Long-lasting teratogenic effects of nicotine on cognition: Gender specificity and role of AMPA receptor function

Vaglenova, Julia; Parameshwaran, Kodeeswaran; Suppiramaniam, Vishnu; Breese, Charles R.; Pandiella, Noemi; Birru, Sandjay

doi:10.1016/j.nlm.2008.06.009

Cited by 62 publications

(75 citation statements)

References 57 publications

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“…In a previous report, we demonstrated that in 2-month-old rats prenatally exposed to nicotine, the AMPA receptor-mediated synaptic currents were significantly reduced, suggesting long-lasting impairment in excitatory synaptic physiology [17]. Importantly, disruptions in the hippocampal glutamatergic system are attributed to mood disorders like anxiety and depression [18,19] and several animal studies provided accounts on neurobehavioral outcomes of prenatal nicotine exposure [17,20,21]. However, there is a lack of understanding of the possible molecular mechanisms contributing to these behavioral outcomes and if they are specifically related to hippocampus and its major excitatory neurotransmitter system.…”

Section: Introductionmentioning

confidence: 78%

“…This enhancement of excitatory transmission is mainly achieved by recruitment of additional a-amino-3-hydroxyl-5-methyl-4-isoxazole-propionic acid (AMPA) receptors to the postsynaptic membranes. In a previous report, we demonstrated that in 2-month-old rats prenatally exposed to nicotine, the AMPA receptor-mediated synaptic currents were significantly reduced, suggesting long-lasting impairment in excitatory synaptic physiology [17]. Importantly, disruptions in the hippocampal glutamatergic system are attributed to mood disorders like anxiety and depression [18,19] and several animal studies provided accounts on neurobehavioral outcomes of prenatal nicotine exposure [17,20,21].…”

Section: Introductionmentioning

confidence: 89%

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Developmental nicotine exposure induced alterations in behavior and glutamate receptor function in hippocampus

Parameshwaran

Buabeid

Karuppagounder

et al. 2011

Cell. Mol. Life Sci.

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In the developing brain, nicotinic acetylcholine receptors (nAChRs) are involved in cell survival, targeting, formation of neural and sensory circuits, and development and maturation of other neurotransmitter systems. This regulatory role is disrupted when the developing brain is exposed to nicotine, which occurs with tobacco use during pregnancy. Prenatal nicotine exposure has been shown to be a strong risk factor for memory deficits and other behavioral aberrations in the offspring. The molecular mechanisms underlying these neurobehavioral outcomes are not clearly elucidated. We used a rodent model to assess behavioral, neurophysiological, and neurochemical consequences of prenatal nicotine exposure in rat offspring with specific emphasis on the hippocampal glutamatergic system. Pregnant dams were infused with nicotine (6 mg/kg/day) subcutaneously from the third day of pregnancy until birth. Results indicate that prenatal nicotine exposure leads to increased anxiety and depressive-like effects and impaired spatial memory. Synaptic plasticity in the form of long-term potentiation (LTP), basal synaptic transmission, and AMPA receptor-mediated synaptic currents were reduced. The deficit in synaptic plasticity was paralleled by declines in protein levels of vesicular glutamate transporter 1 (VGLUT1), synaptophysin, AMPA receptor subunit GluR1, phospho(Ser845) GluR1, and postsynaptic density 95 (PSD-95). These results suggest that prenatal nicotine exposure by maternal smoking could result in alterations in the glutamatergic system in the hippocampus contributing to the abnormal neurobehavioral outcomes.

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Section: Introductionmentioning

confidence: 78%

Section: Introductionmentioning

confidence: 89%

Developmental nicotine exposure induced alterations in behavior and glutamate receptor function in hippocampus

Parameshwaran

Buabeid

Karuppagounder

et al. 2011

Cell. Mol. Life Sci.

