Hippocampal Long-Term Potentiation (LTP) is Reduced by a Coplanar PCB Congener

doi:10.1016/j.neuro.2004.03.014

NeuroToxicology

Volume 25, Issue 6, December 2004, Pages 981-988

https://doi.org/10.1016/j.neuro.2004.03.014 Get rights and content

Abstract

Neurotoxicity of polychlorinated biphenyls (PCBs) is usually ascribed to the ortho-substituted congeners. We have examined the effects of acute perfusion of 3,3′,4,4′-tetrachlorobiphenyl (PCB 77), a coplanar, dioxin-like congener, on long-term potentiation (LTP) in the Schaffer collateral-CA1 and the mossy fiber-CA3 pathways in mouse hippocampus. LTP in both pathways was blocked by PCB 77, with a threshold effect at a concentration of 1 μM. LTP is a useful model of learning and memory function in which a patterned stimulation of an afferent pathway produces a persistent increase in the efficacy of synaptic transmission. LTP is reduced by PCB mixtures and ortho-substituted congeners at concentrations comparable to those studied here. These observations provide evidence in support of the hypothesis that dioxin-like and non-dioxin-like PCB congeners are equally potent in causing the cognitive decrements seen in children exposed prenatally to PCBs.

Section snippets

INTRODUCTION

Polychlorinated biphenyls (PCBs) are commercial mixtures which contain a large number of different chemical compounds, varying in the numbers of and positions of the chlorine molecules around the biphenyl ring. PCBs have a number of different health effects in that they are carcinogenic, immunosuppresive, neurotoxic, alter hepatic function and disrupt various endocrine systems (ATSDR, 2000, Carpenter, 1998).

PCBs are often considered to be of two primary groups: those like 2,3,7,8-tetrachloro-p

MATERIALS AND METHODS

ICR mice were used for all experiments (Taconic Farms Inc., Germantown, NY).

Animals were euthanized by cervical dislocation, the brains quickly removed and placed in ice-cold Krebs–Ringer solution (about 0–1 °C) which was oxygenated with 95% O₂–5% CO₂ and in which NaCl was replaced with iso-osmotic sucrose (Aghajanian and Rasmussen, 1989). Slices (about 400 μm in thickness) were cut using a vibrating razor blade slicer. They were made nearly perpendicular to the long axis of the hippocampus.

RESULTS

Fig. 1 shows raw data (upper traces) and pooled data (A) of LTP in the Schaffer collateral pathway to CA1 and (B) in the mossy fiber pathway to CA3 in the absence and in the presence of perfusion with PCB 77 added to the Krebs–Ringer. In the raw data records, the control response, after the brief stimulus artifact and a small presynaptic volley, is the extracellularly recorded population fEPSP, which reflects the monosynaptic activation of the many pyramidal neurons by the axons of the Schaffer

DISCUSSION

These results indicate that a coplanar PCB congener is effective in blocking LTP in a mouse hippocampus after acute administration at a concentration similar to that which blocked LTP by the di-ortho PCB 153 previously studied in rat slices (Carpenter et al., 2002, Hussain et al., 2000). This is an important conclusion for several reasons. There is a general perception that coplanar PCBs act only via activation of the Ah receptor. This is unlikely to be the case here, since the decremental

References (45)

G.K. Aghajanian et al.
Intracellular studies in the facial nucleus illustrating a simple new method for obtaining viable motoneurons in adult rat brain slices
Synapse
(1989)
L. Altmann et al.
Maternal exposure to polychlorinated biphenyls inhibits long-term potentiation in the visual cortex of adult rats
Neurosci Lett
(1995)
ATSDR (Agency for Toxic Substances and Disease Registry). Toxicological Profile for Polychlorinated Biphenyls....
D.H. Barrett et al.
Serum dioxin and cognitive functioning among veterans of Operation Ranch Hand
Neurotoxicology
(2001)
A. Bernhoft et al.
Effects of pre- and postnatal exposure to 3,3′4,4′,5-pentachlorobiphenyl on physical development, neurobehavior and xenobiotic metabolizing enzymes in rats
Environ Toxicol Chem
(1994)
Bushnell PJ, Rice DC. Behavioral assessments of learning and attention in rats exposed perinatally to...
D.O. Carpenter
Polychlorinated biphenyls and human health
Int J Occup Med Environ Health
(1998)
D.O. Carpenter et al.
Electrophysiologic and behavioral effects of perinatal and acute exposure of rats to lead and polychlorinated biphenyls
Environ Health Perspect
(2002)
D.O. Carpenter et al.
Flow cytometric measurements of neuronal death triggered by PCBs
Neurotoxicology
(1997)
Y.C. Chen et al.
Cognitive development of Yu-Cheng (“oil disease”) children prenatally exposed to heat-degraded PCBs
JAMA
(1992)

