Background
Neuropeptide Y (NPY) has been implicated in depression, anxiety, and memory. Expression
of human NPY and the number of NPY-positive neurons in the rodent amygdala correlate
with anxiety and stress-related behavior. Increased NPY expression in the epileptic
brain is supposed to represent an adaptive mechanism counteracting epilepsy-related
hyperexcitability. We attempted to investigate whether NPY-positive neurons in the
human amygdala are involved in these processes.
Methods
In 34 adult epileptic patients undergoing temporal lobe surgery for seizure control,
the density of NPY-positive neurons was assessed in the basal, lateral, and accessory-basal
amygdala nuclei. Cell counts were related to self-reported depression, anxiety, quality
of life, clinical parameters (onset and duration of epilepsy, seizure frequency),
antiepileptic medication, and amygdala and hippocampal magnetic resonance imaging
volumetric measures.
Results
Densities of NPY-positive basolateral amygdala neurons showed significant positive
correlations with depression and anxiety scores, and they were negatively correlated
with lamotrigine dosage. In contrast, NPY cell counts showed no relation to clinical
factors or amygdalar and hippocampal volumes.
Conclusions
The results point to a role of amygdalar NPY in negative emotion and might reflect
state processes at least in patients with temporal lobe epilepsy. Correlations with
common clinical parameters of epilepsy were not found. The question of a disease-related
reduction of the density of NPY-positive amygdalar neurons in temporal lobe epilepsy
requires further investigation.
Key Words
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References
- Neuropeptide Y—A novel brain peptide with structural similarities to peptide YY and pancreatic polypeptide.Nature. 1982; 296: 659-660
- Central administration of neuropeptide Y induces hypotension bradypnea and EEG synchronization in the rat.Acta Physiol Scand. 1983; 118: 189-192
- Intracerebroventricular neuropeptide Y suppresses open field and home cage activity in the rat.Regul Pept. 1987; 19: 221-2311
- The NPY system in stress, anxiety and depression.Neuropeptides. 2004; 38: 213-224
- Recent developments in our understanding of the physiological role of PP-fold peptide receptor subtypes.Exp Biol Med. 2003; 228: 217-244
- Modulation of memory processing by neuropeptide Y varies with brain injection site.Brain Res. 1989; 503: 73-82
- Overexpression of NPY and Y2 receptors in epileptic brain tissue: An endogenous neuroprotective mechanism in temporal lobe epilepsy?.Neuropeptides. 2004; 38: 245-252
- Large-scale expression study of human mesial temporal lobe epilepsy: Evidence for dysregulation of the neurotransmission and complement systems in the entorhinal cortex.Brain. 2006; 29: 625-641
- Plasticity of Y1 and Y2 receptors and neuropeptide Y fibers in patients with temporal lobe epilepsy.J Neurosci. 2001; 21: 5804-5812
- Neuropeptide-Y immunoreactivity in the pilocarpine model of temporal lobe epilepsy.Exp Brain Res. 1997; 116: 186-190
- Seizure susceptibility of neuropeptide-Y null mutant mice in amygdala kindling and chemical-induced seizure models.Epilepsy Res. 2004; 61: 49-62
- Corticotropin-releasing factor and neuropeptide Y: Role in emotional integration.Trends Neurosci. 1994; 17: 80-85
- Interactions between NPY and CRF in the amygdala to regulate emotionality.Neuropeptides. 2004; 38: 225-234
- Contributions of the amygdala to emotion processing: from animal models to human behavior.Neuron. 2005; 48: 175-187
- Genetic variation in human NPY expression affects stress response and emotion.Nature. 2008; 452: 997-1001
- Amygdalar neuropeptide Y Y1 receptors mediate the anxiolytic-like actions of neuropeptide Y in the social interaction test.Eur J Pharmacol. 1999; 368: 143-147
- The role of neuropeptide Y in the amygdala on corticotropin-releasing factor receptor-mediated behavioral stress responses in the rat.Stress. 2006; 9: 21-28
- Contribution of amygdala neurons containing peptides and calcium-binding proteins to fear-potentiated startle and exploration-related anxiety in inbred Roman high- and low-avoidance rats.Eur J Neurosci. 2002; 15: 1206-1218
