Publications by authors named "Viktoriya Nikolova"

Background: We previously reported greater reductions in depression and anxiety following probiotic supplementation in people with major depressive disorder (MDD) in a randomised double-blind placebo-controlled pilot trial (Nikolova et al., 2023). Here, we investigate the mechanisms underlying these effects.

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Perineuronal nets (PNNs) are a specialized extracellular matrix that surrounds certain populations of neurons, including (inhibitory) parvalbumin (PV)-expressing interneurons throughout the brain and (excitatory) CA2 pyramidal neurons in hippocampus. PNNs are thought to regulate synaptic plasticity by stabilizing synapses and as such, could regulate learning and memory. Most often, PNN functions are queried using enzymatic degradation with chondroitinase, but that approach does not differentiate PNNs on CA2 neurons from those on adjacent PV cells.

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Perineuronal nets (PNNs) are a specialized extracellular matrix that surround certain populations of neurons, including (inhibitory) parvalbumin (PV) expressing-interneurons throughout the brain and (excitatory) CA2 pyramidal neurons in hippocampus. PNNs are thought to regulate synaptic plasticity by stabilizing synapses and as such, could regulate learning and memory. Most often, PNN functions are queried using enzymatic degradation with chondroitinase, but that approach does not differentiate PNNs on CA2 neurons from those on adjacent PV cells.

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Article Synopsis
  • Researchers explored the connection between heavy alcohol use and obesity as midlife risk factors for late-onset Alzheimer's disease (LOAD), uncovering a link to disrupted lipophagy and lysosomal function.
  • The study found that the loss of lysosomal acid lipase (LAL) in neurons leads to the accumulation of neuronal lysosomal lipids (NLL), which interferes with the clearance of amyloid-beta (Aβ), a key component of Alzheimer's pathology.
  • As LAL levels decline with age in both mice and humans, its reduction is associated with increased Aβ and cognitive deficits, highlighting the importance of maintaining LAL function to potentially mitigate Alzheimer's risk as we age.
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  • Autism Spectrum Disorder (ASD) is primarily seen in males and is marked by difficulties in communication and social behaviors, which this study examined using a mouse model.* -
  • The research utilized various sequencing techniques to discover differences in gene expression and methylation patterns in the amygdala of two mouse strains, revealing potential links to sociability deficits.* -
  • Results indicated that altered immune-related processes and oligodendrocyte/microglia differentiation were associated with ASD traits, highlighting the need for further research into these mechanisms and the effects of oxytocin.*
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  • Sleep disruption and Tau accumulation are linked to cognitive decline in Alzheimer's disease, but the relationship between them is not fully understood.
  • In a study using PS19 mice, early-onset hyperarousal and selective sleep disruption were observed, with significant memory decline due to chronic sleep disruption occurring in males.
  • Despite earlier hyperarousal in females, they showed more resilience in cognitive decline compared to males, indicating potential sex-specific differences in the effects of sleep disruption on cognitive health.
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  • Autism Spectrum Disorder (ASD) is linked to communication and social behavior challenges, with this study exploring the underlying brain mechanisms and sex differences in ASD using mouse models.
  • Research involved measuring sociability in mice, analyzing gene expression changes, and identifying differentially methylated genes related to immune processes in the amygdala.
  • Results showed significant differences in social behavior and brain activity between mouse strains, including impaired myelination linked to ASD, with potential therapeutic insights regarding oxytocin, but further studies are needed to clarify these cellular mechanisms.
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  • TDP-43 proteinopathies, such as frontotemporal lobar degeneration (FTLD) and amyotrophic lateral sclerosis (ALS), are neurodegenerative diseases where the protein TDP-43 misfolds and disrupts neuronal function.
  • Researchers created models that mimic sporadic TDP-43 proteinopathy, showing how acetylation at lysine 145 impairs TDP-43's ability to bind RNA and leads to gene mis-regulation.
  • Results indicate that this acetylation triggers harmful changes in neurons, evidenced by cognitive decline and altered gene expression related to synaptic function, mirroring characteristics seen in human FTLD cases.
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  • Sleep disruption is linked to neurodegenerative diseases like Alzheimer's, where impaired synaptic processes may contribute to cognitive decline, particularly through Tau protein aggregation.
  • A study using transgenic mice revealed that PS19 mice experience early loss of sleep during the dark phase, with females showing symptoms earlier than males.
  • Although sleep disruption did not increase Tau pathology in the brain, chronic sleep loss was found to worsen spatial memory decline specifically in male mice.
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Importance: The microbiota-gut-brain axis is a promising target for novel treatments for mood disorders, such as probiotics. However, few clinical trials have been conducted, and further safety and efficacy data are needed to support this treatment approach.

Objective: To provide acceptability and tolerability data and estimates of intervention effect size for probiotics as adjunctive treatment for patients with major depressive disorder (MDD).

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Purpose: Treatment-resistant depression (TRD) is associated with profound morbidity for patients, placing a significant burden on those affected, the health service and wider society. Despite this, TRD remains chronically underserved in terms of viable treatment options. To address this gap, an advisory panel of psychiatrists and clinical researchers with experience in managing TRD convened to develop best practice statements on the use of esketamine nasal spray, one of the first TRD treatments to be licensed in 30 years.

