- Quality of life after paediatric ischaemic stroke. [Journal Article]
- DMDev Med Child Neurol 2016 Oct 21
- CONCLUSIONS: Neurological and cognitive impairments after paediatric arterial ischaemic stroke negatively influence QoL. Children with motor and neurological problems, as well as those with combined motor, cognitive, and attention problems, are at higher risk for low QoL.
- ACCORDION MIND: results of the observational extension of the ACCORD MIND randomised trial. [Journal Article]
- DDiabetologia 2016 Oct 20
- CONCLUSIONS: The ACCORD interventions did not result in long-term beneficial or adverse effects on cognitive or brain MRI outcomes at approximately 80 months follow-up. Loss of separation in therapeutic targets between treatment arms and loss to follow-up may have contributed to the lack of detectable long-term effects.
- Behavioral Neuroadaptation to Alcohol: From Glucocorticoids to Histone Acetylation. [Review]
- FPFront Psychiatry 2016; 7:165
- A prime mechanism that contributes to the development and maintenance of alcoholism is the dysregulation of the hypothalamic-pituitary-adrenal axis activity and the release of glucocorticoids (cortis...
A prime mechanism that contributes to the development and maintenance of alcoholism is the dysregulation of the hypothalamic-pituitary-adrenal axis activity and the release of glucocorticoids (cortisol in humans and primates, corticosterone in rodents) from the adrenal glands. In the brain, sustained, local elevation of glucocorticoid concentration even long after cessation of chronic alcohol consumption compromises functional integrity of a circuit, including the prefrontal cortex (PFC), the hippocampus (HPC), and the amygdala (AMG). These structures are implicated in learning and memory processes as well as in orchestrating neuroadaptive responses to stress and anxiety responses. Thus, potentiation of anxiety-related neuroadaptation by alcohol is characterized by an abnormally AMG hyperactivity coupled with a hypofunction of the PFC and the HPC. This review describes research on molecular and epigenetic mechanisms by which alcohol causes distinct region-specific adaptive changes in gene expression patterns and ultimately leads to a variety of cognitive and behavioral impairments on prefrontal- and hippocampal-based tasks. Alcohol-induced neuroadaptations involve the dysregulation of numerous signaling cascades, leading to long-term changes in transcriptional profiles of genes, through the actions of transcription factors such as [cAMP response element-binding protein (CREB)] and chromatin remodeling due to posttranslational modifications of histone proteins. We describe the role of prefrontal-HPC-AMG circuit in mediating the effects of acute and chronic alcohol on learning and memory, and region-specific molecular and epigenetic mechanisms involved in this process. This review first discusses the importance of brain region-specific dysregulation of glucocorticoid concentration in the development of alcohol dependence and describes how persistently increased glucocorticoid levels in PFC may be involved in mediating working memory impairments and neuroadaptive changes during withdrawal from chronic alcohol intake. It then highlights the role of cAMP-PKA-CREB signaling cascade and histone acetylation within the PFC and limbic structures in alcohol-induced anxiety and behavioral impairments, and how an understanding of functional alterations of these pathways might lead to better treatments for neuropsychiatric disorders.
- Multivariate synaptic and behavioral profiling reveals new developmental endophenotypes in the prefrontal cortex. [Journal Article]
- SRSci Rep 2016 Oct 21; 6:35504
- The postnatal maturation of the prefrontal cortex (PFC) represents a period of increased vulnerability to risk factors and emergence of neuropsychiatric disorders. To disambiguate the pathophysiologi...
The postnatal maturation of the prefrontal cortex (PFC) represents a period of increased vulnerability to risk factors and emergence of neuropsychiatric disorders. To disambiguate the pathophysiological mechanisms contributing to these disorders, we revisited the endophenotype approach from a developmental viewpoint. The extracellular matrix protein reelin which contributes to cellular and network plasticity, is a risk factor for several psychiatric diseases. We mapped the aggregate effect of the RELN risk allele on postnatal development of PFC functions by cross-sectional synaptic and behavioral analysis of reelin-haploinsufficient mice. Multivariate analysis of bootstrapped datasets revealed subgroups of phenotypic traits specific to each maturational epoch. The preeminence of synaptic AMPA/NMDA receptor content to pre-weaning and juvenile endophenotypes shifts to long-term potentiation and memory renewal during adolescence followed by NMDA-GluN2B synaptic content in adulthood. Strikingly, multivariate analysis shows that pharmacological rehabilitation of reelin haploinsufficient dysfunctions is mediated through induction of new endophenotypes rather than reversion to wild-type traits. By delineating previously unknown developmental endophenotypic sequences, we conceived a promising general strategy to disambiguate the molecular underpinnings of complex psychiatric disorders and for the rational design of pharmacotherapies in these disorders.
