Integrating early life stress in neurological disease: advancing preventive neurology.

Background: In 2021, an estimated 43% of the world's population had been diagnosed with a neurological disorder. Early life stress (ELS) is now a well-established risk factor for later-life neurological disorders. However, translation to clinical practice is hindered by oversimplification, lack of standardisation and limited knowledge of the patterns and mechanisms of disease pathogenesis.

A Systematic Review and Narrative Synthesis of Cognitive Training in the Treatment of Mental Illness and Substance Use Disorder.

The one unifying and distinguishing feature of all neuropsychiatric illnesses is the co-occurrence of cognitive dysfunction. Cognitive training (CT) was developed to enhance neural connectivity and cognition and improve day-to-day functioning. However, the benefits of CT are still debated.

The Impact of Free and Added Sugars on Cognitive Function: A Systematic Review and Meta-Analysis.

A relationship between excessive sugar consumption and cognitive function has been described in animal models, but the specific effects of sugars in humans remains unclear. This systematic review and meta-analysis aimed to evaluate the current knowledge, research characteristics, and quality of evidence of studies investigating the impacts of free and added sugars on human cognition in healthy participants. The review identified 77 studies (65 experimental trials, = 3831; 9 cross-sectional studies, = 11,456; and 3 cohort studies, = 2059).

The Impact of Free Sugar on Human Health-A Narrative Review.

The importance of nutrition in human health has been understood for over a century. However, debate is ongoing regarding the role of added and free sugars in physiological and neurological health. In this narrative review, we have addressed several key issues around this debate and the major health conditions previously associated with sugar.

Development and use of a high-throughput screen to identify novel modulators of the corticotropin releasing factor binding protein.

Background: Stress responses are believed to involve corticotropin releasing factor (CRF), its two cognate receptors (CRF and CRF), and the CRF-binding protein (CRFBP). Whereas decades of research has focused on CRF, the role of CRF in the central nervous system (CNS) has not been thoroughly investigated. We have previously reported that CRF, interacting with a C terminal fragment of CRFBP, CRFBP(10kD), may have a role in the modulation of neuronal activity.

Neural serotonergic circuits for controlling long-term voluntary alcohol consumption in mice.

Alcohol-use-disorders are chronic relapsing illnesses, often co-morbid with anxiety. We have previously shown using the "drinking-in-the-dark" model in mice that the stimulation of the serotonin receptor 1A (5-HT) reduces ethanol binge-drinking behaviour and withdrawal-induced anxiety. The 5-HT receptor is located either on Raphe neurons as autoreceptors, or on target neurons as heteroreceptors.

Retrieval of olfactory fear memory alters cell proliferation and expression of pCREB and pMAPK in the corticomedial amygdala and piriform cortex.

The brain forms robust associations between odors and emotionally salient memories, making odors especially effective at triggering fearful or traumatic memories. Using Pavlovian olfactory fear conditioning (OFC), a variant of the traditional tone-shock paradigm, this study explored the changes involved in its processing. We assessed the expression of neuronal plasticity markers phosphorylated cyclic adenosine monophosphate response element binding protein (pCREB) and phosphorylated mitogen-activated protein kinase (pMAPK) 24 h and 14 days following OFC, in newborn neurons (EdU+) and in brain regions associated with olfactory memory processing; the olfactory bulb, piriform cortex, amygdale, and hippocampus.

Dissecting the contribution of 5-HT auto- and heteroreceptors in sucrose overconsumption in mice.

The rise in obesity prevalence has been linked to overconsumption of high-sugar containing food and beverages. Recent evidence suggests that chronic sucrose consumption leads to changes in serotonergic neuroplasticity within the neural circuits involved in feeding control. Although there is a relationship between serotonin signalling in the brain and diet-induced obesity, the specific serotonin (5-HT) receptors or pathways involved remain unknown.

Contextual Fear Memory Maintenance Changes Expression of pMAPK, BDNF and IBA-1 in the Pre-limbic Cortex in a Layer-Specific Manner.

Post-traumatic stress disorder (PTSD) is a debilitating and chronic fear-based disorder. Pavlovian fear conditioning protocols have long been utilised to manipulate and study these fear-based disorders. Contextual fear conditioning (CFC) is a particular Pavlovian conditioning procedure that pairs fear with a particular context.

