Secure attachment to caregiver prevents adult depressive symptoms in a sex-dependent manner: A translational study.

Although clinically relevant, evidence for a protective effect of early secure attachment against the development of depressive symptoms in adulthood is still inconsistent. This study used a translational approach to overcome this limitation. The analysis of a non-clinical adult population revealed a moderating effect of secure attachment on depressive symptoms in women only.

Systemic inflammation accelerates neurodegeneration in a rat model of Parkinson's disease overexpressing human alpha synuclein.

Increasing efforts have been made to elucidate how genetic and environmental factors interact in Parkinson's disease (PD). In the present study, we assessed the development of symptoms on a genetic PD rat model that overexpresses human α-synuclein (Snca) at a presymptomatic age, exposed to a pro-inflammatory insult by intraperitoneal injection of lipopolysaccharide (LPS), using immunohistology, high-dimensional flow cytometry, constant potential amperometry, and behavioral analyses. A single injection of LPS into WT and Snca rats triggered long-lasting increase in the activation of pro-inflammatory microglial markers, monocytes, and T lymphocytes.

Unraveling sex differences in Parkinson's disease through explainable machine learning.

Sex differences affect Parkinson's disease (PD) development and manifestation. Yet, current PD identification and treatments underuse these distinctions. Sex-focused PD literature often prioritizes prevalence rates over feature importance analysis.

Neuronal dysfunction and gene modulation by non-coding RNA in Parkinson's disease and synucleinopathies.

Over the last few decades, emerging evidence suggests that non-coding RNAs (ncRNAs) including long-non-coding RNA (lncRNA), microRNA (miRNA) and circular-RNA (circRNA) contribute to the molecular events underlying progressive neuronal degeneration, and a plethora of ncRNAs have been identified significantly misregulated in many neurodegenerative diseases, including Parkinson's disease and synucleinopathy. Although a direct link between neuropathology and causative candidates has not been clearly established in many cases, the contribution of ncRNAs to the molecular processes leading to cellular dysfunction observed in neurodegenerative diseases has been addressed, suggesting that they may play a role in the pathophysiology of these diseases. Aim of the present Review is to overview and discuss recent literature focused on the role of RNA-based mechanisms involved in different aspects of neuronal pathology in Parkinson's disease and synucleinopathy models.

A mouse model of the 3-hit effects of stress: Genotype controls the effects of life adversities in females.

Helplessness is a dysfunctional coping response to stressors associated with different psychiatric conditions. The present study tested the hypothesis that early and adult adversities cumulate to produce helplessness depending on the genotype (3-hit hypothesis of psychopathology). To this aim, we evaluated whether Chronic Unpredictable Stress (CUS) differently affected coping and mesoaccumbens dopamine (DA) responses to stress challenge by adult mice of the C57BL/6J (B6) and DBA/2J (D2) inbred strains depending on early life experience (Repeated Cross Fostering, RCF).

Chemogenetic rectification of the inhibitory tone onto hippocampal neurons reverts autistic-like traits and normalizes local expression of estrogen receptors in the Ambra1+/- mouse model of female autism.

Female, but not male, mice with haploinsufficiency for the proautophagic Ambra1 gene show an autistic-like phenotype associated with hippocampal circuits dysfunctions which include loss of parvalbuminergic interneurons (PV-IN), decrease in the inhibition/excitation ratio, and abundance of immature dendritic spines on CA1 pyramidal neurons. Given the paucity of data relating to female autism, we exploit the Ambra1 female model to investigate whether rectifying the inhibitory input onto hippocampal principal neurons (PN) rescues their ASD-like phenotype at both the systems and circuits level. Moreover, being the autistic phenotype exclusively observed in the female mice, we control the effect of the mutation and treatment on hippocampal expression of estrogen receptors (ER).

The long-lasting effects of early life adversities are sex dependent: The signature of miR-34a.

Background: Exposure to early life adversities (ELA) can influence a plethora of biological mechanisms leading to stress-related disorders later in life through epigenetic mechanisms, such as microRNAs (miRs). MiR-34 is a critical modulator of stress response and stress-induced pathologies and a link between ELA and miR-34a has been reported.

Methods: Here using our well-established model of ELA (Repeated Cross Fostering) we investigate the behavioral long-term effects of ELA in male and female mice.

Morpho-Functional Changes of Nigral Dopamine Neurons in an α-Synuclein Model of Parkinson's Disease.

Background: The accumulation of α-synuclein (α-syn) fibrils in intraneuronal inclusions called Lewy bodies and Lewy neurites is a pathological signature of Parkinson's disease (PD). Although several aspects linked to α-syn-dependent pathology (concerning its spreading, aggregation, and activation of inflammatory and neurodegenerative processes) have been under intense investigation, less attention has been devoted to the real impact of α-syn overexpression on structural and functional properties of substantia nigra pars compacta (SNpc) dopamine (DA) neurons, particularly at tardive stages of α-syn buildup, despite this has obvious relevance to comprehending mechanisms beyond PD progression.