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“…For example, studies in humans as well as laboratory animals indicate that perinatal exposure to nicotine impairs learning and memory later in life 41,42 and has lasting effects on the expression of nAChRs. 43 Likewise, altering the availability of choline during development affects learning when subjects are adults.…”

Section: Discussionmentioning

confidence: 99%

Exposure to Kynurenic Acid During Adolescence Produces Memory Deficits in Adulthood

Akagbosu

Evans

Gulick³

et al. 2010

Schizophrenia Bulletin

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The glia-derived molecule kynurenic acid (KYNA) is an antagonist of a7 nicotinic acetylcholine receptors and the glycine B binding site on n-methyl-d-aspartateglutamate receptors, both of which have critical roles in neural plasticity as well as learning and memory. KYNA levels are increased in the brains and cerebral spinal fluid of persons with schizophrenia, leading to the notion that changes in KYNA concentration might contribute to cognitive dysfunction associated with this disorder. Indeed, recent studies indicate that increasing endogenous KYNA concentration by administering l-kynurenine (L-KYN, the precursor of KYNA) impairs spatial as well as contextual learning and memory in adult rats. In the present study, rats were treated with L-KYN (100 mg/ kg) throughout adolescence to increase endogenous KYNA concentration during this critical time in brain development. Rats were then tested drug-free as adults to test the hypothesis that exposure to elevated levels of KYNA during development may contribute to cognitive dysfunction later in life. Consistent with prior studies in which adult rats were treated acutely with L-KYN, juvenile rats exposed to increased KYNA concentration during adolescence exhibited deficits in contextual fear memory, but cue-specific fear memory was not impaired. In addition, rats treated with L-KYN as adolescents were impaired on a novel object recognition memory task when tested as adults. The memory deficits could not be explained by drug-induced changes in locomotor activity or shock sensitivity. Together, these findings add to the growing literature supporting the notion that exposure to increased concentration of KYNA may contribute to cognitive deficits typically observed in schizophrenia.

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“…In line with the clinical data, deficits in learning and memory and sensory processing have also been detected. Rodents exposed in utero to nicotine performed poorly on tests of learning and memory, including the radial arm maze (Levin et al, 1993;Sorenson et al, 1991) and twoway active avoidance (Vaglenova et al, 2008). Similarly, mice exposed to nicotine via injection took longer to reach criterion on the radial arm maze and had increased latencies to reach the platform on the Morris water maze (Yanai et al, 1992).…”

Section: Tobacco/nicotinementioning

confidence: 99%

“…In fact, evidence exists that prenatal nicotine increases anxiety in rodents (Huang et al, 2007;Santiago and Huffman, 2013;Vaglenova et al, 2008), although also see Amos-Kroohs et al (2013). Exposed animals are more likely to self-administer nicotine later in life (Chistyakov et al, 2010;Levin et al, 2006).…”

Section: Tobacco/nicotinementioning

confidence: 99%

Developmental Consequences of Fetal Exposure to Drugs: What We Know and What We Still Must Learn

Ross

Graham

Money

et al. 2014

Neuropsychopharmacol

340

241

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Most drugs of abuse easily cross the placenta and can affect fetal brain development. In utero exposures to drugs thus can have long-lasting implications for brain structure and function. These effects on the developing nervous system, before homeostatic regulatory mechanisms are properly calibrated, often differ from their effects on mature systems. In this review, we describe current knowledge on how alcohol, nicotine, cocaine, amphetamine, Ecstasy, and opiates (among other drugs) produce alterations in neurodevelopmental trajectory. We focus both on animal models and available clinical and imaging data from cross-sectional and longitudinal human studies. Early studies of fetal exposures focused on classic teratological methods that are insufficient for revealing more subtle effects that are nevertheless very behaviorally relevant. Modern mechanistic approaches have informed us greatly as to how to potentially ameliorate the induced deficits in brain formation and function, but conclude that better delineation of sensitive periods, dose-response relationships, and long-term longitudinal studies assessing future risk of offspring to exhibit learning disabilities, mental health disorders, and limited neural adaptations are crucial to limit the societal impact of these exposures.

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Long-lasting teratogenic effects of nicotine on cognition: Gender specificity and role of AMPA receptor function

Cited by 62 publications

References 57 publications

Developmental nicotine exposure induced alterations in behavior and glutamate receptor function in hippocampus

Developmental nicotine exposure induced alterations in behavior and glutamate receptor function in hippocampus

Exposure to Kynurenic Acid During Adolescence Produces Memory Deficits in Adulthood

Developmental Consequences of Fetal Exposure to Drugs: What We Know and What We Still Must Learn

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