Chronic prenatal ethanol exposure-induced decrease of guinea pig hippocampal CA1 pyramidal cell and cerebellar Purkinje cell density

2003 ◽  
Vol 81 (5) ◽  
pp. 476-484 ◽  
Author(s):  
Tara N McGoey ◽  
James N Reynolds ◽  
James F Brien
Keyword(s):  
Purkinje Cell ◽  
Purkinje Cells ◽  
Linear Density ◽  
Time Course ◽  
Pyramidal Cells ◽  
Ethanol Exposure ◽  
Prenatal Ethanol Exposure ◽  
Ca1 Pyramidal Cells ◽  
Hippocampal Ca1 ◽  
Cerebellar Purkinje Cells

The brain is a key target of ethanol teratogenicity, in which ethanol can produce neurodegeneration in selected areas, including the hippocampus and cerebellum. The research objective was to test the hypothesis that chronic prenatal ethanol exposure, via maternal ethanol administration, produces differential time course of decreased linear density of hippocampal CA1 pyramidal cells and cerebellar Purkinje cells. Timed pregnant guinea pigs received chronic oral administration of ethanol, isocaloric-sucrose/pair-feeding, or water throughout gestation (term, about gestational day (GD) 68), and the offspring were studied at GD 62 (near-term fetus), postnatal day (PD) 1 (neonate), PD 5, and PD 12 (early postnatal life). Ethanol treatment, compared with isocaloric-sucrose/pair-feeding and water treatments, decreased brain, hippocampal, and cerebellar weights at GD 62, PD 1, PD 5, and PD 12. Hippocampal CA1 pyramidal cell linear density and cerebellar Purkinje cell linear density were unaffected at GD 62. Ethanol treatment produced 25, 30, and 30% decreases in linear density of hippocampal CA1 pyramidal cells at PD 1, PD 5, and PD 12, respectively, and a 30% decrease in linear density of cerebellar Purkinje cells at PD 12 only. At PD 5, Purkinje cell profile linear density remained unaffected; however, ethanol treatment appeared to increase linear density of apoptotic Purkinje cell nuclei, as determined by a modified TUNEL method. The data demonstrate that chronic prenatal ethanol exposure produces apparent differential time course of decreased linear density of hippocampal CA1 pyramidal cells and cerebellar Purkinje cells in the developing guinea pig.Key words: prenatal ethanol exposure, hippocampal CA1 pyramidal cells, cerebellar Purkinje cells, decreased linear density, differential time course, guinea pig.

scholarly journals Acid-sensitive channel inhibition prevents fetal alcohol spectrum disorders cerebellar Purkinje cell loss

2008 ◽  
Vol 295 (2) ◽  
pp. R596-R603 ◽  
Author(s):  
Jayanth Ramadoss ◽  
Emilie R. Lunde ◽  
Nengtai Ouyang ◽  
Wei-Jung A. Chen ◽  
Timothy A. Cudd
Keyword(s):  
Purkinje Cell ◽  
Purkinje Cells ◽  
Granule Cells ◽  
Cell Number ◽  
Ethanol Exposure ◽  
Ph Sensitive ◽  
Mitigation Strategies ◽  
Cerebellar Purkinje Cell ◽  
Prenatal Ethanol Exposure ◽  
Channel Inhibition

Ethanol is now considered the most common human teratogen. Educational campaigns have not reduced the incidence of ethanol-mediated teratogenesis, leading to a growing interest in the development of therapeutic prevention or mitigation strategies. On the basis of the observation that maternal ethanol consumption reduces maternal and fetal pH, we hypothesized that a pH-sensitive pathway involving the TWIK-related acid-sensitive potassium channels (TASKs) is implicated in ethanol-induced injury to the fetal cerebellum, one of the most sensitive targets of prenatal ethanol exposure. Pregnant ewes were intravenously infused with ethanol (258 ± 10 mg/dl peak blood ethanol concentration) or saline in a “3 days/wk binge” pattern throughout the third trimester. Quantitative stereological analysis demonstrated that ethanol resulted in a 45% reduction in the total number of fetal cerebellar Purkinje cells, the cell type most sensitive to developmental ethanol exposure. Extracellular pH manipulation to create the same degree and pattern of pH fall caused by ethanol (manipulations large enough to inhibit TASK 1 channels), resulted in a 24% decrease in Purkinje cell number. We determined immunohistochemically that TASK 1 channels are expressed in Purkinje cells and that the TASK 3 isoform is expressed in granule cells of the ovine fetal cerebellum. Pharmacological blockade of both TASK 1 and TASK 3 channels simultaneous with ethanol effectively prevented any reduction in fetal cerebellar Purkinje cell number. These results demonstrate for the first time functional significance of fetal cerebellar two-pore domain pH-sensitive channels and establishes them as a potential therapeutic target for prevention of ethanol teratogenesis.