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  • Behavioral phenotyping in neonatal mice helps researchers study how early changes in brain development relate to human neurodevelopmental disorders.
  • This chapter outlines a testing method that assesses mice behavior while reducing stress for the pups and their mothers.
  • Testing starts when mice are 6-8 days old and includes various evaluations up to 20-21 days, focusing on different behavioral traits like movement and reflexes.
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  • Patients with autism spectrum disorder (ASD) experience significant sleep disruptions early in life, which may have lasting developmental effects; researchers investigated this in mice with a SHANK3 gene mutation linked to ASD.
  • They recorded sleep patterns in Shank3 mutated mice and wild-type siblings, exposing them to early life sleep disruption and comparing various behavioral outcomes later in adulthood.
  • Results showed that Shank3 mice slept less and exhibited distinct behavioral changes based on sex and early life sleep disruption, whereas wild-type mice appeared resilient, highlighting potential long-term consequences of sleep issues in genetically vulnerable populations.
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  • Heavy alcohol use in adolescence is linked to an increased risk of Alzheimer's disease (AD), but the specific mechanisms connecting the two remain unclear.
  • A study using a mouse model showed that binge drinking during adolescence led to heightened levels of toxins associated with AD and increased inflammation in the brain, particularly in females.
  • Treatment with the anti-inflammatory drug minocycline during the binge drinking period mitigated some of the harmful effects, including increased anxiety and memory loss, suggesting that inflammation plays a critical role in these changes.
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Objective: The increased prevalence and incidence of affective disorders among patients with gastrointestinal disease have been well established. However, few studies have investigated the inverse relationship. We aimed to identify all pieces of evidence of the prevalence and incidence of irritable bowel syndrome (IBS) and inflammatory bowel disease (IBD) in people with depression and bipolar disorder.

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Neurologic disorders often disproportionately affect specific brain regions, and different apoptotic mechanisms may contribute to white matter pathology in leukodystrophies or gray matter pathology in poliodystrophies. We previously showed that neural progenitors that generate cerebellar gray matter depend on the anti-apoptotic protein BCL-xL. Conditional deletion of Bcl-xL in these progenitors produces spontaneous apoptosis and cerebellar hypoplasia, while similar conditional deletion of Mcl-1 produces no phenotype.

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Importance: Evidence of gut microbiota perturbations has accumulated for multiple psychiatric disorders, with microbiota signatures proposed as potential biomarkers. However, no attempts have been made to evaluate the specificity of these across the range of psychiatric conditions.

Objective: To conduct an umbrella and updated meta-analysis of gut microbiota alterations in general adult psychiatric populations and perform a within- and between-diagnostic comparison.

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Recent years have seen a rapid increase in the use of gut microbiota-targeting interventions, such as probiotics, for the treatment of psychiatric disorders. The objective of this update review was to evaluate all randomised controlled clinical trial evidence on the efficacy of probiotics for clinical depression. Cochrane guidelines for updated reviews were followed.

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The dentate gyrus (DG) is a unique brain structure in that neurons can be generated postnatally and integrated within existing circuitry throughout life. The maturation process of these newly generated neurons (granule cells) is modulated by nicotinic acetylcholine receptors (nAChRs) through a variety of mechanisms such as neural stem pool proliferation, cell survival, signal modulation, and dendritic integration. Disrupted nAChR signaling has been implicated in neuropsychiatric and neurodegenerative disorders, potentially via alterations in DG neurogenesis.

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Most interventions for treatment-resistant depression (TRD) are added as augmenters. We aimed to determine the relative effectiveness of augmentation treatments for TRD. This systematic review and network meta-analysis (NMA) sought all randomized trials of pharmacological and psychological augmentation interventions for adults meeting the most common clinical criteria for TRD.

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Angelman syndrome (AS) is a neurodevelopmental disorder characterized by intellectual disability, lack of speech, ataxia, EEG abnormalities, and epilepsy. Seizures in individuals with AS are common, debilitating, and often drug resistant. Thus, there is an unmet need for better treatment options.

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Background: Recently the gut microbiota has attracted significant interest in psychiatric research due to the observed bidirectional gut-brain communication. A growing body of evidence from preclinical work has suggested that probiotics may be effective in reducing stress and anxiety and alleviating low mood. It is unclear to what extent these effects are seen in clinical populations.

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Background: Depression is considered to have the highest disability burden of all conditions. Although treatment-resistant depression (TRD) is a key contributor to that burden, there is little understanding of the best treatment approaches for it and specifically the effectiveness of available augmentation approaches.AimsWe conducted a systematic review and meta-analysis to search and quantify the evidence of psychological and pharmacological augmentation interventions for TRD.

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Currently, there are no established pharmaceutical strategies that effectively treat social deficits in autism spectrum disorder (ASD). Oxytocin, a neurohormone that plays a role in multiple types of social behaviors, has been proposed as a possible therapeutic against social impairment and other symptoms in ASD. However, from the standpoint of pharmacotherapy, oxytocin has several liabilities as a standard clinical treatment, including rapid metabolism, low brain penetrance, and activity at the vasopressin (antidiuretic hormone) receptors.

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