P. Eriksson et al.

Developmental neurotoxicity of four ortho-substituted polychlorinated biphenyls in the neonatal mouse

Environ Toxicol Pharmacol

(1996)

P. Eriksson et al.

Neurotoxic effects in adult mice neonatally exposed to 3,3′4,4′,5-pentachlorobiphenyl or 2,3,3′,4, 4′-pentachlorobiphenyl. Changes in brain nicotinic receptors and behavior

Environ Toxicol Pharmacol

(1998)

P. Eriksson et al.

Neonatal exposure to 3,3′,4, 4′-tetrachlorobiphenyl: changes in spontaneous behavior and cholinergic muscarinic receptors in the adult mouse

Toxicology

(1991)

O. Faroon et al.

Effects of polychlorinated biphenyls on the nervous system

Toxicol Ind Health

(2000)

L.J. Fischer et al.

Symposium overview: toxicity of non-coplanar PCBs

Toxicol Sci

(1998)

M.E. Gilbert et al.

Developmental exposure to a commercial PCB mixture (Aroclor 1254) produces a persistent impairment in long-term potentiation in the rat dentate gyrus in vivo

Brain Res

(1999)

Hansen L. The ortho side of PCBs: occurrence and disposition. Boston, MA: Kluwer Academic Publisher;...

J. Hany et al.

Behavioral effects following single and combined maternal exposure to PCB 77 (3,4,3′,4′-tetrachlorobiphenyl) and PCB 47 (2,4,2′,4′-tetrachlorobiphenyl) in rats

Neurotoxicol Teratol

(1999)

R.J. Hussain et al.

The effects of protein kinase C activity on synaptic transmission in two areas of rat hippocampus

Brain Res

(2003)

R.J. Hussain et al.

In vivo and in vitro exposure to PCB 153 reduces long-term potentiation

Environ Health Perspect

(2000)

J.L. Jacobson et al.

Intellectual impairment in children exposed to polychlorinated biphenyls in utero

N Engl J Med

(1996)

P.R.S. Kodavanti et al.

Comparative effects of two polychlorinated biphenyl congeners on calcium homeostasis in rat cerebellar granule cells

Toxicol Appl Pharmacol

(1993)

Cited by (33)

