Effects of Prenatal Electronic Cigarette Exposure On Foetal Development: a Review of the Literature.

Since their market launch in 2007, e-cigarettes gained popularity and were considered a relatively safe alternative to traditional cigarettes. Pregnant women and women of childbearing age in particular are increasingly turning to e-cigarettes. Little is known about the effects of prenatal exposure on the affected foetus. This paper aims to provide an overview of the current research on the effects of prenatal e-cigarette exposure on the foetus. Since studies in humans are lacking to date, this review refers only to animal and in vitro analyses. The PubMed and Web of Science databases were used for an extensive literature search. The search yielded N = 17 significant research papers. Possible sequelae resulting from prenatal exposure to traditional cigarettes were also seen in prenatal exposure to e-cigarettes. Prenatal e-cigarette exposure was found to be associated with increased DNA methylation overall, resulting in lower gene expression. This could adversely impact the development of affected children, especially in case of those genes relevant to their development. In mice, for example, this greatly reduced the cell vitality of neural and stem cells and increased cell death. Further, prenatal exposure to e-cigarettes resulted in numerous developmental disorders, such as malformations of facial morphology and lower birth weight. Moreover, in animal models the animals suffered from a deterioration of their short-term memory. Activity and cognitive flexibility increased, while anxiety behaviour decreased. It is clear that more research and especially studies of humans are needed on this issue. In addition, there is a need for more intense education of prenatal care professionals as well as women of childbearing age and during pregnancy.

Systematic review showed that low and moderate prenatal alcohol and nicotine exposure affected early child development.

AIM: We systematically reviewed the literature on the influence of low and moderate amounts of prenatal alcohol and nicotine exposure on early child development. This paper also suggests possible directions for future research in order to tackle the controversial findings identified. METHODS: The PubMed and Web of Science electronic databases were searched together with the reference lists of the selected papers. Empirical studies were included if they focused on the effects of low or moderate exposure, reported outcomes on child development within the first 2 years of life and were published in English between January 2009 and December 2019. The eligibility of the included studies was based on three authors reading the full text. RESULTS: The final sample comprised 17 papers. Of these, 13 focused on the effects of prenatal alcohol exposure and they reported decreased sensory sensibility, smaller body sizes and increased cognitive capacities. The other four looked at prenatal nicotine exposure, and they primarily found impairments in children's orienting, communication and motor skills. CONCLUSION: Any amount of prenatal alcohol and nicotine exposure appeared to risk healthy child development. There were many reasons for consumption and numerous effects on the child, but representative data from interdisciplinary research were missing.

Dissociating frontal and temporal correlates of phonological and semantic fluency in a large sample of left hemisphere stroke patients.

Previous lesion studies suggest that semantic and phonological fluency are differentially subserved by distinct brain regions in the left temporal and the left frontal cortex, respectively. However, as of yet, this often implied double dissociation has not been explicitly investigated due to mainly two reasons: (i) the lack of sufficiently large samples of brain-lesioned patients that underwent assessment of the two fluency variants and (ii) the lack of tools to assess interactions in factorial analyses of non-normally distributed behavioral data. In addition, previous studies did not control for task resource artifacts potentially introduced by the generally higher task difficulty of phonological compared to semantic fluency. We addressed these issues by task-difficulty adjusted assessment of semantic and phonological fluency in 85 chronic patients with ischemic stroke of the left middle cerebral artery. For classical region-based lesion-behavior mapping patients were grouped with respect to their primary lesion location. Building on the extension of the non-parametric Brunner-Munzel rank-order test to multi-factorial designs, ANOVA-type analyses revealed a significant two-way interaction for cue type (semantic vs. phonological) by lesion location (left temporal vs. left frontal vs. other as stroke control group). Subsequent contrast analyses further confirmed the proposed double dissociation by demonstrating that (i) compared to stroke controls, left temporal lesions led to significant impairments in semantic but not in phonological fluency, whereas left frontal lesions led to significant impairments in phonological but not in semantic fluency, and that (ii) patients with frontal lesions showed significantly poorer performance in phonological than in semantic fluency, whereas patients with temporal lesions showed significantly poorer performance in semantic than in phonological fluency. The anatomical specificity of these findings was further assessed in voxel-based lesion-behavior mapping analyses using the multi-factorial extension of the Brunner-Munzel test. Voxel-wise ANOVA-type analyses identified circumscribed parts of left inferior frontal gyrus and left superior and middle temporal gyrus that significantly double-dissociated with respect to their differential contribution to phonological and semantic fluency, respectively. Furthermore, a main effect of lesion with significant impairments in both fluency types was found in left inferior frontal regions adjacent to but not overlapping with those showing the differential effect for phonological fluency. The present study hence not only provides first explicit evidence for the anatomical double dissociation in verbal fluency at the group level but also clearly underlines that its formulation constitutes an oversimplification as parts of left frontal cortex appear to contribute to both semantic and phonological fluency.

