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Introduction: Adolescence is an important stage of maturation for various brain structures. It is during this time therefore that the brain may be more vulnerable to environmental factors such as diet that may influence mood and memory. Diets high in fat and sugar (termed a cafeteria diet) during adolescence have been shown to negatively impact upon cognitive performance, which may be reversed by switching to a standard diet during adulthood. Consumption of a cafeteria diet increases both peripheral and central levels of interleukin-1β (IL-1β), a pro-inflammatory cytokine which is also implicated in cognitive impairment during the ageing process. It is unknown whether adolescent exposure to a cafeteria diet potentiates the negative effects of IL-1β on cognitive function during adulthood. Methods: Male Sprague-Dawley rats consumed a cafeteria diet during adolescence after which time they received a lentivirus injection in the hippocampus to induce chronic low-grade overexpression of IL-1β. After viral integration, metabolic parameters, circulating and central pro-inflammatory cytokine levels, and cognitive behaviours were assessed. Results: Our data demonstrate that rats fed the cafeteria diet exhibit metabolic dysregulations in adulthood, which were concomitant with low-grade peripheral and central inflammation. Overexpression of hippocampal IL-1β in adulthood impaired spatial working memory. However, adolescent exposure to a cafeteria diet, combined with or without hippocampal IL-1β in adulthood did not induce any lasting cognitive deficits when the diet was replaced with a standard diet in adulthood. Discussion: These data demonstrate that cafeteria diet consumption during adolescence induces metabolic and inflammatory changes, but not behavioural changes in adulthood. [ABSTRACT FROM AUTHOR]

Over the past decade, there have been multiple studies into how bioretention systems perform in field, rather than laboratory, conditions, and into the quality of stormwater coming off urban catchments, yet in Australia standards, guidelines and software models have remained relatively static. A review of 15 field studies of bioretention systems, collectively covering 513 storm events, found a weighted average volumetric loss of 51% despite many of the systems having impermeable liners or were on clayey soils. The loss of water is about 17 times higher than is predicted by MUSIC when configured in accordance with standard guidelines. Some of the studies found increased pollutant concentrations in the effluent, with volumetric loss being the primary mechanism for pollutant load reduction. This research shows that bioretention systems perform more like sponges than filters and can have a potentially large impact on urban hydrology by reducing the volume and frequency of runoff, and helping attenuate minor flood events. Ultimately, this could lead to a better integration of the quality and quantity aspects of urban stormwater management. [ABSTRACT FROM AUTHOR]

Early life is a period of significant brain development when the brain is at its most plastic and vulnerable. Stressful episodes during this window of development have long-lasting effects on the central nervous system. Rodent maternal separation (MS) is a reliable model of early-life stress and induces alterations in both physiology and behaviour. Intriguingly, the gut microbiota of MS offspring differ from that of non-separated offspring, suggesting a mechanistic role for the microbiota–gut–brain axis. Hence, we tested whether dietary factors known to affect the gut microbiota alter the neurobehavioural effects of MS. The impact of consuming diet containing prebiotics polydextrose (PDX) and galactooligosaccharide (GOS) alone or in combination with live bacteria Lactobacillus rhamnosus GG (LGG) from weaning onwards in rats subjected to early-life MS was assessed. Adult offspring were assessed for anxiety-like behaviour in the open field test, spatial memory using the Morris water maze, and reactivity to restraint stress. Brains were examined via PCR for changes in mRNA gene expression. Here, we demonstrate that diets containing a combination of PDX/GOS and LGG attenuates the effects of early-life MS on anxiety-like behaviour and hippocampal-dependent learning with changes to hippocampal mRNA expression of genes related to stress circuitry, anxiety and learning. [ABSTRACT FROM AUTHOR]

Adolescence is a critical period for postnatal brain maturation and thus a time when environmental influences may affect cognitive processes in later life. Exercise during adulthood has been shown to increase hippocampal neurogenesis and enhance cognition. However, the impact of exercise initiated in adolescence on the brain and behavior in adulthood is not fully understood. The aim of this study was to compare the impact of voluntary exercise that is initiated during adolescence or early adulthood on cognitive performance in hippocampal‐dependent and ‐independent processes using both object‐based and touchscreen operant paradigms. Adult (8 week) and adolescent (4 week) male Sprague–Dawley rats had access to a running wheel (exercise) or were left undisturbed (sedentary control) for 4 weeks prior to behavioral testing and for the duration of the experiment. Results from touchscreen‐based tasks showed that reversal learning was enhanced by both adult and adolescent‐initiated exercise, while only exercise that began in adolescence induced a subtle but transient increase in performance on a location discrimination task. Spontaneous alternation in the Y‐maze was impaired following adolescent onset exercise, while object memory was unaffected by either adult or adolescent‐initiated exercise. Adolescent‐initiated exercise increased the number of hippocampal DCX cells, an indicator of neurogenesis. It also promoted the complexity of neurites on DCX cells, a key process for synaptic integration, to a greater degree than adult‐initiated exercise. Together the data here show that exercise during the adolescent period compared to adulthood differentially affects cognitive processes and the development of new hippocampal neurons in later life. [ABSTRACT FROM AUTHOR]

