Promoting sleep health during pregnancy for enhancing women's health: a longitudinal randomized controlled trial combining biological, physiological and psychological measures, Maternal Outcome after THERapy for Sleep (MOTHERS).

BACKGROUND: Sleep is vital for maintaining individuals' physical and mental health and is particularly challenged during pregnancy. More than 70% of women during the gestational period report insomnia symptoms. Sleep dysfunction in the peripartum increases the risk for a cascade of negative health outcomes during late pregnancy, birth, and postpartum. While psychological interventions are considered the first line treatment for sleep difficulties, they are still scarcely offered during pregnancy and there is a lack of longitudinal research combining psychological and physiological indices. METHODS: The present protocol outlines a randomized controlled trial aimed at testing the long-term effectiveness of an automatized digitalized psychoeducational intervention for insomnia for expectant mothers complaining insomnia symptoms without comorbidity. Outcomes include physiological, hormonal, and subjective indices of maternal psychopathology, stress, and emotional processes, and sleep and wellbeing of the family system. The trial is part of a longitudinal study evaluating expectant mothers from early pregnancy (within the 15th gestational week) to 6-months postpartum through 6 observational phases: baseline (BSL), 6- and 12-weeks from BSL (FU1-FU2), 2-to-4 weeks after delivery (FU3), and 3- and 6-months after delivery (FU4-5). We plan to recruit 38 women without sleep difficulties (Group A) and 76 women with sleep difficulties (Group B). Group B will be randomly assigned to digital psychological control intervention (B1) or experimental psychoeducational intervention targeting insomnia (B2). At 3 time points, an ecological-momentary-assessment (EMA) design will be used to collect data on sleep and emotions (diaries), sleep-wake parameters (actigraphy) and stress reactivity (salivary cortisol). We will also test the DNA methylation of genes involved in the stress response as biomarkers of prenatal poor sleep. Information on partner's insomnia symptoms and new-borns' sleep will be collected at each stage. DISCUSSION: The proposed protocol aims at testing an easily accessible evidence-based psychoeducational intervention for expectant mothers to help them improving sleep, health, and wellbeing in the peripartum. The results could improve the understanding and management of sleep difficulties and peripartum depression. TRIAL REGISTRATION: The study protocol has been registered on 22 April 2024 with ClinicalTrials.gov Protocol Registration and Results System (PRS), ID: NCT06379074. PROTOCOL VERSION: April 23, 2024.

Correction: Cutuli et al. Neuroprotective Role of Dietary Supplementation with Omega-3 Fatty Acids in the Presence of Basal Forebrain Cholinergic Neurons Degeneration in Aged Mice. Int. J. Mol. Sci. 2020, 21, 1741.

The authors wish to make the following corrections to this paper [...].

The impact of COVID-19 on Italian adolescents' sleep and its association with psychological factors.

Insomnia and circadian dysregulation during adolescence represent important risk factors for emotional and psychological problems. Recent studies have shown that the coronavirus disease 2019 (COVID-19) pandemic has been linked to a high prevalence of behavioural sleep problems in the general population. This study aimed to provide two pictures of two different time points of the pandemic regarding the prevalence of sleep problems in adolescents and their association with psychological health variables. Two different independent large samples of Italian adolescents aged 13-17 years were recruited at two pandemic time points. A total of 1,146 adolescents at Time 1 (T1; April 2020) and 1,406 at Time 2 (T2; April 2021) took part in the study. Measures of insomnia symptoms, sleep hygiene, chronotype, psychological distress and emotion regulation were collected. Prevalence of insomnia was 12.13% at T1 and 23.19% at T2. Furthermore, high levels of poor sleep habits (late bedtime, poor sleep hygiene, use of electronic devices at bedtime) were also detected at both time points. Insomnia symptoms strongly correlated with poor sleep hygiene, higher psychological distress, and emotional suppression at both time points. Results highlighted an alarming picture for two large samples at two different time points of the pandemic that showed a potential negative impact of the COVID-19 pandemic, in both the first outbreak and in the later phase of the pandemic, on sleep habits, psychological distress and insomnia symptoms in adolescents. This strongly suggests the need for monitoring these variables and their interaction in the post-pandemic period and to develop and promote interventions for insomnia and circadian disturbances during adolescence.

