Glutamate-stimulated neuropeptide Y mRNA expression in the rat dentate gyrus: A prominent role of metabotropic glutamate receptors

Schwarzer, Christoph; Sperk, Günther

doi:10.1002/(sici)1098-1063(1998)8:3<274::aid-hipo9>3.0.co;2-j

Cited by 26 publications

(14 citation statements)

References 62 publications

(71 reference statements)

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“…Accordingly, systemic KA injection in rats has shown that strong convulsions cause upregulation of NPY in granule cells while slight convulsions induce NPY upregulation in interneurons (Gruber et al, 1994). Furthermore, several studies demonstrated that high doses of glutamate agonists injected into one hippocampus provoke upregulation of NPY in contralateral interneurons (Gruber et al, 1994; Schwarzer and Sperk, 1998), whereas subneurodegenerative doses cause upregulation of NPY only ipsilaterally. Factors regulating NPY expression include interleukins (Barnea et al, 2001) or BDNF (Nawa et al, 1994) and, indeed, the increased expression of BDNF observed at 2 days after intrahippocampal KA injection in mice was stronger in the ipsilateral than in the contralateral granule cell layer (Heinrich et al, 2011).…”

Section: Discussionmentioning

confidence: 99%

Differential vulnerability of interneurons in the epileptic hippocampus

Marx¹,

Haas²,

Häussler³

2013

Front. Cell. Neurosci.

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The loss of hippocampal interneurons has been considered as one reason for the onset of temporal lobe epilepsy (TLE) by shifting the excitation-inhibition balance. Yet, there are many different interneuron types which show differential vulnerability in the context of an epileptogenic insult. We used the intrahippocampal kainate (KA) mouse model for TLE in which a focal, unilateral KA injection induces status epilepticus (SE) followed by development of granule cell dispersion (GCD) and hippocampal sclerosis surrounding the injection site but not in the intermediate and temporal hippocampus. In this study, we characterized the loss of interneurons with respect to septotemporal position and to differential vulnerability of interneuron populations. To this end, we performed intrahippocampal recordings of the initial SE, in situ hybridization for glutamic acid decarboxylase 67 (GAD67) mRNA and immunohistochemistry for parvalbumin (PV) and neuropeptide Y (NPY) in the early phase of epileptogenesis at 2 days and at 21 days after KA injection, when recurrent epileptic activity and GCD have fully developed. We show that SE extended along the entire septotemporal axis of both hippocampi, but was stronger at distant sites than at the injection site. There was an almost complete loss of interneurons surrounding the injection site and expanding to the intermediate hippocampus already at 2 days but increasing until 21 days after KA. Furthermore, we observed differential vulnerability of PV- and NPY-expressing cells: while the latter were lost at the injection site but preserved at intermediate sites, PV-expressing cells were gone even at sites more temporal than GCD. In addition, we found upregulation of GAD67 mRNA expression in dispersed granule cells and of NPY staining in ipsilateral granule cells and ipsi- and contralateral mossy fibers. Our data thus indicate differential survival capacity of interneurons in the epileptic hippocampus and compensatory plasticity mechanisms depending on the hippocampal position.

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Section: Discussionmentioning

confidence: 99%

Differential vulnerability of interneurons in the epileptic hippocampus

Marx¹,

Haas²,

Häussler³

2013

Front. Cell. Neurosci.

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“…S4). Consistent with this argument, it has been reported that ceramide can increase glutamate release via enhancing exocytosis (34) and glutamate can up-regulate NPY mRNA levels in CNS neurons (35). A number of the downstream metabolites of ceramide, such as sphingosine and sphigosine-1 phosphate, are implicated in signaling transduction pathways (29), so these metabolites might play roles in ceramide-mediated control of food intake and energy balance.…”

Section: Discussionmentioning

confidence: 99%

Important roles of brain-specific carnitine palmitoyltransferase and ceramide metabolism in leptin hypothalamic control of feeding

Gao

Zhu

Gao

et al. 2011

Proc. Natl. Acad. Sci. U.S.A.

