Parvalbumin immunoreactivity in the hippocampus of the gerbil after transient forebrain ischaemia: A qualitative and quantitative sequential study

doi:10.1016/0306-4522(93)90452-L

Neuroscience

Volume 55, Issue 1, July 1993, Pages 33-43

https://doi.org/10.1016/0306-4522(93)90452-L Get rights and content

Abstract

Parvalbumin immunoreactivity is examined in the hippocampus of the Mongolian gerbil (Meriones unguiculatus) in controls and in animals subjected to 20 min of forebrain ischaemia produced by bilateral clipping of the carotids. In comparison with other species, the hippocampus of the gerbil is characterized by strong immunoreactivity of the (presumably excitatory) perforant pathway, and weak immunoreactivity (low numbers of neurons and scarce dendritic arbors) in nonpyramidal nerve cells (inhibitory neurons) of the CA1 area. These properties may play some role in the development and maintenance of seizures in this susceptible species. Parvalbumin immunoreactivity is rapidly and ephemerally increased in the hippocampus 15 min after reperfusion. Later on, there is a transitory decrease of parvalbumin immunoreactivity which is followed by an increase 6 h later in the stratum granulare hilus and CA3 area, and not until the first and second days in the CA1 area. This increase significantly surpasses the number of immunoreactive neurons in control animals in CA1 and CA3 from 48 h after reperfusion onwards. The effect is similar using different anaesthetics and does not occur in sham-operated animals. In contrast with these findings, the number of parvalbumin-immunoreactive neurons in the somatosensory cortex is not affected in our model of forebrain ischaemia. On the other hand, GABA-immunoreactive neurons in CA1 are preserved during the first week after reperfusion, although an increase in the number of these cells occurs at the end of this period. Delayed neuronal death occurs in the CA1 area 48 h after ischaemia, and marked reduction in the number of CA1 neurons is found by the end of the first week. Eighty per cent of the remaining cells in CA1 at day 7, and 83% at day 15, are parvalbumin-immunoreactive nonpyramidal neurons in contrast to 3% parvalbumin-immunoreactive cells in control animals.

These findings indicate that GABAergic neurons in CA1 are preserved after forebrain ischaemia, and that parvalbumin in CA1 neurons is associated with survival.

References (70)

ArakiT. et al.
Neuronal damage and calcium accumulation following repeated brief cerebral ischemia in the gerbil
Brain Res.
(1990)
BaimbridgeK.G. et al.
Immunohistochemical localization of calcium-binding protein in the cerebellum, hippocampal formation and olfactory bulb of the rat
Brain Res.
(1982)
BustoR. et al.
Postischemic moderate hypothermia inhibits CA1 hippocampal ischemie neuronal injury
Neurosci. Lett.
(1989)
ChoiD.W.
Glutamate neurotoxicity and diseases of the nervous system
Neuron
(1988)
FreundT.F. et al.
Hippocampal cell death following ischemia, effects of brain temperature and anaesthesia
Expl Neurol.
(1990)
GotoK. et al.
Effects of cycloheximide on delayed neuronal death in rat hippocampus
Brain Res.
(1990)
HashimotoK. et al.
Changes in cerebral energy metabolism and calcium levels in relation to delayed neuronal death after ischemia
Neurosci. Lett.
(1992)
HeizmannC.W. et al.
Expression of parvalbumin and other Ca²⁺-binding proteins in normal and tumor cells: a topical review
Cell Calcium
(1987)
JohansenF.F. et al.
Short-term changes of parvalbumin and calbindin immunoreactivity in the rat hippocampus following cerebral ischemia
Neurosci. Lett.
(1990)
KawaguchiY. et al.
Fast spiking cells in the rat hippocampus (CA1 region) contain the calcium-binding protein parvalbumin
Brain Res.
(1987)

KirinoT.

Delayed neuronal death in the gerbil hippocmpus following transient ischemia

Brain Res.

(1982)

KosakaT. et al.

GABAergic neurons containing the Ca²⁺ binding protein parvalbumin in the rat hippocampus and dentate gyrus

Brain Res.