Psychological correlates of insomnia in professional soccer players: An exploratory study.

Sleep promotes health, well-being, recovery and athletic performance. As a consequence, sleep problems in athletes may have detrimental effects. Previous investigations showed that professional athletes often reported to suffer of poor sleep quality and insomnia (e.g. difficulties falling asleep and/or maintaining sleep). However, psychological variables exacerbating and maintaining insomnia in professional athletes as well as its mechanistic pathways are still largely unknown. Available literature mostly focused on effects of sport-related variables, such as evening training and stimulant consumption on athletes' sleep. Instead, the contribution of cognitive and emotional variables globally associated with insomnia in athletes in clinical models has been largely neglected. To address these limitations, this study explored the associations between emotional experience, pre-sleep arousal, pre-sleep worry and rumination and insomnia severity in a sample of 210 (25.93 ± 6.68 years) male professional soccer players. Bivariate correlations, multiple regression, and structural equation modelling with manifest variables (path analysis) were computed. Results showed that insomnia severity was associated with stimulants consumption, pre-sleep arousal, negative emotions, positive emotions, and pre-sleep worry/rumination (all p < .05). Path analysis showed that relationship between stimulant consumption, emotional experience, worry/rumination and insomnia was mediated by pre-sleep arousal (p < .05). Our results suggest that preventive and interventional studies in professional soccer players would benefit from considering global cognitive-emotional variables as targets of interventions.HighlightsInsomnia was associated with greater stimulants consumption, pre-sleep arousal, negative emotions, pre-sleep worry/rumination, and lower positive emotions.Path analysis showed that pre-sleep arousal mediated the relationship between stimulant consumption, emotional experience, worry/rumination and insomnia severity.Cognitive-emotional and behavioural factors as well as sport-related variables were important predictors of insomnia in professional soccer players.

Sleep Characteristics in Italian Children During Home Confinement Due to Covid-19 Outbreak.

OBJECTIVE: Italy faced one of the first large clusters of COVID-19 infections worldwide. Home confinement and social distancing could have negatively impacted sleep habits and prevalence of sleep disorders in children, which may be also linked with altered emotional processes. The present study focused on clinical aspects related to sleep, insomnia and emotions in Italian children aged 0-to-12 years during home confinement due to COVID-19 outbreak. METHOD: An online survey was systematically distributed in all Italian territories by contacting regional offices of the Italian Ministry of Instruction, University and Research (MIUR) and schools with available contact. All respondents had to be parents of at least one child aged 0 to 12 years old. Information on sociodemographic variables, sleep habits, sleep health behaviors, sleep disorders and mood were collected. RESULTS: Parents of 2361 children (mean age: 8.1 ± 2.62 years; 1148 females; 1213 males) answered the survey. 1.2% of children was between 0 and 2 years old; 15.3% within 3 to 5 years and 83.3% within 6 and 12 years. In all group ages, late bedtime was observed (most of them after 9 p.m.). 59.4% of all children presented at least one clinical diagnostic criterion for childhood insomnia. Logistic regression model showed that presence of at least one criterion for childhood insomnia was associated to younger age, negative mood, current parental insomnia, being the only child, presence of any other sleep disorder, and sleep hygiene behaviors. CONCLUSIONS: Data indicate an alarming increase of prevalence of insomnia related problems in Italian children during home confinement with respect to previous data. This was found to be associated with poor sleep hygiene and negative mood. Clinical programs targeting insomnia, sleep health behaviors and emotional processes should be implemented in pediatric primary care in order to prevent the development of sleep problems in a post-pandemic situation.

The Association between Diurnal Sleep Patterns and Emotions in Infants and Toddlers Attending Nursery.