Effects of chronic high fat diet on mediobasal hypothalamic satiety neuron function in POMC-Cre mice
2024, Molecular Metabolism
The prevalence of obesity has increased over the past three decades. Proopiomelanocortin (POMC) neurons in the hypothalamic arcuate nucleus (ARC) play a vital role in induction of satiety. Chronic consumption of high-fat diet is known to reduce hypothalamic neuronal sensitivity to hormones like leptin, thus contributing to the development and persistence of obesity. The functional and morphological effects of a high-calorie diet on POMC neurons and how these effects contribute to the development and maintenance of the obese phenotype are not fully understood. For this purpose, POMC-Cre transgenic mice model was exposed to high-fat diet (HFD) and at the end of a 3- and 6-month period, electrophysiological and morphological changes, and the role of POMC neurons in homeostatic nutrition and their response to leptin were thoroughly investigated.
Effects of HFD on POMC-satiety neurons in transgenic mice models exposed to chronic high-fat diet were investigated using electrophysiological (patch-clamp), chemogenetic and Cre recombinase advanced technological methods. Leptin, glucose and lipid profiles were determined and analyzed.
In mice exposed to a high-fat diet for 6 months, no significant changes in POMC dendritic spine number or projection density from POMC neurons to the paraventricular hypothalamus (PVN), lateral hypothalamus (LH), and bed nucleus stria terminalis (BNST) were observed. It was revealed that leptin hormone did not change the electrophysiological activities of POMC neurons in mice fed with HFD for 6 months. In addition, chemogenetic stimulation of POMC neurons increased HFD consumption. In the 3-month HFD-fed group, POMC activation induced an orexigenic response in mice, whereas switching to a standard diet was found to abolish orexigenic behavior in POMC mice.
Chronic high fat consumption disrupts the regulation of POMC neuron activation by leptin. Altered POMC neuron activation abolished the neuron's characteristic behavioral anorexigenic response. Change in nutritional content contributes to the reorganization of developing maladaptations.
Protective effects of chronic humanin treatment in mice with diabetic encephalopathy: A focus on oxidative stress, inflammation, and apoptosis
2023, Behavioural Brain Research
Diabetes is known to cause cognitive impairments through various mechanisms, including oxidative stress, inflammation, and apoptosis. Humanin (HN) has been shown to have protective effects on cognitive impairments induced by factors such as Aβ, muscarinic receptor antagonists, and aging in rodents. However, the mechanisms underlying the protective effects of HN in the prefrontal cortex and hippocampus in the context of diabetes are not well understood. In this study, we aimed to investigate the potential protective role of HN on oxidative stress, inflammation, and apoptosis in mice with diabetes.
We divided the mice into four groups, including a control group (treated with saline), a humanin group (treated with 4 mg/kg of HN), a streptozotocin (STZ) group (diabetic control), and an STZ+Humanin group. The mice were administered HN daily for 15 days. Our results showed that in the prefrontal cortex and hippocampus of the diabetes group, oxidative stress parameters, pro-inflammatory cytokines, apoptosis and, blood glucose levels were increased, while antioxidant and anti-inflammatory cytokines were diminished compared to the control group. However, HN treatment was able to modulate these markers, including blood glucose and the markers of oxidative stress, inflammation, and apoptosis.
In conclusion, our findings suggest that hyperglycemia, oxidative stress, inflammation, and apoptosis may contribute to the development of diabetes-induced cognitive impairments. By regulating these changes with HN treatment, we may be able to positively contribute to the treatment of cognitive impairments induced by diabetes.
Effects of endocrine disruptors on the electrical activity of leptin receptor neurons in the dorsomedial hypothalamus and anxiety-like behavior in male mice
2023, Environmental Pollution
There is increasing concern about the effects of endocrine disrupting chemicals (EDCs) on human health. Recently, some EDCs are suggested to affect energy metabolism leading to increased risk of obesity. Obesogenic effects of some EDCs on adipogenesis have been reported, however, there is no study examining their potential actions on the brain circuits controlling feeding and metabolism. We have investigated effects of tributyltin (TBT) and dichlorodiphenyltrichloroethane (p,p'-DDT) on electrical activity on dorsomedial hypothalamic leptin receptor neurons (DMH^LepR), morphological adaptations in neuronal anatomy of DMH^LepR, locomotion, and anxiety-like behaviors in mice. Twenty-three Lep-Cre transgenic mice were intracranially injected with GFP virus. Control animals received intraperitoneal corn oil alone while group 2 and 3 received TBT (25 μg/kg) and p,p'-DDT (2 mg/kg) for one month. Locomotor activity and anxiety-like behavior of the animals were determined by open field test. Electrophysiological effects of TBT and p,p'-DDT on DMH^LepR neurons were determined by patch clamp method. Neuronal anatomy was determined by confocal microscopy. Spontaneous firing frequency of DMH^LepR neurons of TBT group of mice was significantly higher than both p,p'-DDT and control groups (p < 0.01). TBT and p,p'-DDT significantly decreased frequency of the spontaneous inhibitory post-synaptic currents to DMH^LepR neurons compared to the control group (p < 0.05). The time spent in the center and the number of entrances to the center by the TBT-administered mice were significantly lower than other groups (p < 0.01). The total distance traveled and mean speed of the control group of mice were significantly higher than the p,p'-DDT- and TBT-administered animals (p < 0.0001). c-Fos activity of the p,p'-DDT- and TBT-administered animals were significantly elevated compared to the control group (p < 0.001), while no change in the number of dendritic spines were observed. In conclusion, this study demonstrates that exposure to TBT and p,p'-DDT alters electrical activity in DMH^LepR neurons and behavioral state in mice.
Investigation of obesogenic effects of hexachlorobenzene, DDT and DDE in male rats