Abstract Adolescence is a critical period for postnatal brain maturation and a time during which there is increased susceptibility to developing emotional and cognitive-related disorders. Exercise during adulthood has been shown to increase hippocampal plasticity and enhance cognition. However, the impact of exercise initiated in adolescence, on brain and behaviour in adulthood is not yet fully explored or understood. The aim of this study was to compare the impact of voluntary exercise that was initiated either during adolescence or early adulthood on cognitive performance in hippocampal and amygdala-dependent fear conditioning tasks in adulthood. Adult (eight weeks old) and adolescent (four weeks old) male Sprague Dawley rats had access to a running wheel (exercise) or were left undisturbed (sedentary control) for seven weeks. Adult-initiated exercise enhanced both contextual and cued fear conditioning, while conversely, exercise that began in adolescence did not affect performance in these tasks. These behaviours were accompanied by differential expression of plasticity-related genes in the hippocampus and amygdala in adulthood. Specifically, adolescent-initiated exercise increased the expression of an array of plasticity related genes in the hippocampus including BDNF , synaptophysin , Creb , PSD-95 , Arc , TLX and DCX , while adult-initiated exercise did not affect hippocampal plasticity related genes. Together results show that exercise initiated during adolescence has a differential effect on hippocampal and amygdala-dependent behaviour and neuronal plasticity compared to when exercise was initiated in adulthood. These findings reinforce adolescence as a period during which environmental influences have a distinct impact on neuronal plasticity and cognition. This article is part of the Special Issue entitled "Neurobiology of Environmental Enrichment". Highlights • Adult-initiated exercise enhanced fear learning. • Adolescent-initiated did not affect fear learning in adulthood. • Adolescent-initiated exercise enhanced hippocampal neural plasticity. [ABSTRACT FROM AUTHOR]

Birth by Caesarean (C)-section impacts early gut microbiota colonization and is associated with an increased risk of developing immune and metabolic disorders. Moreover, alterations of the microbiome have been shown to affect neurodevelopmental trajectories. However, the long-term effects of C-section on neurobehavioral processes remain unknown. Here, we demonstrated that birth by C-section results in marked but transient changes in microbiome composition in the mouse, in particular, the abundance of Bifidobacterium spp. was depleted in early life. Mice born by C-section had enduring social, cognitive, and anxiety deficits in early life and adulthood. Interestingly, we found that these specific behavioral alterations induced by the mode of birth were also partially corrected by co-housing with vaginally born mice. Finally, we showed that supplementation from birth with a Bifidobacterium breve strain, or with a dietary prebiotic mixture that stimulates the growth of bifidobacteria, reverses selective behavioral alterations in C-section mice. Taken together, our data link the gut microbiota to behavioral alterations in C-section-born mice and suggest the possibility of developing adjunctive microbiota-targeted therapies that may help to avert long-term negative consequences on behavior associated with C-section birth mode. • C-section leads to changes in Bifidobacterium spp. abundance in early life • Mice born by C-section have behavioral deficits throughout their lifespan • Co-housing C-section-born mice with vaginally born mice corrects social deficits • B. breve or a dietary prebiotic mixture improves behavior in C-section mice Recent evidence points to an important role for the microbiome in regulating brain function and behavior. Here, Morais et al. show that birth by C-section results in a different pattern of microbiota colonization with long-term behavioral consequences in the mouse. Targeting the gut microbiota reverses social behavioral effects of C-section. [ABSTRACT FROM AUTHOR]

Visceral hypersensitivity is a hallmark of many functional and stress-related gastrointestinal disorders, and there is growing evidence that the gut microbiota may play a role in its pathophysiology. It has previously been shown that early life stress-induced visceral sensitivity is reduced by various probiotic strains of bacteria (including Lactobacillus rhamnosus GG (LGG)) alone or in combination with prebiotic fibres in rat models. However, the exact mechanisms underpinning such effects remain unresolved. Here, we investigated if soluble mediators derived from LGG can mimic the bacteria's effects on visceral hypersensitivity and the microbiota-gut-brain axis. Rats were exposed to maternal separation (MS) from postnatal days 2-12. From weaning onwards both non-separated (NS) and MS offspring were provided drinking water with or without supplementation of standardized preparations of the LGG soluble mediators (LSM). Our results show that MS led to increased visceral sensitivity and exaggerated corticosterone plasma levels following restraint stress in adulthood, and both of these effects were ameliorated through LSM supplementation. Differential regulation of various genes in the spinal cord of MS versus NS rats was observed, 41 of which were reversed by LSM supplementation. At the microbiota composition level MS led to changes in beta diversity and abundance of specific bacteria including parabacteroides , which were ameliorated by LSM. These findings support probiotic soluble mediators as potential interventions in the reduction of symptoms of visceral hypersensitivity., Competing Interests: The authors declare that there are no competing interests associated with the manuscript., (© 2020 The Author(s).)