Targeting Voltage-Dependent Calcium Channels with Pregabalin Exerts a Direct Neuroprotective Effect in an Animal Model of Multiple Sclerosis.

BACKGROUND/AIMS: Multiple sclerosis (MS) is a prototypical autoimmune central nervous system (CNS) disease. Particularly progressive forms of MS (PMS) show significant neuroaxonal damage as consequence of demyelination and neuronal hyperexcitation. Immuno-modulatory treatment strategies are beneficial in relapsing MS (RMS), but mostly fail in PMS. Pregabalin (Lyrica®) is prescribed to MS patients to treat neuropathic pain. Mechanistically, it targets voltage-dependent Ca2+ channels and reduces harmful neuronal hyperexcitation in mouse epilepsy models. Studies suggest that GABA analogues like pregabalin exert neuroprotective effects in animal models of ischemia and trauma. METHODS: We tested the impact of pregabalin in a mouse model of MS (experimental autoimmune encephalomyelitis, EAE) and performed histological and immunological evaluations as well as intravital two-photon-microscopy of brainstem EAE lesions. RESULTS: Both prophylactic and therapeutic treatments ameliorated the clinical symptoms of EAE and reduced immune cell infiltration into the CNS. On neuronal level, pregabalin reduced long-term potentiation in hippocampal brain slices indicating an impact on mechanisms of learning and memory. In contrast, T cells, microglia and brain endothelial cells were unaffected by pregabalin. However, we found a direct impact of pregabalin on neurons during CNS inflammation as it reversed the pathological elevation of neuronal intracellular Ca2+ levels in EAE lesions. CONCLUSION: The presented data suggest that pregabalin primarily acts on neuronal Ca2+ channel trafficking thereby reducing Ca2+-mediated cytotoxicity and neuronal damage in an animal model of MS. Future clinical trials need to assess the benefit for neuronal survival by expanding the indication for pregabalin administration to MS patients in further disease phases.

Are semantic and phonological fluency based on the same or distinct sets of cognitive processes? Insights from factor analyses in healthy adults and stroke patients.

Verbal fluency for semantic categories and phonological letters is frequently applied to studies of language and executive functions. Despite its popularity, it is still debated whether measures of semantic and phonological fluency reflect the same or distinct sets of cognitive processes. Word generation in the two task variants is believed to involve different types of search processes. Findings from the lesion and neuroimaging literature further suggest a stronger reliance of phonological and semantic fluency on frontal and temporal brain areas, respectively. This evidence for differential cognitive and neural contributions is, however, strongly challenged by findings from factor analyses, which have consistently yielded only one explanatory factor. As all previous factor-analytical approaches were based on very small item sets, this apparent discrepancy may be due to methodological limitations. In this study, we therefore applied a German version of the verbal fluency task with 8 semantic (i.e. categories) and 8 phonological items (i.e. letters). An exploratory factor analysis with oblique rotation in N=69 healthy young adults indeed revealed a two-factor solution with markedly different loadings for semantic and phonological items. This pattern was corroborated by a confirmatory factor analysis in a sample of N=174 stroke patients. As results from both samples also revealed a substantial portion of common variance between the semantic and phonological factor, the present data further demonstrate that semantic and phonological verbal fluency are based on clearly distinct but also on shared sets of cognitive processes.