BACKGROUND: Childcare programs often include mandatory naptime during the day. Loss of daytime sleep could lead to a moderate-to-large decrease in self-regulation, emotion processing, and learning in early childhood. Nevertheless, daytime sleep has been less accurately studied than nighttime sleep. This study aims to explore the relationship between diurnal sleep habits in nursery settings, nocturnal sleep quality, and post-nap emotional intensity in infants and toddlers. METHODS: Data of 92 children (52 girls, 40 boys) aged 6 to 36 months were obtained. Sleep habits as well as positive and negative emotions were monitored by educators during nursery times through a sleep and emotion diary for two weeks. RESULTS: Explorative analyses showed that diurnal sleep hours decreased across age groups (except for females aged 25-36 months) and that all age groups had a lower amount of nocturnal sleep than is recommended by the National Sleep Foundation. Partial correlation analysis showed significant correlation between daytime sleep onset latency and positive emotions. Mediation analyses showed that daytime napping is relevant for emotional functioning independently of nocturnal sleep quality. CONCLUSIONS: Daytime sleep in early childhood seems to be linked to the management of positive and negative emotions and could play a role in healthy development of emotional processes.

Behavioral, neuromorphological, and neurobiochemical effects induced by omega-3 fatty acids following basal forebrain cholinergic depletion in aged mice.

BACKGROUND: In recent years, mechanistic, epidemiologic, and interventional studies have indicated beneficial effects of omega-3 polyunsaturated fatty acids (n-3 PUFA) against brain aging and age-related cognitive decline, with the most consistent effects against Alzheimer's disease (AD) confined especially in the early or prodromal stages of the pathology. In the present study, we investigated the action of n-3 PUFA supplementation on behavioral performances and hippocampal neurogenesis, volume, and astrogliosis in aged mice subjected to a selective depletion of basal forebrain cholinergic neurons. Such a lesion represents a valuable model to mimic one of the most reliable hallmarks of early AD neuropathology. METHODS: Aged mice first underwent mu-p75-saporin immunotoxin intraventricular lesions to obtain a massive cholinergic depletion and then were orally supplemented with n-3 PUFA or olive oil (as isocaloric control) for 8 weeks. Four weeks after the beginning of the dietary supplementation, anxiety levels as well as mnesic, social, and depressive-like behaviors were evaluated. Subsequently, hippocampal morphological and biochemical analyses and n-3 PUFA brain quantification were carried out. RESULTS: The n-3 PUFA treatment regulated the anxiety alterations and reverted the novelty recognition memory impairment induced by the cholinergic depletion in aged mice. Moreover, n-3 PUFA preserved hippocampal volume, enhanced neurogenesis in the dentate gyrus, and reduced astrogliosis in the hippocampus. Brain levels of n-3 PUFA were positively related to mnesic abilities. CONCLUSIONS: The demonstration that n-3 PUFA are able to counteract behavioral deficits and hippocampal neurodegeneration in cholinergically depleted aged mice promotes their use as a low-cost, safe nutraceutical tool to improve life quality at old age, even in the presence of first stages of AD.

Interventions to reduce occupational stress and burn out within neonatal intensive care units: a systematic review.

Occupational stress is an emerging problem among physician and nurses, and those working in intensive care settings are particularly exposed to the risk of developing burnout. To verify what types of interventions to manage occupational stress and burn out within neonatal intensive care units (NICUs) have been introduced so far and to verify their efficacy among caregivers. PsycINFO (PsycINFO 1967-July week 3 2019), Embase (Embase 1996-2019 week 29) e Medline (Ovid MEDLINE(R) without revisions 1996-July week 2 2019) were systematically searched combining MeSH and free text terms for "burn out" AND "healthcare provider" AND "NICU". Inclusion criteria were interventions directed to healthcare providers settled in NICUs. Only English language papers were included. Six articles were included in the final analysis. All the studies reported an overall efficacy of the interventions in reducing work-related stress, both when individual focused and organisation directed. The analysis revealed low quality of the studies and high heterogeneity in terms of study design, included populations, interventions and their evaluation assessment. There is currently very limited evidence regarding the management of occupational stress and burn out within NICUs. The quality of available studies was suboptimal. The peculiarities of the NICUs should be considered when developing strategies for occupational stress management. Training self-awareness of workers regarding their reactions to the NICU environment, also from the pre-employment stage, could be an additional approach to prevent and manage stress.