scholarly journals The effect of the timing of ethanol exposure during early postnatal life on total number of Purkinje cells in rat cerebellum

1999 ◽  
Vol 194 (3) ◽  
pp. 423-431
Author(s):  
TAKANORI MIKI ◽  
SIMON HARRIS ◽  
PETER WILCE ◽  
YOSHIKI TAKEUCHI ◽  
KULDIP S. BEDI
Keyword(s):  
Purkinje Cell ◽  
Purkinje Cells ◽  
Exposure Period ◽  
Ethanol Exposure ◽  
High Dose ◽  
Postnatal Life ◽  
Ethanol Vapour ◽  
Cell Numbers ◽  
Rat Cerebellum ◽  
Cerebellar Purkinje Cells

We have previously shown that exposing rats to a high dose of ethanol on postnatal d 5 can affect Purkinje cell numbers in the cerebellum whilst similar exposure on d 10 had no such effect. The question arose whether a longer period of ethanol exposure after d 10 could produce loss of Purkinje cells. We have examined this question by exposing young rats to a relatively high dose (∼420–430 mg/dl) of ethanol for 6 d periods between the ages of either 4 and 9 d or 10 and 15 d of age. Exposure was carried out by placing the rats in an ethanol vapour chamber for 3 h per day during the exposure period. Groups of ethanol-treated (ET), separation controls (SC) and mother-reared controls (MRC) were anaesthetised and killed when aged 30 d by perfusion with buffered 2.5% glutaraldehyde. Stereological methods were used to determine the numbers of Purkinje cells in the cerebellum of each rat. MRC, SC and rats treated with ethanol between 10–15 d of age each had, on average, about 254–258 thousand cerebellar Purkinje cells; the differences between these various groups were not statistically significant. However, the rats treated with ethanol vapour between 4–9 d of age had an average of only about 128000±20000 Purkinje cells per cerebellum. This value was significantly different from both the MRC and group-matched SC animals. It is concluded that the period between 4 and 9 d of age is an extremely vulnerable period during which the rat cerebellar Purkinje cells are particularly susceptible to the effects of a high dose of ethanol. However, a similar level and duration of ethanol exposure commencing after 10 d of age has no significant effect on Purkinje cell numbers.

scholarly journals Caffeine-Induced Suppression of GABAergic Inhibition and Calcium-Independent Metaplasticity

2016 ◽  
Vol 2016 ◽  
pp. 1-7 ◽  
Author(s):  
Masako Isokawa
Keyword(s):  
Time Course ◽  
Calcium Release ◽  
Critical Role ◽  
Pyramidal Cells ◽  
Ruthenium Red ◽  
Gabaergic Inhibition ◽  
Inward Current ◽  
Calcium Dependent ◽  
Ca1 Pyramidal Cells ◽  
Hippocampal Ca1