Objectives: We aimed to determine the consequences of a prolonged α-syn overexpression on somatodendritic morphology and functions of SNpc DA neurons.

A multi-expert ensemble system for predicting Alzheimer transition using clinical features.

Alzheimer's disease (AD) diagnosis often requires invasive examinations (e.g., liquor analyses), expensive tools (e.

Early life adversity affecting the attachment bond alters ventral tegmental area transcriptomic patterning and behavior almost exclusively in female mice.

Early life experiences that affect the attachment bond formation can alter developmental trajectories and result in pathological outcomes in a sex-related manner. However, the molecular basis of sex differences is quite unknown. The dopaminergic system originating from the ventral tegmental area has been proposed to be a key mediator of this process.

Resilience to anhedonia-passive coping induced by early life experience is linked to a long-lasting reduction of I current in VTA dopaminergic neurons.

Exposure to aversive events during sensitive developmental periods can affect the preferential coping strategy adopted by individuals later in life, leading to either stress-related psychiatric disorders, including depression, or to well-adaptation to future adversity and sources of stress, a behavior phenotype termed "resilience". We have previously shown that interfering with the development of mother-pups bond with the Repeated Cross Fostering (RCF) stress protocol can induce resilience to depression-like phenotype in adult C57BL/6J female mice. Here, we used patch-clamp recording in midbrain slice combined with both and pharmacology to test our hypothesis of a link between electrophysiological modifications of dopaminergic neurons in the intermediate Ventral Tegmental Area (VTA) of RCF animals and behavioral resilience.

MicroRNA-34a regulates 5-HT2C expression in dorsal raphe and contributes to the anti-depressant-like effect of fluoxetine.

Selective serotonin reuptake inhibitors (SSRIs) are designed to improve mood by raising extracellular serotonin levels through the blockade of the serotonin transporter. However, they exhibit a slow onset of action, suggesting the involvement of adaptive regulatory mechanisms. We hypothesized that the microRNA-34 family facilitates the therapeutic activity of SSRIs.

Long term effects of early life stress on HPA circuit in rodent models.

Adaptation to environmental challenges represents a critical process for survival, requiring the complex integration of information derived from both external cues and internal signals regarding current conditions and previous experiences. The Hypothalamic-pituitary-adrenal axis plays a central role in this process inducing the activation of a neuroendocrine signaling cascade that affects the delicate balance of activity and cross-talk between areas that are involved in sensorial, emotional, and cognitive processing such as the hippocampus, amygdala, Prefrontal Cortex, Ventral Tegmental Area, and dorsal raphe. Early life stress, especially early critical experiences with caregivers, influences the functional and structural organization of these areas, affects these processes in a long-lasting manner and may result in long-term maladaptive and psychopathological outcomes, depending on the complex interaction between genetic and environmental factors.

RISC RNA sequencing in the Dorsal Raphè reveals microRNAs regulatory activities associated with behavioral and functional adaptations to chronic stress.

The Dorsal Raphe (DR) is the primary source of serotonergic input in the brain and a center for the homeostatic maintenance of the serotonergic tone. Under repeated stimulation, it can undergo adaptive modifications that alter serotonergic neurotransmission, which can lead to behavioral dysfunction. Post-transcriptional regulation by microRNAs is implicated in these adaptations.

Xlr4 as a new candidate gene underlying vulnerability to cocaine effects.

Although several studies have been performed in rodents, non-human primates and humans, the biological basis of vulnerability to develop cocaine addiction remains largely unknown. Exposure to critical early events (as Repeated Cross Fostering (RCF)) has been reported to increase sensitivity to cocaine effects in adult C57BL/6J female mice. Using a microarray approach, here we report data showing a strong engagement of X-linked lymphocyte-regulated 4a and 4b (Xlr4) genes in cocaine effects.

MicroRNA-34a Regulates the Depression-like Behavior in Mice by Modulating the Expression of Target Genes in the Dorsal Raphè.

Chronic stress exposure is known to increase vulnerability to the expression of psychiatric disorders, such as depression. Clinical and preclinical evidences support the involvement of the microRNA-34 family in stress-related psychiatric conditions and in the regulation of stress responses. However, the mechanism and the multiple targets by which the microRNA-34 family can affect the stress response and stress-related behavioral alteration are not fully known.

Sex-dependent effects of early unstable post-natal environment on response to positive and negative stimuli in adult mice.

Alterations in early environmental conditions that interfere with the creation of a stable mother-pup bond have been suggested to be a risk factor for the development of stress-related psychopathologies later in life. The long-lasting effects of early experiences are mediated by changes in various cerebral circuits, such as the corticolimbic system, which processes aversive and rewarding stimuli. However, it is evident that the early environment is not sufficient per se to induce psychiatric disorders; interindividual (eg, sex-based) differences in the response to environmental challenges exist.