Neuroprotective Role of Dietary Supplementation with Omega-3 Fatty Acids in the Presence of Basal Forebrain Cholinergic Neurons Degeneration in Aged Mice.

As major components of neuronal membranes, omega-3 polyunsaturated fatty acids (n-3 PUFA) exhibit a wide range of regulatory functions. Recent human and animal studies indicate that n-3 PUFA may exert beneficial effects on aging processes. Here we analyzed the neuroprotective influence of n-3 PUFA supplementation on behavioral deficits, hippocampal neurogenesis, volume loss, and astrogliosis in aged mice that underwent a selective depletion of basal forebrain cholinergic neurons. Such a lesion represents a valid model to mimic a key component of the cognitive deficits associated with dementia. Aged mice were supplemented with n-3 PUFA or olive oil (as isocaloric control) for 8 weeks and then cholinergically depleted with mu-p75-saporin immunotoxin. Two weeks after lesioning, mice were behaviorally tested to assess anxious, motivational, social, mnesic, and depressive-like behaviors. Subsequently, morphological and biochemical analyses were performed. In lesioned aged mice the n-3 PUFA pre-treatment preserved explorative skills and associative retention memory, enhanced neurogenesis in the dentate gyrus, and reduced volume and VAChT levels loss as well as astrogliosis in hippocampus. The present findings demonstrating that n-3 PUFA supplementation before cholinergic depletion can counteract behavioral deficits and hippocampal neurodegeneration in aged mice advance a low-cost, non-invasive preventive tool to enhance life quality during aging.

Insomnia in the Italian Population During Covid-19 Outbreak: A Snapshot on One Major Risk Factor for Depression and Anxiety.

Objectives: One of the largest clusters of Covid-19 infections was observed in Italy. The population was forced to home confinement, exposing individuals to increased risk for insomnia, which is, in turn, associated with depression and anxiety. Through a cross-sectional online survey targeting all Italian adult population (≥18 yrs), insomnia prevalence and its interactions with relevant factors were investigated. Methods: The survey was distributed from 1st April to 4th May 2020. We collected information on insomnia severity, depression, anxiety, sleep hygiene behaviors, dysfunctional beliefs about sleep, circadian preference, emotion regulation, cognitive flexibility, perceived stress, health habits, self-report of mental disorders, and variables related to individual difference in life changes due to the pandemic's outbreak. Results: The final sample comprised 1,989 persons (38.4 ± 12.8 yrs). Prevalence of clinical insomnia was 18.6%. Results from multivariable linear regression showed that insomnia severity was associated with poor sleep hygiene behaviors [ß = 0.11, 95% CI (0.07-0.14)]; dysfunctional beliefs about sleep [ß = 0.09, 95% CI (0.08-0.11)]; self-reported mental disorder [ß = 2.51, 95% CI (1.8-3.1)]; anxiety [ß = 0.33, 95% CI (0.25-0.42)]; and depression [ß = 0.24, 95% CI (0.16-0.32)] symptoms. Conclusion: An alarming high prevalence of clinical insomnia was observed. Results suggest that clinical attention should be devoted to problems of insomnia in the Italian population with respect to both prevention and treatment.

Interventions for sleep problems during pregnancy: A systematic review.

Sleep problems during pregnancy are prevalent and could be linked to negative outcomes during pregnancy or post-partum. However, these complaints are often underdiagnosed and undertreated. This review aimed to systematically assess the effectiveness of different interventions to ameliorate poor sleep quality and insomnia during pregnancy. Pubmed, PsycINFO and Medline databases were systematically searched without publication period restriction until 3rd May 2019. Eligible studies had to: include pregnant women of any age and gestational age; use clinical intervention designs targeted at improving sleep outcome; report pre- and post-treatment data for one or more sleep-related outcomes; be published in English, Italian, German, Spanish, or French. Sixteen studies were selected including 1252 expecting mothers. Studies evaluated the efficacy of various interventions: cognitive behavioral interventions for insomnia (4); pharmacotherapy (1); acupuncture (1); mindfulness and yoga (3); relaxation (5) and herbal medication (2). Only six were randomized controlled trials, and only four evaluated longitudinal outcomes. Preliminary support was found for all interventions, but our knowledge is still too limited by lack of evidence. There is an utmost urgency to perform high-quality randomized controlled trials for insomnia interventions during pregnancy and to implement effective programs in standard gynecological care.