- Circadian rhythms have significant effects on leaf-to-canopy scale gas exchange under field conditions. [Journal Article]
- GGigascience 2016 Oct 20; 5(1):43
- CONCLUSIONS: Our results show that circadian controls affect diurnal CO2 and H2O flux patterns in entire canopies in field-like conditions, and its consideration significantly improves model performance. Circadian controls act as a 'memory' of the past conditions experienced by the plant, which synchronizes metabolism across entire plant canopies.
- Ameliorative effects of egg white hydrolysate on recognition memory impairments associated with chronic exposure to low mercury concentration. [Journal Article]
- NINeurochem Int 2016 Oct 11; 101:30-37
- The study aimed to investigate whether the Egg White Hydrolysate (EWH) is able to prevent the recognition memory disorders associated with long-term Hg exposure in rats. For this, male Wistar rats we...
The study aimed to investigate whether the Egg White Hydrolysate (EWH) is able to prevent the recognition memory disorders associated with long-term Hg exposure in rats. For this, male Wistar rats were treated for 60 days with: a) Untreated: saline solution (i.m.); b) Hydrolysate: EWH (1 g/kg/day, gavage); c) Mercury: HgCl2 (1st dose 4.6 μg/kg, subsequent doses 0.07 μg/kg/day, i.m.); d) Hydrolysate-Mercury. Object recognition memory test was performed to verify Short (STM) and Long-Term Memory (LTM) and Open Field, Plus Maze and Tail Flick tests were performed as control for behavioural experiments. Reactive Oxygen Species (ROS) in the hippocampus were determined by the dichlorofluorescein diacetate (DCFH-DA) method, malondialdehyde (MDA) levels by TBARS, antioxidant power by FRAP assay and total Hg concentration by atomic fluorescence spectrometry. We confirm that the STM and LTM were impaired in adult rats exposed to Hg at low concentrations, which may be related to the increased metal deposition, ROS production and subsequent oxidative damage in the hippocampus. In addition, we demonstrated for the first time that EWH treatment is able to prevent memory impairment induced by Hg exposure, reducing Hg content and ROS production in the hippocampus. In conclusion, EWH prevents memory impairments induced by chronic exposure to low doses of Hg. These findings may represent a good public health strategy since they indicate that EWH is a promising candidate as a new natural therapy for heavy metal intoxication.
- Qualitatively different memory states in Lymnaea as shown by differential responses to propranolol. [Journal Article]
- NLNeurobiol Learn Mem 2016 Sep 23; 136:63-73
- Mixed results with the synthetic β-adrenergic receptor blocker, propranolol, have been reported in human populations with regards to its therapeutic efficacy for PTSD treatments targeting the memory ...
Mixed results with the synthetic β-adrenergic receptor blocker, propranolol, have been reported in human populations with regards to its therapeutic efficacy for PTSD treatments targeting the memory reconsolidation process. Stress alters the ability to form and maintain memory, but whether the causal neuronal mechanisms underling memory formation in PTSD are similar to normal memory is not clear. Here, we use Lymnaea to study the effects of combinations of stressors on the quality of the formed memory state. We show reactivation dependent pharmacologic disruption of reconsolidation using propranolol in Lymnaea; specifically, we show that only certain memories created under conditions of a combination of stressors are susceptible to disruption. Our data suggest that phenotypically similar memories may be molecularly diverse, depending on the conditions under which they are formed. Applied to human PTSD, this could account for the mixed results in the literature on disrupting reconsolidation with propranolol.
