Cerebellar Purkinje cell vulnerability to prenatal nicotine exposure in sudden unexplained perinatal death

Lavezzi, Anna Maria; Corna, Melissa F.; Repetti, Maria L.; Matturri, Luigi

doi:10.5114/fn.2013.39718

Cited by 21 publications

(24 citation statements)

References 42 publications

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“…Our previous studies have reported on an array of important side effects of nicotine exposure on the developmental process of the different brainstem centers essential for life (Lavezzi, Ottaviani, Mingrone, et al., 2005; Lavezzi, Ottaviani, Matturri, 2005; Lavezzi et al., 2007; Lavezzi et al., 2013; Lavezzi, Ferrero, et al., 2016). The findings of our study add new insights to this field and highlight the fact that the altered expression of nAChR, also limited to CC, puts fetuses exposed to maternal cigarette smoking in utero, at higher risk of SIDS or SIUDS.…”

Section: Discussionmentioning

confidence: 99%

Nicotinic Receptor Abnormalities in the Cerebellar Cortex of Sudden Unexplained Fetal and Infant Death Victims—Possible Correlation With Maternal Smoking

et al. 2017

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Nicotinic acetylcholine receptors (nAChRs) are cationic channels of the neuronal cell membrane, differentially expressed in the central nervous system which, when activated by endogenous acetylcholine or exogenous nicotine, are able to enhance cholinergic transmission. The aim of this study was to investigate in human perinatal age the immunohistochemical expression of the α7-nAChR subtype, given its involvement in neuronal differentiation and its significant vulnerability to the toxic effects of nicotine. Thirty fetuses (with a gestational age between 25 and 40 weeks) and 35 infants (1–6 months old), suddenly died of known (controls) and unknown causes (unexplained deaths), with smoking and nonsmoking mothers, were included in this study. A negative or low immunoexpression of α7-nAChRs, indicative of their inactivation, was observed in the granular layers of the cerebellar cortex in 66% of the sudden unexplained perinatal deaths and 11% of the controls. A high correlation was also observed between these findings and maternal smoking. Apart from the well-known adverse effects of nicotine exposure during pregnancy, it may also cause significant alterations in cerebellar cholinergic transmission in areas of the brain involved in vital functions. These events may give us insights into the pathogenetic mechanisms leading to sudden unexplained fetal and infant death.

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Section: Discussionmentioning

confidence: 99%

Nicotinic Receptor Abnormalities in the Cerebellar Cortex of Sudden Unexplained Fetal and Infant Death Victims—Possible Correlation With Maternal Smoking

et al. 2017

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“…The high metabolic rate may contribute to cerebellar vulnerability to mitochondrial dysfunction, RNA toxicity, environmental insults, and comorbidity, and thus increase its risk of atrophy during aging. Indeed, intranuclear inclusions have been observed in dentate nuclei, reflecting the effect of RNA toxicity; and mitochondrial dysfunction (Ross-Inta et al , 2010, Napoli et al , 2016) and high prevalence of hypertension, substance abuse and alcohol abuse have been reported in premutation carriers (Dorn et al , 1994, Kogan et al , 2008, Polussa et al , 2014), which may play a role in cerebellar atrophy during aging (Miquel et al , 2009, Lavezzi et al , 2013, Miquel et al , 2016). Additional studies are needed to uncover the mechanisms causing cerebellar underdevelopment often with specific developmental problems and late neurodegeneration due to FXTAS progression.…”

Section: Discussionmentioning

confidence: 99%

Abnormal trajectories in cerebellum and brainstem volumes in carriers of the fragile X premutation

Wang

Hessl

Hagerman

et al. 2017

Neurobiology of Aging

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Fragile X-associated tremor/ataxia syndrome (FXTAS) is a late-onset neurodegenerative disorder typically affecting male premutation carriers with 55–200 CGG repeat expansions in the FMR1 gene after age 50. The aim of this study was to examine whether cerebellar and brainstem changes emerge during development or aging in late life. We retrospectively analyzed MRI scans from 322 males (age 8–81 years). Volume changes in the cerebellum and brainstem were contrasted with those in the ventricles and whole brain. Compared to the controls, premutation carriers without FXTAS showed significantly accelerated volume decrease in the cerebellum and whole brain, flatter inverted U-shaped trajectory of the brainstem, and larger ventricles. Compared to both older controls and premutation carriers without FXTAS, carriers with FXTAS exhibited significant volume decrease in the cerebellum and whole brain and accelerated volume decrease in the brainstem. We therefore conclude that cerebellar and brainstem volumes were likely affected during both development and progression of neurodegeneration in premutation carriers, suggesting that interventions may need to start early in adulthood to be most effective.

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“…This study was, however, limited to the brainstem examination. Therefore, here our aim was to extend our previous investigation by focusing, in the same cases, on the BDNF expression in the cerebellum and, above all, in cerebellar cortex, which we have already shown to be particularly susceptible to developmental abnormalities in sudden perinatal death victims, especially in association with risk factors such as exposure to cigarette smoke (Lavezzi et al, 2006a; Lavezzi et al, 2013; Lavezzi et al, 2006b; Lavezzi et al, 2007; Lavezzi et al, 2016).…”

Section: Introductionmentioning

confidence: 97%

Pathobiological expression of the brain‐derived neurotrophic factor (BDNF) in cerebellar cortex of sudden fetal and infant death victims

Lavezzi

Ferrero

Lattuada

et al. 2017

Intl J of Devlp Neuroscience

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Brain-derived neurotrophic factor (BDNF), a neurotrophin of the central nervous system, is able to regulate neuronal differentiation and modulate synaptic plasticity, being particularly involved in the development of the cerebellar cortical structure. The main aim of this study was to delineate, by immunohistochemistry, the BDNF expression in human cerebellar cortex of victims of fetal and infant death. The study was performed on a total of 45 cases, aged between 25 gestational weeks and 6 postnatal months, including 29 victims of sudden fetal and infant death and 16 age-matched subjects who died of known causes (Controls). We observed, in sudden death groups compared with Controls, a significantly higher incidence of defective BDNF expression in granule layers of the cerebellar cortex, which was particularly evident in the posterior lobule, a region that participates in respiratory control. These results were related to maternal smoking, allowing to speculate that nicotine, in addition to the well-known damages, can exert adverse effects during cerebellar cortex development, in particular in hindering the BDNF expression in the posterior lobule. This implies modifications of synaptic transmission in the respiratory circuits, with obvious deleterious consequences on survival.

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Cerebellar Purkinje cell vulnerability to prenatal nicotine exposure in sudden unexplained perinatal death

Abstract: A b s t r a c tThe present study was aimed at supplementing our previous investigations on the morphological

Cited by 21 publications

References 42 publications

Nicotinic Receptor Abnormalities in the Cerebellar Cortex of Sudden Unexplained Fetal and Infant Death Victims—Possible Correlation With Maternal Smoking

Nicotinic Receptor Abnormalities in the Cerebellar Cortex of Sudden Unexplained Fetal and Infant Death Victims—Possible Correlation With Maternal Smoking

Abnormal trajectories in cerebellum and brainstem volumes in carriers of the fragile X premutation

Pathobiological expression of the brain‐derived neurotrophic factor (BDNF) in cerebellar cortex of sudden fetal and infant death victims

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