Mindfulness and metacognition in facing with fear of recurrence: A proof-of-concept study with breast-cancer women.

OBJECTIVE: Fear of recurrence is a crucial issue in cancer care. On the one hand, the increase of cancer-survival rates and complexity of care is exposing patients to this type of fear. On the other hand, it is a distressing and recurrent psychosocial risk that affects quality of life and adherence to follow-up. Patients should have access to targeted psychological interventions aimed at reducing or preventing fear of recurrence. This mixed-methods pilot study reports the preliminary results of a novel mindfulness- and metacognition-based intervention specifically targeting fear of recurrence. METHODS: The study was composed of an individual (n = 76) and a group (n = 38) intervention, both lasting 8 weeks, that were evaluated through a preassessment and postassessment and a 1-month follow-up. We enrolled women recovering from breast cancer (n = 114) in follow-up care, with significant psychosocial distress. Patients with more severe psychopathology were assigned to the individual treatment, whereas the less severe ones were assigned to the group treatment. We explored the distress and the fear of recurrence through standardized measures and in-depth qualitative interviews. RESULTS: Results showed that depressive, anxious, and post-traumatic symptoms were reduced significantly in the entire sample. Patients reported a significant reduction of fear of recurrence, which was described in terms of loss of control, increase of uncertainty, and decrease of metacognitive and interpersonal skills. CONCLUSIONS: Although further studies are needed, these findings provide preliminary proof-of-concept results for the potential of integrated mindfulness- and metacognition-based interventions to reduce fear of recurrence in cancer patients.

Effects of pre-reproductive maternal enrichment on maternal care, offspring's play behavior and oxytocinergic neurons.

Potentiating social, cognitive, and sensorimotor stimulations the Environmental Enrichment (EE) increases levels of novelty and complexity experienced by individuals. Growing evidence demonstrates that parental EE experience, even occurring in the pre-reproductive phase, affects behavioral and neural developmental trajectories of the offspring. To discover how the accumulation of early maternal complex experiences may inform and shape the social behavior of the following generation, we examined the effects of pre-reproductive enrichment of dams (post-natal days 21-72) on the play performances of their male and female adolescent offspring. Furthermore, we examined the effects of pre-reproductive enrichment on maternal behavior (during post-partum days 1-10) and male intruder aggression (on post-partum day 11). Since oxytocin modulates maternal care, social bonding, and agonistic behavior, the number of oxytocinergic neurons of the paraventricular (PVN) and supraoptic (SON) nuclei was examined in both dams and offspring. Results revealed that enriched females exhibited higher levels of pup-oriented behaviors, especially Crouching, and initiated pup-retrieval more quickly than standard females after the maternal aggression test. Such behavioral peculiarities were accompanied by increased levels of oxytocinergic neurons in PVN and SON. Moreover, pre-reproductive maternal EE cross-generationally influenced the offspring according to sex. Indeed, male pups born to enriched females exhibited a reduced play fighting associated with a higher number of oxytocinergic neurons in SON in comparison to male pups born to standard-housed females. In conclusion, pre-reproductive EE to the mothers affects their maternal care and has a cross-generational impact on the social behavior of their offspring that do not directly experiences EE. This article is part of the Special Issue entitled "Neurobiology of Environmental Enrichment".

Considering Sleep, Mood, and Stress in a Family Context: A Preliminary Study.