Microglia are an essential component of the neurogenic niche in the adult hippocampus and are involved in the control of neural precursor cell (NPC) proliferation, differentiation and the survival and integration of newborn neurons in hippocampal circuitry. Microglial and neuronal cross-talk is mediated in part by the chemokine fractalkine/chemokine (C-X3-C motif) ligand 1 (CX3CL1) released from neurons, and its receptor CX3C chemokine receptor 1 (CX3CR1) which is expressed on microglia. A disruption in this pathway has been associated with impaired neurogenesis yet the specific molecular mechanisms by which this interaction occurs remain unclear. The orphan nuclear receptor TLX (Nr2e1; homologue of the Drosophila tailless gene) is a key regulator of hippocampal neurogenesis, and we have shown that in its absence microglia exhibit a pro-inflammatory activation phenotype. However, it is unclear whether a disturbance in CX3CL1/CX3CR1 communication mediates an impairment in TLX-related pathways which may have subsequent effects on neurogenesis. To this end, we assessed miRNA expression of up- and down-stream signalling molecules of TLX in the hippocampus of mice lacking CX3CR1. Our results demonstrate that a lack of CX3CR1 is associated with altered expression of TLX and its downstream targets in the hippocampus without significantly affecting upstream regulators of TLX. Thus, TLX may be a potential participant in neural stem cell (NSC)-microglial cross-talk and may be an important target in understanding inflammatory-associated impairments in neurogenesis., Competing Interests: The authors declare that there are no competing interests associated with the manuscript., (© 2019 The Author(s).)

Social behaviour is regulated by activity of host-associated microbiota across multiple species. However, the molecular mechanisms mediating this relationship remain elusive. We therefore determined the dynamic, stimulus-dependent transcriptional regulation of germ-free (GF) and GF mice colonised post weaning (exGF) in the amygdala, a brain region critically involved in regulating social interaction. In GF mice the dynamic response seen in controls was attenuated and replaced by a marked increase in expression of splicing factors and alternative exon usage in GF mice upon stimulation, which was even more pronounced in exGF mice. In conclusion, we demonstrate a molecular basis for how the host microbiome is crucial for a normal behavioural response during social interaction. Our data further suggest that social behaviour is correlated with the gene-expression response in the amygdala, established during neurodevelopment as a result of host-microbe interactions. Our findings may help toward understanding neurodevelopmental events leading to social behaviour dysregulation, such as those found in autism spectrum disorders (ASDs)., Competing Interests: RS, GM, FR, AH, TB No competing interests declared, FS principal investigator in the APC Microbiome Institute, University College Cork, GC faculty member or funded investigator of the APC Microbiome Institute. The APC Microbiome Institute has conducted research funded by Pfizer, GlaxoSmithKline, Proctor & Gamble, Mead Johnson, Suntory Wellness, and Cremo, MC Marcus J Claesson: faculty member or funded investigator of the APC Microbiome Institute. The APC Microbiome Institute has conducted research funded by Pfizer, GlaxoSmithKline, Proctor & Gamble, Mead Johnson, Suntory Wellness, and Cremo, TD principal investigator in the APC Microbiome Institute, University College Cork. Has been an invited speaker at meetings organized by Servier, Lundbeck, Janssen, and AstraZeneca. JC principal investigator in the APC Microbiome Institute, University College Cork. Has been an invited speaker at meetings organized by Mead Johnson, Yakult, Alkermes, and Janssen., (© 2018, Stilling et al.)

Introduction: Anxiety disorders are the most frequently diagnosed psychiatric conditions, negatively affecting quality of life and creating a significant economic burden. These complex disorders are extremely difficult to treat, and there is a great need for novel therapeutics with greater efficacy and minimal adverse side effects., Areas Covered: In this review, the authors describe the role that microribonucleic acids (microRNA or miRNA) play in the development of anxiety disorders and their potential to serve as biomarkers of disease as well as targets for pharmacological treatment. Furthermore, the authors discuss the current state of miRNA research, including both preclinical and clinical studies of anxiety disorders., Expert Opinion: There is mounting evidence that circulating miRNA may serve as biomarkers of disease and play a role in the development of disease, including psychiatric conditions such as anxiety disorders. Great strides have been made in cancer research, with miRNA-based therapies already in use in clinical studies. However, the use of miRNA for the treatment of neurological disorders, and psychiatric disorders in particular, is still in its nascent stage. The development of safe compounds that are able to cross the blood-brain barrier and target specific cell populations, which are relevant to anxiety-related neurocircuitry, is paramount for the emergence of novel, efficacious miRNA-based therapies in clinical settings.