Calcium binding protein (calbindin-D28k) and glutamate decarboxylase gene expression after kindling induced seizures

Sonnenberg, June L.; Frantz, Gretchen; Lee, Soohee; Heick, Alison E.; Chu, Ching-Chi; Tobin, Allan J.; Christakos, Sylvia

doi:10.1016/0169-328x(91)90001-e

Cited by 69 publications

(12 citation statements)

References 30 publications

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“…It has been shown that calbindin gene expression is reduced in a genetic model of epilepsy (Montpied et al, 1995). Another study evaluating calbindin gene expression following acute seizures found that calbindin protein expression was decreased in the hippocampus; however, the mRNA levels were unchanged (Sonnenberg et al, 1991). To our knowledge, this is the first study that has demonstrated that in pilocarpine-induced AE, the observed decrease in hippocampal calbindin protein is associated with a significant down regulation calbindin gene expression.…”

Section: Discussionmentioning

confidence: 60%

Long-term decrease in calbindin-D28K expression in the hippocampus of epileptic rats following pilocarpine-induced status epilepticus

et al. 2008

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SummaryAcquired epilepsy (AE) is characterized by spontaneous recurrent seizures and long-term changes that occur in surviving neurons following an injury such as status epilepticus (SE). Long-lasting alterations in hippocampal Ca 2+ homeostasis have been observed in both in vivo and in vitro models of AE. One major regulator of Ca 2+ homeostasis is the neuronal calcium binding protein, calbindinD28k that serves to buffer and transport Ca 2+ ions. This study evaluated the expression of hippocampal calbindin levels in the rat pilocarpine model of AE. Calbindin protein expression was reduced over 50% in the hippocampus in epileptic animals. This decrease was observed in the pyramidal layer of CA1, stratum lucidum of CA3, hilus, and stratum granulosum and stratum moleculare of the dentate gyrus when corrected for cell loss. Furthermore, calbindin levels in individual neurons were also significantly reduced. In addition, the expression of calbindin mRNA was decreased in epileptic animals. Time course studies demonstrated that decreased calbindin expression was initially present 1 month following pilocarpine-induced SE and lasted for up to 2 years after the initial episode of SE. The results indicate that calbindin is essentially permanently decreased in the hippocampus in AE. This decrease in hippocampal calbindin may be a major contributing factor underlying some of the plasticity changes that occur in epileptogenesis and contribute to the alterations in Ca 2+ homeostasis associated with AE.

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Section: Discussionmentioning

confidence: 60%

Long-term decrease in calbindin-D28K expression in the hippocampus of epileptic rats following pilocarpine-induced status epilepticus

et al. 2008

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“…This might be the case also for En2 mutants, that display increased seizure susceptibility (Tripathi et al, 2009). Accordingly, the downregulation of CALB mRNA in the absence of a reduced number of CALB-positive neurons in the En2 −/− cortex might be related to hyperexcitability (Sonnenberg et al, 1991). …”

Section: Discussionmentioning

confidence: 99%

Loss of GABAergic neurons in the hippocampus and cerebral cortex of Engrailed-2 null mutant mice: Implications for autism spectrum disorders

Sgadò

Genovesi

Kalinovsky

et al. 2013

Experimental Neurology

102

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The homeobox-containing transcription factor Engrailed-2 (En2) is involved in patterning and neuronal differentiation of the midbrain/hindbrain region, where it is prominently expressed. En2 mRNA is also expressed in the adult mouse hippocampus and cerebral cortex, indicating that it might also function in these brain areas. Genome-wide association studies revealed that En2 is a candidate gene for autism spectrum disorders (ASD), and mice devoid of its expression (En2−/− mice) display anatomical, behavioural and clinical “autistic-like” features. Since reduced GABAergic inhibition has been proposed as a possible pathogenic mechanism of ASD, we hypothesized that the phenotype of En2−/− mice might include defective GABAergic innervation in the forebrain. Here we show that the Engrailed proteins are present in postnatal GABAergic neurons of the mouse hippocampus and cerebral cortex, and adult En2−/− mice show reduced expression of GABAergic marker mRNAs in these areas. In addition, reduction in parvalbumin (PV), somatostatin (SOM) and neuropeptide Y (NPY) expressing interneurons is detected in the hippocampus and cerebral cortex of adult En2−/− mice. Our results raise the possibility of a link between altered function of En2, anatomical deficits of GABAergic forebrain neurons and the pathogenesis of ASD.

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“…Cal 28k, a calcium binding protein involved in neuronal excitability [53], undergoes reduced expression in the basal forebrain and hippocampus both with normal aging and AD [54]. Our laboratory has previously shown significant reduction in Cal 28k expression in the hippocampus of Ts65Dn mice at 10 months of age, alleviated with anti-inflammatory or antioxidant treatment [13, 30].…”

Section: Discussionmentioning

confidence: 99%

A Noradrenergic Lesion Exacerbates Neurodegeneration in a Down Syndrome Mouse Model

Lockrow

Boger

Gerhardt

et al. 2011

JAD

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Individuals with Down syndrome (DS) acquire Alzheimer’s-like dementia (AD) and associated neuropathology earlier and at significantly greater rates than age-matched normosomic individuals. However, biological mechanisms have not been discovered and there is currently limited therapy for either DS- or AD-related dementia. Segmental trisomy 16 (Ts65Dn) mice provide a useful model for many of the degenerative changes which occur with age in DS including cognitive deficits, neuroinflammation, and degeneration of basal forebrain cholinergic neurons. Loss of noradrenergic locus coeruleus (LC) neurons is an early event in AD and in DS, and may contribute to the neuropathology. We report that Ts65Dn mice exhibit progressive loss of norepinephrine (NE) phenotype in LC neurons. In order to determine whether LC degeneration contributes to memory loss and neurodegeneration in Ts65Dn mice, we administered the noradrenergic neurotoxin N-(2-chloroethyl)-N-ethyl-2-bromobenzylamine (DSP-4; 2 doses of 50 mg/kg, i.p.) to Ts65Dn mice at four months of age, prior to working memory loss. At eight months of age, Ts65Dn mice treated with DSP-4 exhibited an 80% reduction in hippocampal NE, coupled with a marked increase in hippocampal neuroinflammation. Noradrenergic depletion also resulted in accelerated cholinergic neuron degeneration and a further impairment of memory function in Ts65Dn mice. In contrast, DSP-4 had minimal effects on normosomic littermates, suggesting a disease-modulated vulnerability to NE loss in the DS mouse model. These data suggest that noradrenergic degeneration may play a role in the progressive memory loss, neuroinflammation, and cholinergic loss occurring in DS individuals, providing a possible therapeutic avenue for future clinical studies.

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Calcium binding protein (calbindin-D28k) and glutamate decarboxylase gene expression after kindling induced seizures

Cited by 69 publications

References 30 publications

Long-term decrease in calbindin-D28K expression in the hippocampus of epileptic rats following pilocarpine-induced status epilepticus

Long-term decrease in calbindin-D28K expression in the hippocampus of epileptic rats following pilocarpine-induced status epilepticus

Loss of GABAergic neurons in the hippocampus and cerebral cortex of Engrailed-2 null mutant mice: Implications for autism spectrum disorders

A Noradrenergic Lesion Exacerbates Neurodegeneration in a Down Syndrome Mouse Model

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