A change in taste: The role of MicroRNAs in altering hedonic value

The mechanisms associated with neophobia, and anhedonia remain largely unknown. Neuropsychological disorders such as depression and schizophrenia are associated with excessive fear and anhedonia and have been linked to microRNA 137. We hypothesized that microRNAs (miRNAs) in the snail Lymnaea stagnalis are important for regulating feeding behaviour through either preventing neophobia or establishing hedonic value. To test these hypotheses, we used an injection of Poly-L-Lysine (PLL) to inhibit miRNA biogenesis and observed its effects on feeding behaviour. We repeated these experiments with pre-exposure to novel stimuli capable of eliciting neophobia to disentangle the processes predicted to regulate feeding behaviour. Next, we exposed snails to food stimuli of high hedonic value after PLL injection to reset their hedonic value for that food. Finally, we consolidated our results with previous research by examining the effect of PLL injection on a one trial appetitive classical conditioning procedure (1TT) to induce long term memory (LTM). We found that miRNAs are likely not required for preventing neophobia. Moreover, we discovered that snails experienced anhedonia in response to inhibition of miRNA biogenesis, resulting in diminished feeding behaviour for food stimuli with a previously high hedonic value. Snails showed diminished feeding behaviour for multiple food stimuli of high hedonic value post 1TT with PLL injection. This finding suggested that PLL causes anhedonia rather than an impairment of LTM formation following the 1TT procedure. This is the first evidence suggesting that inhibiting the biogenesis of miRNAs contributes to anhedonia in Lymnaea.

Allicin, an Antioxidant and Neuroprotective Agent, Ameliorates Cognitive Impairment

Allicin (diallylthiosulfinate) is a defense molecule produced by cellular contents of garlic (Allium sativum L.). On tissue damage, the non-proteinogenic amino acid alliin (S-allylcysteine sulfoxide) is converted to allicin in an enzyme-mediated process catalysed by alliinase. Allicin is hydrophobic in nature, can efficiently cross the cellular membranes and behaves as a reactive sulfur species (RSS) inside the cells. It is physiologically active molecule with the ability to oxidise the thiol groups of glutathione and between cysteine residues in proteins. Allicin has shown anticancer, antimicrobial, antioxidant properties and also serves as an efficient therapeutic agent against cardiovascular diseases. In this context, the present review describes allicin as an antioxidant, and neuroprotective molecule that can ameliorate the cognitive abilities in case of neurodegenerative and neuropsychological disorders. As an antioxidant, allicin fights the reactive oxygen species (ROS) by downregulation of NOX (NADPH oxidizing) enzymes, it can directly interact to reduce the cellular levels of different types of ROS produced by a variety of peroxidases. Most of the neuroprotective actions of allicin are mediated via redox-dependent pathways. Allicin inhibits neuroinflammation by suppressing the ROS production, inhibition of TLR4/MyD88/NF-κB, P38 and JNK pathways. As an inhibitor of cholinesterase and (AChE) and butyrylcholinesterase (BuChE) it can be applied to manage the Alzheimer’s disease, helps to maintain the balance of neurotransmitters in case of autism spectrum disorder (ASD) and attention deficit hyperactive syndrome (ADHD). In case of acute traumatic spinal cord injury (SCI) allicin protects neuron damage by regulating inflammation, apoptosis and promoting the expression levels of Nrf2 (nuclear factor erythroid 2-related factor 2). Metal induced neurodegeneration can also be attenuated and cognitive abilities of patients suffering from neurological diseases can be ameliorates by allicin administration.

AUTS2 Gene: Keys to Understanding the Pathogenesis of Neurodevelopmental Disorders

Neurodevelopmental disorders (NDDs), including autism spectrum disorders (ASD) and intellectual disability (ID), are a large group of neuropsychiatric illnesses that occur during early brain development, resulting in a broad spectrum of syndromes affecting cognition, sociability, and sensory and motor functions. Despite progress in the discovery of various genetic risk factors thanks to the development of novel genomics technologies, the precise pathological mechanisms underlying the onset of NDDs remain elusive owing to the profound genetic and phenotypic heterogeneity of these conditions. Autism susceptibility candidate 2 (AUTS2) has emerged as a crucial gene associated with a wide range of neuropsychological disorders, such as ASD, ID, schizophrenia, and epilepsy. AUTS2 has been shown to be involved in multiple neurodevelopmental processes; in cell nuclei, it acts as a key transcriptional regulator in neurodevelopment, whereas in the cytoplasm, it participates in cerebral corticogenesis, including neuronal migration and neuritogenesis, through the control of cytoskeletal rearrangements. Postnatally, AUTS2 regulates the number of excitatory synapses to maintain the balance between excitation and inhibition in neural circuits. In this review, we summarize the knowledge regarding AUTS2, including its molecular and cellular functions in neurodevelopment, its genetics, and its role in behaviors.