BACKGROUND: During the first years of life, parental sleep strongly depends on child's sleep quality. Poor parental sleep may relate to increased stress and negative mood. However, there is a lack of sleep studies focusing on all family members. This study aimed to investigate the relationship between sleep, mood, and stress in mothers, fathers and children. METHODS: Data were obtained from 65 parental couples and 65 children (2 to 36 months). Data on sleep for all family members and stress of parents were completed by both mothers and fathers through questionnaires and sleep diaries. RESULTS: Toddlers' positive mood before nocturnal sleep was significantly associated with reduced wake times after sleep onset. Mothers reported worse sleep quality compared to fathers. Shorter sleep onset latency in fathers and better sleep efficiency in mothers were linked with better self-reported mood upon awakening. In mothers, but not in fathers, poor sleep quality was associated with higher perceived stress. CONCLUSION: Results suggest bidirectional relationships between sleep and mood in children, mothers and fathers. Moreover, results evidence poorer sleep in mothers, compared to fathers, which was linked with increased parenting stress. This gender gap should be further considered in studies with larger samples and in clinical contexts.

Influence of Pre-reproductive Maternal Enrichment on Coping Response to Stress and Expression of c-Fos and Glucocorticoid Receptors in Adolescent Offspring.

Environmental enrichment (EE) is an experimental setting broadly used for investigating the effects of complex social, cognitive, and sensorimotor stimulations on brain structure and function. Recent studies point out that parental EE experience, even occurring in the pre-reproductive phase, affects neural development and behavioral trajectories of the offspring. In the present study we investigated the influences of pre-reproductive EE of female rats on maternal behavior and adolescent male offspring's coping response to an inescapable stressful situation after chronic social isolation. For this purpose female Wistar rats were housed from weaning to breeding age in enriched or standard environments. Subsequently, all females were mated and housed in standard conditions until offspring weaning. On the first post partum day (ppd 1), mother-pup interactions in undisturbed conditions were recorded. Further, after weaning the male pups were reared for 2 weeks under social isolation or in standard conditions, and then submitted or not to a single-session Forced Swim Test (FST). Offspring's neuronal activation and plastic changes were identified by immunohistochemistry for c-Fos and glucocorticoid receptors (GRs), and assessed by using stereological analysis. The biochemical correlates were measured in the hippocampus, amygdala and cingulate cortex, structures involved in hypothalamic-pituitary-adrenocortical axis regulation. Enriched dams exhibited increased Crouching levels in comparison to standard reared dams. In the offspring of both kinds of dams, social isolation reduced body weight, decreased Immobility, and increased Swimming during FST. Moreover, isolated offspring of enriched dams exhibited higher levels of Climbing in comparison to controls. Interestingly, in the amygdala of both isolated and control offspring of enriched dams we found a lower number of c-Fos immunopositive cells in response to FST and a higher number of GRs in comparison to the offspring of standard dams. These results highlight the profound influence of a stressful condition, such as the social isolation, on the brain of adolescent rats, and underline intergenerational effects of maternal experiences in regulating the offspring response to stress.

Dopamine neuronal loss contributes to memory and reward dysfunction in a model of Alzheimer's disease.

Alterations of the dopaminergic (DAergic) system are frequently reported in Alzheimer's disease (AD) patients and are commonly linked to cognitive and non-cognitive symptoms. However, the cause of DAergic system dysfunction in AD remains to be elucidated. We investigated alterations of the midbrain DAergic system in the Tg2576 mouse model of AD, overexpressing a mutated human amyloid precursor protein (APPswe). Here, we found an age-dependent DAergic neuron loss in the ventral tegmental area (VTA) at pre-plaque stages, although substantia nigra pars compacta (SNpc) DAergic neurons were intact. The selective VTA DAergic neuron degeneration results in lower DA outflow in the hippocampus and nucleus accumbens (NAc) shell. The progression of DAergic cell death correlates with impairments in CA1 synaptic plasticity, memory performance and food reward processing. We conclude that in this mouse model of AD, degeneration of VTA DAergic neurons at pre-plaque stages contributes to memory deficits and dysfunction of reward processing.

Chronic Lithium Treatment in a Rat Model of Basal Forebrain Cholinergic Depletion: Effects on Memory Impairment and Neurodegeneration.