Sucrose Consumption Alters Serotonin/Glutamate Co-localisation Within the Prefrontal Cortex and Hippocampus of Mice.

The overconsumption of sugar-sweetened food and beverages underpins the current rise in obesity rates. Sugar overconsumption induces maladaptive neuroplasticity to decrease dietary control. Although serotonin and glutamate co-localisation has been implicated in reward processing, it is still unknown how chronic sucrose consumption changes this transmission in regions associated with executive control over feeding-such as the prefrontal cortex (PFC) and dentate gyrus (DG) of the hippocampus.

Long-Term Overconsumption of Sugar Starting at Adolescence Produces Persistent Hyperactivity and Neurocognitive Deficits in Adulthood.

Sugar has become embedded in modern food and beverages. This has led to overconsumption of sugar in children, adolescents, and adults, with more than 60 countries consuming more than four times (>100 g/person/day) the WHO recommendations (25 g/person/day). Recent evidence suggests that obesity and impulsivity from poor dietary habits leads to further overconsumption of processed food and beverages.

A binge high sucrose diet provokes systemic and cerebral inflammation in rats without inducing obesity.

While the dire cardiometabolic consequences of the hypercaloric modern 'Western' diet are well known, there is not much information on the health impact of a high sucrose diet not inducing weight gain. Here, we tested the hypothesis that rats reared with intermittent binge access to sucrose in addition to normal chow would develop an inflammatory response in brain. To test this hypothesis, we undertook serial PET/MRI scans with the TSPO ligand [F]DPA714 in a group of (n=9) rats at baseline and again after voluntarily consuming 5% sucrose solution three days a week for three months.

Tumour Necrosis Factor in Neuroplasticity, Neurogenesis and Alcohol Use Disorder.

Alcohol use disorder is a pervasive and detrimental condition that involves changes in neuroplasticity and neurogenesis. Alcohol activates the neuroimmune system and alters the inflammatory status of the brain. Tumour necrosis factor (TNF) is a well characterised neuroimmune signal but its involvement in alcohol use disorder is unknown.

Reduced Inhibitory Inputs On Basolateral Amygdala Principal Neurons Following Long-Term Alcohol Consumption.

Recent studies have shown that manipulating basolateral amygdala (BLA) activity can affect alcohol consumption, particularly following chronic and/or long-term intake. Although the mechanisms underlying these effects remain unclear, the BLA is highly sensitive to emotional stimuli including stress and anxiety. Negative emotional states facilitate alcohol craving and relapse in patients with alcohol use disorders.

Assessment of nicotine release from nicotine-loaded chitosan nanoparticles dry powder inhaler formulations via locomotor activity of C57BL/6 mice.

Purpose: This study aimed to assess the activity of controlled release nicotine from dry powder inhaler formulation via locomotor activity of C57BL/6 mice.

Methods: To achieve this we built a nose-only inhalation device for pulmonary administration of nicotine to mice and determined the optimal operational parameters. We used the locomotor activity test to compare the effects of the inhaled nicotine hydrogen tartrate-loaded chitosan nanoparticles (NHT-CS) with NHT in C57BL/6 mice.

Pindolol Rescues Anxiety-Like Behavior and Neurogenic Maladaptations of Long-Term Binge Alcohol Intake in Mice.

Long-term binge alcohol consumption alters the signaling of numerous neurotransmitters in the brain including noradrenaline (NE) and serotonin (5-HT). Alterations in the signaling of these neuronal pathways result in dysfunctional emotional states like anxiety and depression which are typically seen during alcohol withdrawal. Interestingly, studies have demonstrated that the development of alcohol-induced negative affective states is linked to disrupted neurogenesis in the dentate gyrus (DG) region of the hippocampus in alcohol-dependent animals.

Pavlovian Olfactory Fear Conditioning: Its Neural Circuity and Importance for Understanding Clinical Fear-Based Disorders.

Odors have proven to be the most resilient trigger for memories of high emotional saliency. Fear associated olfactory memories pose a detrimental threat of potentially transforming into severe mental illness such as fear and anxiety-related disorders. Many studies have deliberated on auditory, visual and general contextual fear memory (CFC) processes; however, fewer studies have investigated mechanisms of olfactory fear memory.