GABAergic inhibition plays a critical role in the regulation of neuron excitability; thus, it is subject to modulations by many factors. Recent evidence suggests the elevation of intracellular calcium ([Ca2+]i) and calcium-dependent signaling molecules underlie the modulations. Caffeine induces a release of calcium from intracellular stores. We tested whether caffeine modulated GABAergic transmission by increasing[Ca2+]i. A brief local puff-application of caffeine to hippocampal CA1 pyramidal cells transiently suppressed GABAergic inhibitory postsynaptic currents (IPSCs) by 73.2 ± 6.98%. Time course of suppression and the subsequent recovery of IPSCs resembled DSI (depolarization-induced suppression of inhibition), mediated by endogenous cannabinoids that require a[Ca2+]irise. However, unlike DSI, caffeine-induced suppression of IPSCs (CSI) persisted in the absence of a[Ca2+]irise. Intracellular applications of BAPTA and ryanodine (which blocks caffeine-induced calcium release from intracellular stores) failed to prevent the generation of CSI. Surprisingly, ruthenium red, an inhibitor of multiple calcium permeable/release channels including those of stores, induced metaplasticity by amplifying the magnitude of CSI independently of calcium. This metaplasticity was accompanied with the generation of a large inward current. Although ionic basis of this inward current is undetermined, the present result demonstrates that caffeine has a robustCa2+-independent inhibitory action on GABAergic inhibition and causes metaplasticity by opening plasma membrane channels.

scholarly journals The Entorhinal Cortical Alvear Pathway Differentially Excites Pyramidal Cells and Interneuron Subtypes in Hippocampal CA1

2020 ◽  
Author(s):  
Karen A Bell ◽  
Rayne Delong ◽  
Priyodarshan Goswamee ◽  
A Rory McQuiston
Keyword(s):  
Brain Slices ◽  
Pyramidal Cells ◽  
Excitatory Input ◽  
Theta Burst Stimulation ◽  
Ca1 Pyramidal Cells ◽  
Whole Cell Patch Clamp ◽  
Hippocampal Ca1 ◽  
Physiological Impact ◽  
Theta Burst ◽  
Synaptic Responses

Abstract The entorhinal cortex alvear pathway is a major excitatory input to hippocampal CA1, yet nothing is known about its physiological impact. We investigated the alvear pathway projection and innervation of neurons in CA1 using optogenetics and whole cell patch clamp methods in transgenic mouse brain slices. Using this approach, we show that the medial entorhinal cortical alvear inputs onto CA1 pyramidal cells (PCs) and interneurons with cell bodies located in stratum oriens were monosynaptic, had low release probability, and were mediated by glutamate receptors. Optogenetic theta burst stimulation was unable to elicit suprathreshold activation of CA1 PCs but was capable of activating CA1 interneurons. However, different subtypes of interneurons were not equally affected. Higher burst action potential frequencies were observed in parvalbumin-expressing interneurons relative to vasoactive-intestinal peptide-expressing or a subset of oriens lacunosum-moleculare (O-LM) interneurons. Furthermore, alvear excitatory synaptic responses were observed in greater than 70% of PV and VIP interneurons and less than 20% of O-LM cells. Finally, greater than 50% of theta burst-driven inhibitory postsynaptic current amplitudes in CA1 PCs were inhibited by optogenetic suppression of PV interneurons. Therefore, our data suggest that the alvear pathway primarily affects hippocampal CA1 function through feedforward inhibition of select interneuron subtypes.

Modeling Research on Spatiotemporal Dynamics of the Hippocampus

1997 ◽  
Vol 07 (01) ◽  
pp. 187-198 ◽  
Author(s):  
Haijian Sun ◽  
Lin Liu ◽  
Chunhua Feng ◽  
Aike Guo
Keyword(s):  
Pyramidal Cells ◽  
Behavioral Pattern ◽  
Spatiotemporal Dynamics ◽  
Epileptic Focus ◽  
Power Law Distribution ◽  
Ca1 Pyramidal Cells ◽  
Self Organized ◽  
Hippocampal Ca1 ◽  
Self Organized Criticality ◽  
Neurological Insult

The spatiotemporal dynamics of the hippocampus is studied. We first propose a fractal algorithm to model the growth of hippocampal CA1 pyramidal cells, together with an avalanche model for information transmission. Then the optical records of an epileptic focus in the hippocampus are analyzed and simulated. These processes indicate that the hippocampus normally stays in self-organized criticality with a harmonious spatiotemporal behavioral pattern, that is, showing 1/f fluctuation and power law distribution. In case of a neurological insult, the hippocampal system may step into supercriticality and initiate epilepsy.

Sign in / Sign up

Export Citation Format

Share Document