. These findings uncover a novel etiopathogenic mechanism of SZ-related cognitive impairments, driven by EPO deficiency and the activation of the GADD45b/p38 MAPK axis.

Spatiotemporal variation in fish mercury contamination: Comparing approaches for crafting consumption advisories and assessing impairment.

Mercury in fish is a serious human health concern. Mercury is a widespread contaminant that exceeds health effect thresholds in many fish species and waterbodies. The objectives were to determine the spatiotemporal variation of mercury in fish tissue for several fish species across thousands of lakes and to assess the potential use of fish length standardization and statistical models to improve fish consumption guidelines and impairments determinations in lake-rich areas. The results showed that fish length, species, ecoregion, lake size, latitude, color dissolved organic matter, water clarity, and zebra mussel presence influenced mercury concentrations. Fish mercury concentrations were generally higher from 1967 to 1990, and since 1990 there was no obvious trend. We found that a statistical model provided estimates of mean mercury concentrations by fish total length that were unbiased and with greater confidence than those based solely on sample statistics. The use of fish length standardization and inclusion of predictive models could improve precision and consistency of fish consumption guidelines and impairments determinations.

The collaborative cross mouse for studying the effect of host genetic background on memory impairments due to obesity and diabetes.

BACKGROUND: Over the past few decades, a threefold increase in obesity and type 2 diabetes (T2D) has placed a heavy burden on the health-care system and society. Previous studies have shown correlations between obesity, T2D, and neurodegenerative diseases, including dementia. It is imperative to further understand the relationship between obesity, T2D, and cognitive deficits. METHODS: This investigation tested and evaluated the cognitive impact of obesity and T2D induced by high-fat diet (HFD) and the effect of the host genetic background on the severity of cognitive decline caused by obesity and T2D in collaborative cross (CC) mice. The CC mice are a genetically diverse panel derived from eight inbred strains. RESULTS: Our findings demonstrated significant variations in the recorded phenotypes across different CC lines compared to the reference mouse line, C57BL/6J. CC037 line exhibited a substantial increase in body weight on HFD, whereas line CC005 exhibited differing responses based on sex. Glucose tolerance tests revealed significant variations, with some lines like CC005 showing a marked increase in area under the curve (AUC) values on HFD. Organ weights, including brain, spleen, liver, and kidney, varied significantly among the lines and sexes in response to HFD. Behavioral tests using the Morris water maze indicated that cognitive performance was differentially affected by diet and genetic background. CONCLUSIONS: Our study establishes a foundation for future quantitative trait loci mapping using CC lines and identifying genes underlying the comorbidity of Alzheimer's disease (AD), caused by obesity and T2D. The genetic components may offer new tools for early prediction and prevention.

Enhancing navigation and obstacle avoidance with a vibrotactile device as secondary electronic travel aid.

People with visual impairments commonly rely on the use of a white cane to navigate and avoid obstacles. Although this analog tool is highly reliable and easy to use, its drawback is the impossibility to anticipate obstacles beyond reach and routes, as well as obstacles above waist level. Electronic travel aids (ETAs) and sensory substitution devices (SSDs) are new technological solutions designed to enhance the tactile and/or auditory capabilities to access the information needed to overcome those drawbacks. In the present study, 25 individuals with visual impairments used the T-Sight, a vibrotactile SSD, and/or the white cane in a navigation task involving obstacle avoidance. While the performance achieved with the device, measured by the number of collisions and walking speed, did not surpass the white cane, the SSD did have a positive impact on ambulation. Participants reduced the number of white cane touches towards environmental obstacles and performed obstacle avoidance maneuvers earlier. These results demonstrate the potential of vibrotactile devices to address the limitations of the white cane.

Assessments of secondary travel aids for people with visual impairments should include performance measures beyond speed and number of collisions.These include the number of alerts, white cane touches, and trajectory analysis.Our vibrotactile secondary ETA allows improvements in navigation and obstacle avoidance shown as a reduction in the use of the white cane and an anticipation of the avoidance maneuvers.