2022, General and Comparative Endocrinology
Obesity has become a very important public health problem and is increasing globally. Genetics, individual and environmental factors play roles in the etiology of this complex disorder. Recently, several environmental pollutants have been suggested to have obesogenic activities. Peroxisome proliferator activating receptor gamma (PPARγ), uncoupling protein-1 (UCP1) and their expression in white adipose tissue (WAT) and brown adipose tissue (BAT) play key roles in adipogenesis. UCP3 and irisin were reported to play roles in non-shivering thermogenesis. Our primary aim was to investigate obesogenic effects of hexachlorobenzene (HCB), dichlorodiphenyltrichloroethane (DDT) and dichlorodiphenyldichloroethylene (DDE) in rats. In addition, thermoregulatory effects of HCB, DDT and DDE were also investigated by analyzing the levels of Ucp3 and irisin. Thirty-two adult male Sprague-Dawley rats were randomly divided into four groups as control, HCB, DDT and DDE. Animals were administered with organochlorine pesticides (OCPs; 5 mg/kg bw) by oral gavage every other day for five weeks. At the end of the experimental period, the animals were sacrificed, BAT and WAT samples were collected to analyze Pparγ, Ucp1 and Ucp3 levels. Moreover, skeletal muscle samples were collected to examine Ucp3 and irisin levels. Serum glucose, cholesterol and triglyceride levels were also determined. Body weight and core temperature of the animals were not significantly affected by any of the OCP administration. Serum glucose, cholesterol and triglyceride levels were similar among the experimental groups. Pparγ expression was significantly elevated by HCB administration only in WAT (p < 0.05). On the other hand, both Pparγ and Ucp1 expressions were diminished in WAT and BAT (p < 0.01) by DDT treatment, while in WAT, DDE significantly decreased Pparγ expression without altering its expression in BAT (p < 0.001). Ucp3 and irisin levels in skeletal muscle were not altered. Our findings show that both DDT and DDE reduce the browning of WAT by suppressing white adipocytes and thus may have obesogenic activity in male rats without altering thermoregulation. In addition, HCB, DDT and DDE-induced alterations in expression of Pparγ and Ucp1 in WAT implicates differential regulation of adipogenic processes.
Endocrine disruptors also function as nervous disruptors and can be renamed endocrine and nervous disruptors (ENDs)
2021, Toxicology Reports
Endocrine disruption (ED) and endocrine disruptors (EDs) emerged as scientific concepts in 1995, after numerous chemical pollutants were found to be responsible for reproductive dysfunction. The World Health Organization established in the United Nations Environment Programme a list of materials, plasticizers, pesticides, and various pollutants synthesized from petrochemistry that impact not only reproduction, but also hormonal functions, directly or indirectly. Cells communicate via either chemical or electrical signals transmitted within the endocrine or nervous systems. To investigate whether hormone disruptors may also interfere directly or indirectly with the development or functioning of the nervous system through either a neuroendocrine or a more general mechanism, we examined the scientific literature to ascertain the effects of EDs on the nervous system, specifically in the categories of neurotoxicity, cognition, and behaviour. To date, we demonstrated that all of the 177 EDs identified internationally by WHO are known to have an impact on the nervous system. Furthermore, the precise mechanisms underlying this neurodisruption have also been established. It was previously believed that EDs primarily function via the thyroid. However, this study presents substantial evidence that approximately 80 % of EDs operate via other mechanisms. It thus outlines a novel concept: EDs are also neurodisruptors (NDs) and can be collectively termed endocrine and nervous disruptors (ENDs). Most of ENDs are derived from petroleum residues, and their various mechanisms of action are similar to those of “spam” in electronic communications technologies. Therefore, ENDs can be considered as an instance of spam in a biological context.
Developmental perfluorooctane sulfonate exposure inhibits long-term potentiation by affecting AMPA receptor trafficking
2019, Toxicology
Citation Excerpt :
The hippocampus was quickly dissected and frozen in liquid nitrogen, and was stored at −80 °C. On PND 90, input/output (I/O) curves, paired-pulse facilitation (PPF) and long-term potentiation (LTP) were detected as previously described (Ozcan et al., 2004; Xing et al., 2009; Zhang et al., 2016a) with minor modifications (detailed in Supplementary Information). Briefly, six rats at PND90 from each group were anesthetized with urethane (1.5 g/kg bw).
Both animal study and epidemiological survey revealed the associations between defects of cognitive function and the developmental exposure to perfluorooctane sulfonate (PFOS), while the mechanism is not well known. The SD rats were exposed PFOS at 1.7, 5 and 15 mg/L by drinking water from gestation to the adulthood of the pups for evaluating the effects of PFOS exposure on long-term potentiation (LTP) and the role of α-amino-3-hydroxy-5-methyl-4-isoxazole propionic acid (AMPA) receptors trafficking. Whole-life exposure of PFOS beginning in utero to adulthood significantly inhibited the induction and expression of LTP, and the input/output curve (I/O) and paired-pulse facilitation (PPF) were moderately suppressed, suggesting that PFOS might affect the synaptic transmission and plasticity both in pre- and post-synaptic cells. Meanwhile, PFOS decreased the mRNA levels of AMPA receptor subunits GluA1 and GluA2, and the protein amounts in the membrane, with the total GluA1 and GluA2 protein amounts increased, indicating the internalization of AMPA receptors. Furthermore, tests in the primary hippocampal neurons also support the decreased mRNA levels of GluA1 and GluA2 induced by PFOS. After the pretreatment of AMPA antagonist (NBQX), PFOS decreased the expression of GluA1 and GluA2 and increased internal cellular calcium at much lower levels than that in the neurons without NBQX treatment. The results provide electrophysiological evidence for the impaired cognitive function induced by PFOS exposure and revealed the critical role of AMPA receptor involved.