- Mechanisms underlying long-term fear memory formation from a metaplastic neuronal state. [Journal Article]
- NLNeurobiol Learn Mem 2016 Sep 19; 136:47-53
- We previously showed that a single weak fear conditioning trial, that does not produce a long-term fear memory (LTM), appeared to prime memory formation such that when a second trial followed within ...
We previously showed that a single weak fear conditioning trial, that does not produce a long-term fear memory (LTM), appeared to prime memory formation such that when a second trial followed within a circumscribed time window a robust and long-lasting fear memory was formed. We also showed that this priming effect could be blocked if we interfered with protein kinase A (PKA) signaling in the amygdala during the first conditioning trial. The goals of the current study were to determine if LTM formation after the second trial depends on PKA signaling in the amygdala and to characterize the underlying memory processes engaged during the second trial that allows for LTM formation. Our interpretation of the original findings is that the second conditioning trial triggers LTM from a metaplastic state that is engaged by the first conditioning trial. However, it is also possible that the second conditioning trial acts as a reminder of the first and engages a reconsolidation-like process. Several experiments were conducted to distinguish between these two possibilities. We show that interfering with PKA signaling during the second conditioning trial disrupts memory formation. However, if a third trial follows the second or if the second trial was presented without shock, the PKA inhibitor was no longer effective. Our findings demonstrate that the induction of fear memory from a metaplastic state involves new learning that is distinct from retrieval-dependent updating of memories.
- Impaired function of α2-containing nicotinic acetylcholine receptors on oriens-lacunosum moleculare cells causes hippocampus-dependent memory impairments. [Journal Article]
- NLNeurobiol Learn Mem 2016 Sep 19; 136:13-20
- Children of mothers who smoked during pregnancy are at significantly greater risk for cognitive impairments including memory deficits, but the mechanisms underlying this effect remain to be understoo...
Children of mothers who smoked during pregnancy are at significantly greater risk for cognitive impairments including memory deficits, but the mechanisms underlying this effect remain to be understood. In rodent models of smoking during pregnancy, early postnatal nicotine exposure results in impaired long-term hippocampus-dependent memory, functional loss of α2-containing nicotinic acetylcholine receptors (α2(∗) nAChRs) in oriens-lacunosum moleculare (OLM) cells, increased CA1 network excitation, and unexpected facilitation of long-term potentiation (LTP) at Schaffer collateral-CA1 synapses. Here we demonstrate that α2 knockout mice show the same pattern of memory impairment as previously observed in wild-type mice exposed to early postnatal nicotine. However, α2 knockout mice and α2 knockout mice exposed to early postnatal nicotine did not share all of the anomalies in hippocampal function observed in wild-type mice treated with nicotine during development. Unlike nicotine-treated wild-type mice, α2 knockout mice and nicotine-exposed α2 knockout mice did not demonstrate increased CA1 network excitation following Schaffer collateral stimulation and facilitated LTP, indicating that the effects are likely adaptive changes caused by activation of α2(∗) nAChRs during nicotine exposure and are unlikely related to the associated memory impairment. Thus, the functional loss of α2(∗) nAChRs in OLM cells likely plays a critical role in mediating this developmental-nicotine-induced hippocampal memory deficit.
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- Extending the duration of long-term memories: Interactions between environmental darkness and retinoid signaling. [Journal Article]
- NLNeurobiol Learn Mem 2016 Sep 16; 136:34-46
- Retinoid signaling plays an important role in hippocampal-dependent vertebrate memories. However, we have previously demonstrated that retinoids are also involved in the formation of long-term implic...
Retinoid signaling plays an important role in hippocampal-dependent vertebrate memories. However, we have previously demonstrated that retinoids are also involved in the formation of long-term implicit memory following operant conditioning of the invertebrate mollusc Lymnaea stagnalis. Furthermore, we have discovered an interaction between environmental light/dark conditions and retinoid signaling and the ability of both to convert intermediate-term memory into long-term memory. In this study, we extend these findings to show that retinoid receptor agonists and environmental darkness can both also extend the duration of long-term memory. Interestingly, exposure to constant environmental darkness significantly increased the expression of retinoid receptors in the adult central nervous system, as well as induced specific changes in a key neuron mediating the conditioned behaviour. These studies not only shed more light on how retinoids influence memory formation, but also further link environmental light conditions to the retinoid signaling pathway.