(1987)

MagnussonK. et al.

Impairment of protein ubiquitination may cause delayed neuronal death

Neurosci. Lett.

(1989)

MillerR.J.

The control of neuronal Ca²⁺ homeostasis

Prog. Neurobiol.

(1991)

NitschC. et al.

Preservation of GABAergic perikarya and boutons after transient ischemia in the gerbil hippocampal CA1 field

Brain Res.

(1989)

NitschC. et al.

GABAergic hippocampal neurons resistant to ischaemia induced delayed neuronal death contain the calcium-binding protein parvalbumin

Neurosci. Lett.

(1989)

NitschR. et al.

Late appearance of parvalbumin-immunore-activity in the development of GABAergic neurons in the rat hippocampus

Neurosci. Lett.

(1990)

PersechiniA. et al.

The EF-hand family of calcium modulated proteins

Trends Neurosci.

(1989)

SakamotoN. et al.

Disturbed Ca²⁺ homeostasis in the gerbil hippocampus following brief transient ischemia

Brain Res.

(1986)

SchlanderM. et al.

Glutamate decarboxylase-immunoreactive neurons in the aging rat hippocampus are more resistant to ischemia than CA1 pyramidal cells

Neurosci. Lett.

(1988)

Schmidt-KastnerR. et al.

Selective vulnerability of the hippocampus in brain ischemia

Neuroscience

(1991)

ShigenoT. et al.

Reduction of delayed neuronal death by inhibition of protein synthesis

Neurosci. Lett.

(1990)

SuzukiR. et al.

Microphysiology of selectively vulnerable neurons

Prog. Brain Res.

(1985)

TsudaT. et al.

Postischemic changes of calcium and endogenous anatagonist in the rat hippocampus studied by proton-induced X-ray emission analysis

Brain Res.

(1989)

WielochT.

Neurochemical correlates to selective neuronal vulnerability

YamamotoK. et al.

Cerebral ischemia in the gerbil: transmission electron microscopic and immunoelectron microscopic investigation

Brain Res.

(1986)

BergmannI. et al.

Area-specific morphological and neurochemical maturation of non-pyramidal neurons in the rat hippocampus as revealed by parvalbumin immunocytochemistry

Anat. Embryol.

(1991)

BonnekohP. et al.

Time profile of calcium accumulation in hippocampus, striatum and frontoparietal cortex after transient forebrain ischemia in the gerbil

Acta neuropath.

(1992)

BraakE. et al.

Parvalbumin-immunoreactivite structures in the hippocampus of the human adult

Cell Tiss. Res.

(1991)

BrierleyJ.B. et al.

Hypoxia and vascular disorders of the central nervous system

CelioM.R.

Calbindin D-28k and parvalbumin in the rat nervous system

Neuroscience

(1990)

CrainB.J. et al.

Selective neuronal death after transient forebrain ischemia in the Mongolian gerbil: a silver impregnation study

Neuroscience

(1988)

DeLeoJ. et al.

Ischemia-induced neuronal cell death, calcium accumulation, and glial response in the hippocampus of the Mongolian gerbil and protection by propentofylline (HWA 285)

J. cerebr. Blood Flow Metab.

(1987)

DeshpandeJ. et al.

Ultrastructural changes in the hippocampal CA1 region following transient cerebral ischemia: evidence against programmed cell death

Expl. Brain Res.

(1992)

DeshpandeJ.K. et al.

Calcium accumulation and neuronal damage in rat hippocampus following cerebral ischemia

J. cerebr. Blood Flow Metab.

(1987)

Cited by (88)