Bibliometric Analysis of Research on Exercise Intervention for Cancer-Related Cognitive Impairments.

Introduction: Cancer treatments frequently lead to cognitive impairments, affecting a substantial global population. Among various approaches, exercise has emerged as a promising strategy for rehabilitation. However, a comprehensive bibliometric analysis of research in this field is lacking. Methods: We conducted a bibliometric analysis of 10,345 articles sourced from the Web of Science database using the R package "bibliometrix". Our analysis examined publication trends, leading countries, journals, authors, institutions, keywords, and prevalent themes. Results: Over the past two decades, research on exercise interventions for cancer-related cognitive impairments (CRCI) has advanced significantly. Nonetheless, challenges persist in elucidating underlying mechanisms, developing innovative strategies, and creating effective tools. Conclusions: The number of publications notably increased from 1998 to 2023, although there has been a recent decline in citations. The United States (US) leads in both publications and citations, while China is showing increasing influence. Using Lotka's Law in our bibliometric analysis, we identified 58 key authors in the field of exercise interventions for CRCI. Leading institutions such as the University of Toronto and Duke University are at the forefront of this research. Although the Journal of Clinical Oncology has fewer publications, it remains influential. Current research focuses on exercise interventions to enhance the quality of life for cancer patients, with particular emphasis on cognitive rehabilitation in breast cancer and the challenges faced by survivors. Future research should delve deeper into intervention mechanisms, behavioral strategies, telemedicine, and precise cognitive assessment tools.

Intraspinal microstimulation of the ventral horn has therapeutically relevant cross-modal effects on nociception.

Electrical stimulation of spinal networks below a spinal cord injury is a promising approach to restore functions compromised by inadequate and/or inappropriate neural drive. The most translationally successful examples are paradigms intended to increase neural transmission in weakened yet spared descending motor pathways and spinal motoneurons rendered dormant after being severed from their inputs by lesion. Less well understood is whether spinal stimulation is also capable of reducing neural transmission in pathways made pathologically overactive by spinal cord injury. Debilitating spasms, spasticity and neuropathic pain are all common manifestations of hyperexcitable spinal responses to sensory feedback. Whereas spasms and spasticity can often be managed pharmacologically, spinal cord injury-related neuropathic pain is notoriously medically refractory. Interestingly, however, spinal stimulation is a clinically available option for ameliorating neuropathic pain arising from aetiologies other than spinal cord injury, and the limited evidence available to date suggests that it holds considerable promise for reducing spinal cord injury-related neuropathic pain, as well. Spinal stimulation for pain amelioration has traditionally been assumed to modulate sensorimotor networks overlapping with those engaged by spinal stimulation for rehabilitation of movement impairments. Thus, we hypothesize that spinal stimulation intended to increase the ability to move voluntarily may simultaneously reduce transmission in spinal pain pathways. To test this hypothesis, we coupled a rat model of incomplete thoracic spinal cord injury, which results in moderate to severe bilateral movement impairments and spinal cord injury-related neuropathic pain, with in vivo electrophysiological measures of neural transmission in networks of spinal neurons integral to the development and persistence of the neuropathic pain state. We find that when intraspinal microstimulation is delivered to the ventral horn with the intent of enhancing voluntary movement, transmission through nociceptive specific and wide dynamic range neurons is significantly depressed in response to pain-related sensory feedback. By comparison, spinal responsiveness to non-pain-related sensory feedback is largely preserved. These results suggest that spinal stimulation paradigms could be intentionally designed to afford multi-modal therapeutic benefits, directly addressing the diverse, intersectional rehabilitation goals of people living with spinal cord injury.

Exploring the Therapeutic Potential of Green Tea (Camellia sinensis L.) in Anti-Aging: A Comprehensive Review of Mechanisms and Findings.