View all citing articles on Scopus

^†: Present address: Faculty of Medicine, Firat University, Elazig, Turkey.

View full text

Hippocampal Long-Term Potentiation (LTP) is Reduced by a Coplanar PCB Congener

Abstract

Section snippets

INTRODUCTION

MATERIALS AND METHODS

RESULTS

DISCUSSION

Intracellular studies in the facial nucleus illustrating a simple new method for obtaining viable motoneurons in adult rat brain slices

Synapse

Maternal exposure to polychlorinated biphenyls inhibits long-term potentiation in the visual cortex of adult rats

Neurosci Lett

Serum dioxin and cognitive functioning among veterans of Operation Ranch Hand

Neurotoxicology

Effects of pre- and postnatal exposure to 3,3′4,4′,5-pentachlorobiphenyl on physical development, neurobehavior and xenobiotic metabolizing enzymes in rats

Environ Toxicol Chem

Polychlorinated biphenyls and human health

Int J Occup Med Environ Health

Electrophysiologic and behavioral effects of perinatal and acute exposure of rats to lead and polychlorinated biphenyls

Environ Health Perspect

Flow cytometric measurements of neuronal death triggered by PCBs

Neurotoxicology

Cognitive development of Yu-Cheng (“oil disease”) children prenatally exposed to heat-degraded PCBs

JAMA

Developmental neurotoxicity of four ortho-substituted polychlorinated biphenyls in the neonatal mouse

Environ Toxicol Pharmacol

Neurotoxic effects in adult mice neonatally exposed to 3,3′4,4′,5-pentachlorobiphenyl or 2,3,3′,4, 4′-pentachlorobiphenyl. Changes in brain nicotinic receptors and behavior

Environ Toxicol Pharmacol

Neonatal exposure to 3,3′,4, 4′-tetrachlorobiphenyl: changes in spontaneous behavior and cholinergic muscarinic receptors in the adult mouse

Toxicology

Effects of polychlorinated biphenyls on the nervous system

Toxicol Ind Health

Symposium overview: toxicity of non-coplanar PCBs

Toxicol Sci

Developmental exposure to a commercial PCB mixture (Aroclor 1254) produces a persistent impairment in long-term potentiation in the rat dentate gyrus in vivo

Brain Res

Behavioral effects following single and combined maternal exposure to PCB 77 (3,4,3′,4′-tetrachlorobiphenyl) and PCB 47 (2,4,2′,4′-tetrachlorobiphenyl) in rats

Neurotoxicol Teratol

The effects of protein kinase C activity on synaptic transmission in two areas of rat hippocampus

Brain Res

In vivo and in vitro exposure to PCB 153 reduces long-term potentiation

Environ Health Perspect

Intellectual impairment in children exposed to polychlorinated biphenyls in utero

N Engl J Med

Comparative effects of two polychlorinated biphenyl congeners on calcium homeostasis in rat cerebellar granule cells

Toxicol Appl Pharmacol