Antiepileptogenic and neuroprotective effect of mefloquine after experimental status epilepticus
2023, Epilepsy Research
Acquired temporal lobe epilepsy (TLE) characterized by spontaneous recurrent seizures (SRS) and hippocampal inhibitory neuron dysfunction is often refractory to current therapies. Gap junctional or electrical coupling between inhibitory neurons has been proposed to facilitate network synchrony and intercellular molecular exchange suggesting a role in both seizures and neurodegeneration. While gap junction blockers can limit acute seizures, whether blocking neuronal gap junctions can modify development of chronic epilepsy has not been examined. This study examined whether mefloquine, a selective blocker of Connexin 36 gap junctions which are well characterized in inhibitory neurons, can limit epileptogenesis and related cellular and behavioral pathology in a model of acquired TLE. A single, systemic dose of mefloquine administered early after pilocarpine-induced status epilepticus (SE) in rat reduced both development of SRS and behavioral co-morbidities. Immunostaining for interneuron subtypes identified that mefloquine treatment likely reduced delayed inhibitory neuronal loss after SE. Uniquely, parvalbumin expressing neurons in the hippocampal dentate gyrus appeared relatively resistant to early cell loss after SE. Functionally, whole cell patch clamp recordings revealed that mefloquine treatment preserved inhibitory synaptic drive to projection neurons one week and one month after SE. These results demonstrate that mefloquine, a drug already approved for malaria prophylaxis, is potentially antiepileptogenic and can protect against progressive interneuron loss and behavioral co-morbidities of epilepsy.
Estradiol ameliorates the reduction in parvalbumin expression induced by ischemic brain injury
2014, Neuroscience Letters
Estradiol plays a neuroprotective role against focal cerebral ischemia. Parvalbumin is an intracellular Ca²⁺-binding protein. It exerts a neuroprotective effect against cytotoxic Ca²⁺ overload. This study investigated whether estradiol modulates parvalbumin expression in focal cerebral ischemia and glutamate-induced neuronal cell death. Adult female rats were ovariectomied and treated with vehicle or estradiol prior to middle cerebral artery occlusion (MCAO). The cerebral cortex was collected 24 h after MCAO. A proteomics approach showed a decrease of parvalbumin in MCAO-operated animals, while estradiol prevented the MCAO-induced decrease in parvalbumin. Reverse transcription-PCR and Western blot analyses confirmed that estradiol treatment attenuated the MCAO-induced decrease in parvalbumin levels. The results of immunohistochemical staining showed that the number of parvalbumin-positive cells decreased in MCAO-operated animals, and estradiol prevented the MCAO-induced decrease in parvalbumin-positive cells. In cultured hippocampal cells, glutamate exposure raised the intracellular Ca²⁺ concentration, while estradiol treatment attenuated this increase. Moreover, estradiol prevented the decrease in parvalbumin induced by glutamate toxicity. These findings suggest that estradiol exerts a neuroprotective effect by preventing the MCAO-induced decrease of parvalbumin and by regulating intracellular Ca²⁺ levels.
Ferulic acid attenuates the focal cerebral ischemic injury-induced decrease in parvalbumin expression
2012, Neuroscience Letters
Ferulic acid exerts a neuroprotective effect through its anti-oxidant and anti-inflammation properties. Parvalbumin has calcium buffering capacity and protects neuronal cells from cytotoxic Ca²⁺ overload. This study investigated whether ferulic acid regulates parvalbumin expression in cerebral ischemia and glutamate toxicity-induced neuronal cell death. Male Sprague-Dawley rats were immediately treated with vehicle or ferulic acid (100 mg/kg, i.v.) after middle cerebral artery occlusion (MCAO), and cerebral cortex tissues were collected 24 h after MCAO. A proteomics approach elucidated the decrease of parvalbumin in MCAO-operated animals, and ferulic acid treatment attenuated the injury-induced decrease in parvalbumin expression. Moreover, RT-PCR and Western blot analyses clearly showed that ferulic acid treatment prevents the injury-induced decrease in parvalbumin levels. The number of parvalbumin-positive cells also decreased in MCAO-operated animals, and ferulic acid attenuated this injury-induced decrease in parvalbumin-positive cells. In cultured hippocampal cells, glutamate toxicity significantly increased the intracellular Ca²⁺ concentration, whereas this increase in Ca²⁺ levels was inhibited by ferulic acid treatment. In addition, ferulic acid treatment attenuated the glutamate exposure-induced decrease in parvalbumin levels. These results suggest that ferulic acid exerts a neuroprotective effect by attenuating the injury-induced decrease of parvalbumin and modulating intracellular Ca²⁺ levels.
Trimethyltin-induced hippocampal degeneration as a tool to investigate neurodegenerative processes
2011, Neurochemistry International
Citation Excerpt :
Interestingly, selective neuronal vulnerability has also been related to the expression of calcium-binding proteins in other human neurodegenerative diseases such as amyotrophic lateral sclerosis (ALS), in which motoneurons damaged late or infrequently express high levels of CB or PV (Alexianu et al., 1994; Ince et al., 1993), AD, in which interneurons expressing PV and CR are particularly resistant to neurodegeneration (Fonseca and Soriano, 1995; Hof et al., 1993) and Parkinson's disease, where a selective preservation of CR-containing dopaminergic neurons has been observed (Mouatt-Prigent et al., 1994). A protective role of PV in resistant cells has also been hypothesised in experimental models of degenerative brain diseases such as SOD1 transgenic mice (Ince et al., 1998; Beers et al., 2001), experimental ischaemia (Tortosa and Ferrer, 1993) and kainate-induced experimental epilepsy (Dudina, 2005). The molecular pathogenesis of TMT intoxication is believed to be a complex event, as TMT is able to affect multiple processes in sensitive cells.