Alzheimer's disease (AD) is an age-related neurodegenerative disorder with multifactorial etiopathogenesis, characterized by progressive loss of memory and other cognitive functions. A fundamental neuropathological feature of AD is the early and severe brain cholinergic neurodegeneration. Lithium is a monovalent cation classically utilized in the treatment of mood disorders, but recent evidence also advances a beneficial potentiality of this compound in neurodegeneration. Interestingly, lithium acts on several processes whose alterations characterize the brain cholinergic impairment at short and long term. On this basis, the aim of the present research was to evaluate the potential beneficial effects of a chronic lithium treatment in preventing the damage that a basal forebrain cholinergic neurodegeneration provokes, by investigating memory functions and neurodegeneration correlates. Adult male rats were lesioned by bilateral injections of the immunotoxin 192 IgG-Saporin into the basal forebrain. Starting 7 days before the surgery, the animals were exposed to a 30-day lithium treatment, consisting of a 0.24% Li2CO3 diet. Memory functions were investigated by the open field test with objects, the sociability and preference for social novelty test, and the Morris water maze. Hippocampal and neocortical choline acetyltransferase (ChAT) levels and caspase-3 activity were determined. Cholinergic depletion significantly impaired spatial and social recognition memory, decreased hippocampal and neocortical ChAT levels and increased caspase-3 activity. The chronic lithium treatment significantly rescued memory performances but did not modulate ChAT availability and caspase-3 activity. The present findings support the lithium protective effects against the cognitive impairment that characterizes the brain cholinergic depletion.

Effects of Anti-NMDA Antibodies on Functional Recovery and Synaptic Rearrangement Following Hemicerebellectomy.

The compensation that follows cerebellar lesions is based on synaptic modifications in many cortical and subcortical regions, although its cellular mechanisms are still unclear. Changes in glutamatergic receptor expression may represent the synaptic basis of the compensated state. We analyzed in rats the involvement of glutamatergic system of the cerebello-frontal network in the compensation following a right hemicerebellectomy. We evaluated motor performances, spatial competencies and molecular correlates in compensated hemicerebellectomized rats which in the frontal cortex contralateral to the hemicerebellectomy side received injections of anti-NMDA antibodies from patients affected by anti-NMDA encephalitis. In the compensated hemicerebellectomized rats, the frontal injections of anti-NMDA antibodies elicited a marked decompensation state characterized by slight worsening of the motor symptoms as well as severe impairment of spatial mnesic and procedural performances. Conversely, in the sham-operated group the frontal injections of anti-NMDA antibodies elicited slight motor and spatial impairment. The molecular analyses indicated that cerebellar compensatory processes were related to a relevant rearrangement of glutamatergic synapses (NMDA and AMPA receptors and other glutamatergic components) along the entire cortico-cerebellar network. The long-term maintenance of the rearranged glutamatergic activity plays a crucial role in the maintenance of recovered function.

Maintenance of aversive memories shown by fear extinction-impaired phenotypes is associated with increased activity in the amygdaloid-prefrontal circuit.

Although aversive memory has been mainly addressed by analysing the changes occurring in average populations, the study of neuronal mechanisms of outliers allows understanding the involvement of individual differences in fear conditioning and extinction. We recently developed an innovative experimental model of individual differences in approach and avoidance behaviors, classifying the mice as Approaching, Balancing or Avoiding animals according to their responses to conflicting stimuli. The approach and avoidance behaviors appear to be the primary reactions to rewarding and threatening stimuli and may represent predictors of vulnerability (or resilience) to fear. We submitted the three mice phenotypes to Contextual Fear Conditioning. In comparison to Balancing animals, Approaching and Avoiding mice exhibited no middle- or long-term fear extinction. The two non-extinguishing phenotypes exhibited potentiated glutamatergic neurotransmission (spontaneous excitatory postsynaptic currents/spinogenesis) of pyramidal neurons of medial prefrontal cortex and basolateral amygdala. Basing on the a priori individuation of outliers, we demonstrated that the maintenance of aversive memories is linked to increased spinogenesis and excitatory signaling in the amygdala-prefrontal cortex fear matrix.