Green tea (GT) is rich in Phyto-active compounds such as epigallocatechin gallate (EGCG), epigallocatechin (EGC), epicatechin gallate (ECG), epicatechin (EC), catechin, and tannic acid, which exhibit synergistic effects when combined. Preclinical studies demonstrate that GT and its compounds can reduce reactive oxygen species (ROS), enhance antioxidant capacity, and alleviate aging-related issues such as memory impairments, cognitive decline, and shortened lifespan. Clinical trials corroborate the efficacy of topical GT formulations in improving skin tone, texture, and elasticity and reducing wrinkles. The present manuscript summarizes the recent update on the anti-aging potential of GT and its possible mechanisms. The literature survey suggested that GT consumption is linked to improved cognition, reduced depression levels, and activation of pathways in model organisms like C. elegans. Additionally, tea polyphenols enhance fibroblast mitophagy, boost hippocampal synaptic plasticity in rodents, and mitigate age-related cognitive decline. Moreover, EGCG exhibits anti-aging properties by reducing TNF-induced MMP-1 expression, suppressing ERK signaling, and inhibiting MEK and Src phosphorylation in human dermal fibroblasts. In the context of skin permeation and deposition, optimized transpersonal formulation (TF) incorporating EGCG and hyaluronic acid (HA) demonstrated significantly increased skin permeation and deposition of EGCG compared to plain EGCG. Furthermore, EGCG protects cardiomyocytes via the PPARγ pathway and combats age-related muscle loss through miRNA-486-5p regulation, AKT activation, and FoxO1a-mediated expression of MuRF1 and Atrogin-1. In conclusion, the regular consumption of GT holds promise for promoting physical and mental health, delaying brain and skin aging, and improving overall health by enhancing total antioxidant capacity.

Effects of Boron on Learning and Behavioral Disorders in Rat Autism Model Induced by Intracerebroventricular Propionic Acid.

Autism spectrum disorder is a neurodevelopmental disorder in which learning, communication, and social interaction are impaired. Research has sought to minimize the neural impairments associated with autism spectrum disorder and improve the quality of life. Recent studies suggest that boron may benefit nerve cells, with effects varying depending on the dosage. This study explored the impact of boron, administered as boric acid, on behavioral, biochemical, and histopathological parameters in a rat model of autism induced by propionic acid (PPA). Thirty-two male Sprague-Dawley rats were divided into control, autism model, and boron-treated groups. Behavioral tests were conducted pre- and post-PPA induction, with brain tissue analyzed post-euthanasia. Proinflammatory cytokines (tumor necrosis factor alpha (TNF-α), interleukin 1 beta (IL-1ß), interleukin 6 (IL-6)) and brain-derived neurotrophic factor (BDNF) levels were assessed in the hippocampus. Histopathological evaluations were conducted on the hippocampus and cerebellum. Autism model rats displayed impaired learning, elevated BDNF and cytokine levels, microglial and astrocytic activation, and decreased Purkinje cell count. The boron-treated groups showed improvements, particularly with the 4 mg/kg dose. This dose enhanced learning and social interaction, reduced proinflammatory cytokine levels, prevented microglial and astrocytic activation, and increased Purkinje cell count. Boron treatment exhibited neuroprotective potential, ameliorating autism spectrum disorder deficits by modulating cytokines, BDNF, microglia, and astrocytes, with low doses yielding pronounced effects.

Early elevations in arterial pressure: a contributor to rapid depressive symptom emergence in female Zucker rats with metabolic disease?