Trimethyltin (TMT), an organotin compound with neurotoxicant effects selectively localised in the limbic system and especially marked in the hippocampus, is considered a useful tool to obtain an experimental model of neurodegeneration. Animals exposed to TMT develop behavioural alterations (hyperactivity and aggression), cognitive impairment (memory loss and learning impairment) and spontaneous seizures. TMT induces selective neuronal death involving the granular neurons of the Fascia Dentata and the pyramidal cells of the Cornu Ammonis, with a different pattern of severity and extension according to the various species studied and the dosage schedule. TMT-induced neurodegenerative events are associated with the activation of astrocytes and microglial cells and with the upregulation of proinflammatory cytokines. While the mechanisms by which TMT induces neurodegeneration are still not understood, many hypotheses seem to suggest that neuronal damage could be largely dependent on calcium overload. This review summarizes current data from in vivo and in vitro studies of the neurotoxic effects of TMT, focusing on the hypotheses regarding the mechanisms leading to neuronal death induced by the toxin.
Relationship between neuronal vulnerability and potassium-chloride cotransporter 2 immunoreactivity in hippocampus following transient forebrain ischemia
2008, Neuroscience
Citation Excerpt :
The precise mechanisms involved in delayed neuronal death following ischemia are complex and incompletely understood. Transient cerebral ischemia kills CA1 pyramidal cells of the hippocampus, whereas most CA1 interneurons survive (Johansen et al., 1987; Schlander et al., 1988; Nitsch et al., 1989; Freund et al., 1990a; Tortosa and Ferrer, 1993). However, some interneurons do exhibit degenerative changes and/or morphological abnormalities already at 12 h after ischemia (Freund and Magloczky, 1993) or weeks or months later (Fukuda et al., 1993; Arabadzisz and Freund, 1999).
Cation chloride cotransporters have been reported to be expressed in neurons in the hippocampus and to regulate intracellular Cl⁻ concentration. The neuron-specific K-Cl cotransporter 2 (KCC2) is necessary for maintaining the low intracellular chloride concentration required for the hyperpolarizing actions of GABA. In this study we examined the vulnerability of KCC2-containing neurons as well as the changes in the pattern of KCC2 distribution in the rat hippocampus following 15 min ischemia induced by four-vessel occlusion. Immunostaining for the 72 kDa heat shock protein (HSP-72) was used to investigate the extent of damage in neuronal populations previously shown to be vulnerable to ischemia. At 6–24 h after ischemia, when the pyramidal cells in the CA1 (subfield of cornu Ammonis) region showed no morphological signs of damage, a small rise of KCC2 immunoreactivity was already observed. After 2 days, when the CA1 pyramidal cells started to degenerate, a progressive downregulation of the KCC2 protein was visible. Interestingly, in the same areas, the parvalbumin containing interneurons showed no signs of ischemic damage, and KCC2 immunoreactivity was retained on their membrane surface. In CA1 pyramidal cells, the reduction in KCC2 expression may lead to an elevation of intracellular Cl⁻ concentration, which causes a shift in equilibrium potential toward more positive levels. Consequently, the reduction of the inhibitory action of GABA through downregulation of KCC2 function may be involved in the pathomechanisms of delayed neuronal death in the CA1 subfield.
Comparison of single- and repeated-ischemia-induced changes in expression of flip and flop splice variants of AMPA receptor subtypes GluR1 and GluR2 in the rats hippocampus CA1 subregion
2007, Journal of Pharmacological Sciences
In addition to their role in physiological activities, ionotropic glutamate α-amino-3-hydroxy-5-methyl-4-isoxazole propionate receptors (AMPARs) play an important role in neuronal death, especially that following ischemic insults. In this study, we examined the effect of single (SI) and twice repeated (RI)-4-vessel occlusion-ischemia on rat performance in the 8-armed radial maze test. Moreover, the effects of SI and RI on the AMPARs subunits glutamate receptor (GluR) 1 and GluR2 flip and flop variants composition in the CA1 subregion of the hippocampus were investigated using RT-PCR, normalized to glyceraldehyde-3-phosphate dehydrogenase (GAPDH), and expressed as their ratios to the latter. The results showed that SI and RI impaired the maze performance by decreasing correct choices and increasing the error choices, but RI increased error choices to a greater extent than the SI. The SI reduced only GluR1 flip/GAPDH on day 1. The SI did not alter ratios of GluR2 variants to those of GluR1. On the other hand, the RI decreased GluR2 flip and flop variants after 1 and 3 days, respectively, whereas after 7 days, it increased the flip variant of both GluR1 and GluR2. Moreover, the RI reduced ratios of GluR2 variants to those of GluR1. These results reveal the differential effects of the SI and RI on memory and expression of the AMPARs subunits GluR1 and GluR2 and their flip and flop variants in the CA1.