Ionizing Radiation-Induced Brain Cell Aging and the Potential Underlying Molecular Mechanisms

Population aging is occurring rapidly worldwide, challenging the global economy and healthcare services. Brain aging is a significant contributor to various age-related neurological and neuropsychological disorders, including Alzheimer’s disease and Parkinson’s disease. Several extrinsic factors, such as exposure to ionizing radiation, can accelerate senescence. Multiple human and animal studies have reported that exposure to ionizing radiation can have varied effects on organ aging and lead to the prolongation or shortening of life span depending on the radiation dose or dose rate. This paper reviews the effects of radiation on the aging of different types of brain cells, including neurons, microglia, astrocytes, and cerebral endothelial cells. Further, the relevant molecular mechanisms are discussed. Overall, this review highlights how radiation-induced senescence in different cell types may lead to brain aging, which could result in the development of various neurological and neuropsychological disorders. Therefore, treatment targeting radiation-induced oxidative stress and neuroinflammation may prevent radiation-induced brain aging and the neurological and neuropsychological disorders it may cause.

MR Spectroscopy of the Insula: Within- and Between-Session Reproducibility of MEGA-PRESS Measurements of GABA+ and Other Metabolites

The insula plays a critical role in many neuropsychological disorders. Research investigating its neurochemistry with magnetic resonance spectroscopy (MRS) has been limited compared with cortical regions. Here, we investigate the within-session and between-session reproducibility of metabolite measurements in the insula on a 3T scanner. We measure N-acetylaspartate + N-acetylaspartylglutamate (tNAA), creatine + phosphocreatine (tCr), glycerophosphocholine + phosphocholine (tCho), myo-inositol (Ins), glutamate + glutamine (Glx), and γ-aminobutyric acid (GABA) in one cohort using a j-edited MEGA-PRESS sequence. We measure tNAA, tCr, tCho, Ins, and Glx in another cohort with a standard short-TE PRESS sequence as a reference for the reproducibility metrics. All participants were scanned 4 times identically: 2 back-to-back scans each day, on 2 days. Preprocessing was done using LCModel and Gannet. Reproducibility was determined using Pearson’s r, intraclass-correlation coefficients (ICC), coefficients of variation (CV%), and Bland–Altman plots. A MEGA-PRESS protocol requiring averaged results over two 6:45-min scans yielded reproducible GABA measurements (CV% = 7.15%). This averaging also yielded reproducibility metrics comparable to those from PRESS for the other metabolites. Voxel placement inconsistencies did not affect reproducibility, and no sex differences were found. The data suggest that MEGA-PRESS can reliably measure standard metabolites and GABA in the insula.

Examining the Effects of 4He Exposure on the Gut-Brain Axis

Beyond low-Earth orbit, space radiation poses significant risks to astronaut health. Previous studies have shown that the microbial composition of the gastrointestinal (GI) microbiome changes upon exposure to high-linear energy transfer radiation. Interestingly, radiation-induced shifts in GI microbiota composition are linked to various neuropsychological disorders. Herein, we aimed to study changes in GI microbiota and behaviors of rats exposed to whole-body radiation (0, 5 or 25 cGy 4He, 250 MeV/n) at approximately 6 months of age. Fecal samples were collected 24 h prior to 4He irradiation and 24 h and 7 days postirradiation for quantitative PCR analyses to assess fecal levels of spore-forming bacteria (SFB), Bifidobacterium, Lactobacillus and Akkermansia. Rats were also tested in the social odor recognition memory (SORM) test at day 7 after 4He exposure. A subset of rats was euthanized 90 min after completion of the SORM test, and GI tissue from small intestine to colon were prepared for examining overall histological changes and immunohistochemical staining for serotonin (5-HT). No notable pathological changes were observed in GI tissues. Akkermansia spp. and SFB were significantly decreased in the 25 cGy group at 24 h and 7 days postirradiation compared to pre-exposure, respectively. Bifidobacterium and Lactobacillus spp. showed no significant changes. 5-HT production was significantly higher in the proximal small intestine and the cecum in the 25 cGy group compared to the sham group. The 25 cGy group exhibited deficits in recognition in SORM testing at day 7 postirradiation. Taken together, these results suggest a connection between GI microbiome composition, serotonin production, and neurobehavioral performance, and that this connection may be disrupted upon exposure to 25 cGy of 4He ions.