One of the growing challenges to public health and clinical outcomes is the emergence of cognitive impairments, particularly depressive symptom severity, because of chronic elevations in metabolic disease and cerebrovascular disease risk. To more clearly delineate these relationships and to assess the potential for sexual dimorphism, we used lean (LZR) and obese Zucker rats (OZR) of increasing age to determine relationships between internal carotid artery (ICA) hemodynamics, cerebral vasculopathies, and the emergence of depressive symptoms. Male OZR exhibited progressive elevations in perfusion pressure within the ICA, which were paralleled by endothelial dysfunction, increased cerebral arterial myogenic activation, and reduced cerebral cortex microvessel density. In contrast, female OZR exhibited a greater degree of ICA hypertension than male OZR but maintained normal endothelial function, myogenic activation, and microvessel density to an older age range than did males. Although both male and female OZR exhibited significant and progressive elevations in depressive symptom severity, these were significantly worse in females. Finally, plasma cortisol concentration was elevated higher and at a younger age in female OZR as compared with males, and this difference was maintained to final animal usage at ∼17 wk of age. These results suggest that an increased severity of blood pressure waves may penetrate the cerebral circulation more deeply in female OZR than in males, which may predispose the females to a more severe emergence of depressive symptoms with chronic metabolic disease, whereas males may be more predisposed to more direct cerebral vasculopathies (e.g., stroke, transient ischemic attack).NEW & NOTEWORTHY We provide novel insight that the superior maintenance of cerebrovascular endothelial function in female versus male rats with chronic metabolic disease buffers myogenic activation of cerebral resistance arteries/arterioles despite worsening hypertension. As hypertension development is earlier and more severe in females, potentially due to an elevated stress response, the blunted myogenic activation allows greater arterial pressure wave penetrance into the cerebral microcirculation and is associated with accelerated emergence/severity of depressive symptoms in obese female rats.

Cognitive impairments and neurobiological changes induced by unilateral vestibular dysfunction in mice.

The vestibular system is essential for balance and spatial orientation, and its dysfunction can lead to cognitive deficits. This study investigates the effects of unilateral vestibular dysfunction (UVL) on cognitive function and the underlying neurobiological changes in mice. We established a unilateral labyrinthectomy (UL) model in mice and assessed cognitive function at 28 days post-surgery using a comprehensive battery of behavioral tests. We found significant impairments in spatial reference memory, working memory, and synaptic plasticity in UL mice, which persisted despite compensation for vestibular and postural motor deficits. Immunofluorescence staining revealed enhanced activation of c-Fos in the hippocampal dentate gyrus (DG) at various time points post-UL, suggesting a role of the hippocampus in cognitive deficits following UVL. RNA sequencing of the DG identified differentially expressed genes (DEGs) and altered pathways related to cognitive function, synaptic plasticity, and neuronal activation. Quantitative real-time PCR (qRT-PCR) validated the expression changes of selected genes. Our findings indicate that UVL leads to persistent cognitive impairments in mice, associated with altered neuronal activation and gene expression in the hippocampus. This study offers valuable insights into the neurobiological mechanisms underlying cognitive deficits associated with UVL. Moreover, it underscores the importance of early cognitive screening in patients with vestibular diseases, as this approach is instrumental in comprehensive condition assessment, precise diagnosis, targeted treatment, and effective rehabilitation.

From antidepressants and psychotherapy to oxytocin, vagus nerve stimulation, ketamine and psychedelics: how established and novel treatments can improve social functioning in major depression.

Social cognitive deficits and social behavior impairments are common in major depressive disorder (MDD) and affect the quality of life and recovery of patients. This review summarizes the impact of standard and novel treatments on social functioning in MDD and highlights the potential of combining different approaches to enhance their effectiveness. Standard treatments, such as antidepressants, psychotherapies, and brain stimulation, have shown mixed results in improving social functioning, with some limitations and side effects. Newer treatments, such as intranasal oxytocin, mindfulness-based cognitive therapy, and psychedelic-assisted psychotherapy, have demonstrated positive effects on social cognition and behavior by modulating self-referential processing, empathy, and emotion regulation and through enhancement of neuroplasticity. Animal models have provided insights into the neurobiological mechanisms underlying these treatments, such as the role of neuroplasticity. Future research should explore the synergistic effects of combining different treatments and investigate the long-term outcomes and individual differences in response to these promising interventions.