View all citing articles on Scopus

^*: Neurologist, Doctoral Fellow at the Unit of Neuropathology.

View full text

Parvalbumin immunoreactivity in the hippocampus of the gerbil after transient forebrain ischaemia: A qualitative and quantitative sequential study

Abstract

Brain Res.

Brain Res.

Neurosci. Lett.

Neuron

Expl Neurol.

Brain Res.

Neurosci. Lett.

Cell Calcium

Neurosci. Lett.

Brain Res.

Brain Res.

Brain Res.

Neurosci. Lett.

Prog. Neurobiol.

Brain Res.

Neurosci. Lett.

Neurosci. Lett.

Trends Neurosci.

Brain Res.

Neurosci. Lett.

Neuroscience

Neurosci. Lett.

Prog. Brain Res.

Brain Res.

Brain Res.

Area-specific morphological and neurochemical maturation of non-pyramidal neurons in the rat hippocampus as revealed by parvalbumin immunocytochemistry

Anat. Embryol.

Time profile of calcium accumulation in hippocampus, striatum and frontoparietal cortex after transient forebrain ischemia in the gerbil

Acta neuropath.

Parvalbumin-immunoreactivite structures in the hippocampus of the human adult

Cell Tiss. Res.

Hypoxia and vascular disorders of the central nervous system

Calbindin D-28k and parvalbumin in the rat nervous system

Neuroscience

Selective neuronal death after transient forebrain ischemia in the Mongolian gerbil: a silver impregnation study

Neuroscience

Ischemia-induced neuronal cell death, calcium accumulation, and glial response in the hippocampus of the Mongolian gerbil and protection by propentofylline (HWA 285)

J. cerebr. Blood Flow Metab.

Ultrastructural changes in the hippocampal CA1 region following transient cerebral ischemia: evidence against programmed cell death

Expl. Brain Res.

Calcium accumulation and neuronal damage in rat hippocampus following cerebral ischemia

J. cerebr. Blood Flow Metab.