Contextual Fear Conditioning Alter Microglia Number and Morphology in the Rat Dorsal Hippocampus.

Contextual fear conditioning is a Pavlovian conditioning paradigm capable of rapidly creating fear memories to contexts, such as rooms or chambers. Contextual fear conditioning protocols have long been utilized to evaluate how fear memories are consolidated, maintained, expressed, recalled, and extinguished within the brain. These studies have identified the lateral portion of the amygdala and the dorsal portion of the hippocampus as essential for contextual fear memory consolidation.

Axonal Non-segregation of the Vesicular Glutamate Transporter VGLUT3 Within Serotonergic Projections in the Mouse Forebrain.

A subpopulation of raphe 5-HT neurons expresses the vesicular glutamate transporter VGLUT3 with the co-release of glutamate and serotonin proposed to play a pivotal role in encoding reward- and anxiety-related behaviors. Serotonin axons are identifiable by immunolabeling of either serotonin (5-HT) or the plasma membrane 5-HT transporter (SERT), with SERT labeling demonstrated to be only partially overlapping with 5-HT staining. Studies investigating the colocalization or segregation of VGLUT3 within SERT or 5-HT immunolabeled boutons have led to inconsistent results.

The impact of sugar consumption on stress driven, emotional and addictive behaviors.

In 2016 the World Health Organization reported 39% of the world's adult population (over 18 y) was overweight, with western countries such as Australia and the United States of America at 64.5% and 67.9% respectively.

Microtopography of fear memory consolidation and extinction retrieval within prefrontal cortex and amygdala.

Rationale: The precise neural circuitry that encodes fear memory and its extinction within the brain are not yet fully understood. Fearful memories can be persistent, resistant to extinction, and associated with psychiatric disorders, especially post-traumatic stress disorder (PTSD). Here, we investigated the microtopography of neurons activated during the recall of an extinguished fear memory, as well as the influence of time on this microtopography.

Modulation of serotonin and noradrenaline in the BLA by pindolol reduces long-term ethanol intake.

Repeated cycles of binge-like alcohol consumption and abstinence change the activity of several neurotransmitter systems. Some of these changes are consolidated following prolonged alcohol use and are thought to play an important role in the development of dependence. We have previously shown that systemic administration of the dual beta-adrenergic antagonist and 5-HT partial agonist pindolol selectively reduces long-term but not short-term binge-like consumption of ethanol and alters excitatory postsynaptic currents in basolateral amygdala (BLA) principal neurons.

Sex Specific Alterations in α4*Nicotinic Receptor Expression in the Nucleus Accumbens.

: The mechanisms leading from traumatic stress to social, emotional and cognitive impairment and the development of mental illnesses are still undetermined and consequently there remains a critical need to develop therapies for preventing the adverse consequences of traumatic stress. Research indicates nicotinic acetylcholine receptors containing α4 subunits (α4*nAChRs) are both impacted by stress and capable of modulating the stress response. In this study, we investigated whether varenicline, a partial α4β2*nAChR agonist which reduces nicotine, alcohol and sucrose consumption, can reduce stress, a driving factor in substance use disorders.

5-HT1A receptor-dependent modulation of emotional and neurogenic deficits elicited by prolonged consumption of alcohol.

Repeated episodes of binge-like alcohol consumption produce anxiety, depression and various deleterious effects including alterations in neurogenesis. While the involvement of the serotonin receptor 1 A (5-HT) in the regulation of anxiety-like behavior and neurogenesis is well documented, its contribution to alcohol withdrawal-induced anxiety and alcohol-induced deficits in neurogenesis is less documented. Using the Drinking-In-the-Dark (DID) paradigm to model chronic long-term (12 weeks) binge-like voluntary alcohol consumption in mice, we show that the selective partial activation of 5-HT receptors by tandospirone (3 mg/kg) prevents alcohol withdrawal-induced anxiety in a battery of behavioral tests (marble burying, elevated-plus-maze, open-field), which is accompanied by a robust decrease in binge-like ethanol intake (1 and 3 mg/kg).