NCOG-09. PREDICTIVE GERIATRIC FACTORS IN ELDERLY PATIENTS TREATED FOR IDH-MUTANT HIGH-GRADE GLIOMAS: A FRENCH POLA NETWORK STUDY

We aimed to describe the characteristics, patterns of care and predictive geriatric factors of elderly patients with IDH-mutant (IDHm) high-grade gliomas (HGG) included in the French POLA network, dedicated to HGG (including 68% of IDHm HGG). For IDHm HGG patients over the age of 70 years, geriatric features were collected: G8 score items (appetite, weight loss, mobility, neuropsychological disorders, body mass index, medications, self-rated health, age), Activities and Instrumental Activities of Daily Living (ADL, IADL) scores, Charlson’s comorbidity Index (CCI) and biological markers. Out of the 1433 HGG patients included in the POLA Network, 119 (8.3%) occurred in patients ≥ 70 years. Among them, 39 presented with IDHm HGG. Of these 39 patients, estimated G8 score was ≤ 14/17 for 16 patients (64%), ADL score was < 6 for 33.3%, IADL score was < 4 for 47% and CCI was ≥ 5 for 72%. Regarding treatment feasibility, 6 of the 19 patients treated by temozolomide prematurely discontinued chemotherapy including 2 for toxicity and 4 for progression. Five of the 10 patients treated by PCV prematurely discontinued chemotherapy, all for toxicity. In multivariate analysis, loss of mobility (p=0.018; p=0.008), severe neuropsychological disorders (p=0.005; p=0.047), body mass index < 21 kg/m2 (p=0.002; p=0.006) and ADL score < 6 (p=0.002; p=0.01) were significantly predictive of poor PFS and OS. Then we generated a specific brain geriatric score including these four items with a sensibility, specificity and AUC for long term survivor (≥ 48 months) of 100%, 83% and 0.948 respectively. Using a cutoff of < 10/13, this score was significantly correlated to PFS and OS (p< 0.001 both). In conclusion, geriatric predictive factors may contribute to the elderly management improvement: the brain geriatric score must now be validated in a prospective independent cohort including IDHm and IDHwt elderly patients.

Association between Resting-state EEG oscillation and psychometric properties in perimenopausal women

Background: The perimenopausal period is associated with higher risk for various mood disorders. Resting-state EEG (rsEEG) brain oscillatory activity has been associated with various neuropsychological disorders and behaviors but has not been assessed in perimenopausal women. Aim: This study aimed to evaluate quantitative relationships between psychometric properties and rsEEG rhythms (δ, θ, α, and γ powers) in perimenopausal women. Methods: A cross-sectional correlational descriptive study was conducted to quantitatively analyze the correlations among rsEEG low to high band activity (δ, θ, α, and γ powers) and psychometric properties for 14 perimenopausal women. Participants completed a psychological inventory comprised of a State Anxiety Inventory (SAI), Depression Inventory (DI), Behavioral Inhibition Scale (BIS), and short-form UPPS Impulsive Behavior Scale (IS) before EEG recording. Results: Results showed that impulsivity was positively related to the β power, symmetrical at most channels (frontal, temporal, central, parietal, and occipital regions; p <.05), but did not relate to the δ, θ, α, and γ powers. The brainwave low to high bands, δ, θ, α, β, and γ power, were not associated with DI, SAI, or BIS scores. Conclusions: This study’s findings suggest that significantly enhanced resting-state beta activity is a trait marker of impulsivity in perimenopausal women. This finding has potential implications for preclinical or clinical evaluation of perimenopausal women.

The Microbiota-Gut-Brain Axis as a Key to Neuropsychiatric Disorders: A Mini Review

The central nervous system (CNS) is closely related to the gastrointestinal tract, mainly through regulating its function and homeostasis. Simultaneously, the gut flora affects the CNS and plays an essential role in the pathogenesis of neurologic and neuropsychological disorders such as Parkinson’s and Alzheimer’s disease, multiple sclerosis, amyotrophic lateral sclerosis or autism spectrum disorder. The population of gut microorganisms contains more than one billion bacteria. The most common are six phyla: Proteobacteria, Actinomyces, Verucomicrobia, Fusobacteria, and dominant Bacteroides with Firmicutes. The microbiota–gut–brain axis is a bidirectional nervous, endocrine, and immune communication between these two organs. They are connected through a variety of pathways, including the vagus nerve, the immune system, microbial metabolites such as short-chain fatty acids (SCFAs), the enteric nervous system, and hormones. Age, diet, antibiotics influence the balance of gut microorganisms and probably lead to the development of neurodegenerative disorders. In this article, a review is presented and discussed, with a specific focus on the changes of gut microbiota, gut–brain axis, related disorders, and the factors that influence gut imbalance.