100

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Brain-specific carnitine palmitoyltransferase-1 (CPT-1c) is implicated in CNS control of food intake. In this article, we explore the role of hypothalamic CPT-1c in leptin's anorexigenic actions. We first show that adenoviral overexpression of CPT-1c in hypothalamic arcuate nucleus of rats increases food intake and concomitantly up-regulates orexigenic neuropeptide Y (NPY) and Bsx (a transcription factor of NPY). Then, we demonstrate that this overexpression antagonizes the anorectic actions induced by central leptin or compound cerulenin (an inhibitor of fatty acid synthase). The overexpression of CPT-1c also blocks leptin-induced downregulations of NPY and Bsx. Furthermore, the anorectic actions of central leptin or cerulenin are impaired in mice with brain CPT-1c deleted. Both anorectic effects require elevated levels of hypothalamic arcuate nucleus (Arc) malonyl-CoA, a fatty acidmetabolism intermediate that has emerged as a mediator in hypothalamic control of food intake. Thus, these data suggest that CPT-1c is implicated in malonyl-CoA action in leptin's hypothalamic anorectic signaling pathways. Moreover, ceramide metabolism appears to play a role in leptin's central control of feeding. Leptin treatment decreases Arc ceramide levels, with the decrease being important in leptin-induced anorectic actions and downregulations of NPY and Bsx. Of interest, our data indicate that leptin impacts ceramide metabolism through malonyl-CoA and CPT-1c, and ceramide de novo biosynthesis acts downstream of both malonyl-CoA and CPT-1c in mediating their effects on feeding and expressions of NPY and Bsx. In summary, we provide insights into the important roles of malonyl-CoA, CPT-1c, and ceramide metabolism in leptin's hypothalamic signaling pathways. O besity is a major cause of insulin-resistance and diabetes. An imbalance between food intake and energy expenditure contributes to the development of obesity. The CNS regulates energy homeostasis with the hypothalamus playing a critical role (1, 2). Mounting evidence now shows that fatty acid metabolism in the hypothalamus plays important roles in the central regulation of energy homeostasis (3-17). In this regard, malonyl-CoA, an intermediate in fatty acid de novo biosynthesis, is emerging as a player in the hypothalamus (3,5,6,(8)(9)(10)(11)(12)(13).Hypothalamic malonyl-CoA metabolism has been implicated in leptin-induced anorectic actions (9, 12, 13). Leptin, an important physiological regulator of food intake and body weight, exerts its anorectic effects partly by inducing an increase in malonyl-CoA level in the hypothalamic arcuate nucleus (Arc) (12). In addition to fatty acid biosynthesis, recent data also suggest a role for carnitine palmitoyltransferase-1 (CPT-1), a key enzyme in mitochondrial fatty acid β-oxidation (7, 18), in hypothalamic regulation of energy balance. Fatty acid biosynthesis and β-oxidation are linked by malonyl-CoA-mediated inhibition of CPT-1 acyltransferase activity (12). In the hypothalamus, the CPT-1 liver isoform (CPT-1a) is the predominant t...

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“…Because activation of groups II and III mGluR increases NPY expression in the hippocampus (Smialowska and Bajkowska, 1997;Schwarzer and Sperk, 1998), this raises a possibility that the ␤-estradiol-induced increase in NPY expression may be induced indirectly by activation of the mGluR system. However, a single mGluR-activating stimulus within 24 h before the NPY assay already effectively increased the NPY expression (Smialowska and Bajkowska, 1997;Schwarzer and Sperk, 1998). Acute application of ␤-estradiol on hippocampal cultures has been shown to activate mGluRs (Boulware et al, 2005).…”

Section: Discussionmentioning

confidence: 99%

β-Estradiol Increases Dentate Gyrus Inhibition in Female Rats via Augmentation of Hilar Neuropeptide Y

Velı́šková

Velı́šek²

2007

J. Neurosci.

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The dentate gyrus filters incoming activity into the hippocampus proper. It plays a role in learning and memory and in pathological states such as epilepsy. Some of hilar interneurons of the dentate gyrus express neuropeptide Y (NPY), which modulates granule cell activity. A subpopulation of the NPY-expressing inhibitory interneurons is sensitive to seizure-induced damage. Pretreatment with ␤-estradiol in ovariectomized rats protects hilar interneurons against seizure-induced injury, including the NPY-containing damage-sensitive subpopulation. Here, we demonstrate that ␤-estradiol enhances NPY expression within the hilar interneurons. In vitro paired-pulse stimulation of the mixed perforant path revealed ␤-estradiol-induced augmentation of granule cell network inhibition, which at interstimulus intervals between 200 and 300 ms (corresponding to ϳ3-5 Hz) was NPY sensitive and involved Y 1 receptors, whereas it was insensitive to GABA B or metabotropic glutamate receptor antagonists. Additionally, ␤-estradiol pretreatment attenuated propagation of lowfrequency (3.3 or 5 Hz) burst activity through the dentate gyrus. Scavenging endogenous NPY by intracerebroventricular administration of anti-NPY antibody accelerated kainic acid-induced seizure onset and increased seizure-induced neuronal damage in the hilus compared with rats treated with ␤-estradiol alone. Together, we show that ␤-estradiol upregulates hilar NPY and that this leads to enhancement in dentate gyrus inhibition of incoming frequencies between 3 and 5 Hz. Such frequencies are similar to the discharge frequencies recorded during seizure initiation in some patients with epilepsy. Thus, ␤-estradiol-induced NPY-sensitive filtering of 3-5 Hz frequencies may be an important regulator of incoming seizure activity, but it could also serve a physiological purpose in modulating information flow into the hippocampus proper.

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Glutamate-stimulated neuropeptide Y mRNA expression in the rat dentate gyrus: A prominent role of metabotropic glutamate receptors

Cited by 26 publications

References 62 publications

Differential vulnerability of interneurons in the epileptic hippocampus

Differential vulnerability of interneurons in the epileptic hippocampus

Important roles of brain-specific carnitine palmitoyltransferase and ceramide metabolism in leptin hypothalamic control of feeding

β-Estradiol Increases Dentate Gyrus Inhibition in Female Rats via Augmentation of Hilar Neuropeptide Y

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