- Neonatal thyroxine treatment: Changes in the number of corticotropin-releasing-factor (CRF) and neuropeptide Y (NPY) immunoreactive neurons and density of tyrosine hydroxylase positive fibers (TH) in the amygdala correlate with anxiety-related behavior of Wistar rats.Neuroscience. 2004; 124: 283-297
- Affective aggression in patients with temporal lobe epilepsy: A quantitative MRI study of the amygdala.Brain. 2000; 123: 234-243
- Major depression in temporal lobe epilepsy with hippocampal sclerosis: Clinical and imaging correlates.J Neurol Neurosurg Psychiatry. 2007; 78: 1226-1230
- Depressed mood and memory impairment in temporal lobe epilepsy as a function of focus lateralization and localization.Epilepsy Behav. 2004; 5: 696-701
- Amygdaloid sclerosis in temporal lobe epilepsy.Ann Neurol. 1993; 33: 622-631
- Coexistence of GABA and peptide immunoreactivity in non-pyramidal neurons of the basolateral amygdala.Neurosci Lett. 1989; 100: 53-58
- Classification of projection neurons and interneurons in the rat lateral amygdala based upon cluster analysis.Mol Cell Neurosci. 2006; 33: 57-67
- Subregional pathology of the amygdala complex and entorhinal region in surgical specimens from patients with pharmacoresistant temporal lobe epilepsy.J Neuropathol Exp Neurol. 2000; 59: 907-920
- Neuronal loss and gliosis of the amygdaloid nucleus in temporal lobe epilepsy.Acta Neuropathol. 1997; 93: 606-610
- Amygdala damage in experimental and human temporal lobe epilepsy.Epilepsy Res. 1998; 32: 233-253
- Clinical relevance of amygdala sclerosis in temporal lobe epilepsy.J Neurosurg. 1999; 91: 59-67
- Axosomatic inhibition of projection neurons in the lateral nucleus of amygdala in human temporal lobe epilepsy: An ultrastructural study.Exp Brain Res. 2007; 177: 384-399
- Kognitive Therapie der Depressionen [cognitive therapy of depressions].Urban Schwarzenberg, Munich1981
- A rating instrument for anxiety disorders.Psychosomatics. 1971; 12: 371-379
- A brief questionnaire to screen for quality of life in epielpsy: The QOLIE-10.Epilepsia. 1996; 37: 577-582
- MRI in the presurgical evaluation of patients with drug-resistant epilepsies.AJNR Am J Neuroradiol. 2004; 25: 919-926
- Multivariate Statistical Methods.McGraw-Hill, New York1976
- Statistical Power Analysis for the Behavioral Sciences.2nd ed. Lawrence Erlbaum, Hillsdale, New Jersey1998
- Use of the Beck anxiety Inventory with adolescent psychiatric outpatients.Psychol Rep. 1995; 76: 459-465
- Common and specific dimensions of self-reported anxiety and depression: The BDI-II versus the BDI-IA.Behav Res Ther. 1998; 37: 183-190
- Depression and anxiety before and after temporal lobe epilepsy surgery.Seizure. 2004; 13: 129-135
- A retrospective analysis of hippocampal pathology in human temporal lobe epilepsy: Evidence for distinctive patient subcategories.Epilepsia. 2003; 44: 677-687
- Behavioral and endocrine adaptation, and upregulation of NPY expression in rat amygdala following repeated restraint stress.Neuroreport. 1999; 29: 3003-3007
- Altered neuropeptide Y and neurokinin messenger RNA expression and receptor binding in stress-sensitised rats.Brain Res. 2008; 1212: 35-47
- Search for biological correlates of depression and mechanisms of action of antidepressant treatment modalities.Physiol Behav. 2008; 9: 226-231
- CSF monoamine metabolites and neuropeptides in depressed patients before and after electroconvulsive therapy.Eur Psychiatry. 2008; 23: 356-359
- Reduced neuropeptide Y concentrations in suicide brain.J Neurochem. 1992; 59: 73-80
- Depressive symptoms in epilepsy: Prevalence, impact, aetiology, biological correlates and effect of treatment with antiepileptic drugs.Drugs. 2008; 68: 1493-1509
- Varicella zoster virus induces neuropathic changes in rat dorsal root ganglia and behavioral reflex sensitisation that is attenuated by gabapentin or sodium channel blocking drugs.Pain. 2005; 118: 97-111
- NADPH-diaphorase-positive cell populations in the human amygdala and temporal cortex: Neuroanatomy, peptidergic characteristics and aspects of aging and Alzheimer's disease.Acta Neuropathol. 1992; 83: 636-646
- Brain monoaminergic and neuropeptidergic variations in human aging.J Neural Transm. 1996; 103: 101-115
- Neuropeptide Y gene expression is increased in the hypothalamus of older women.J Clin Endocrinol Metab. 2004; 89: 2338-2343
- Brain-derived neurotrophic factor, phosphorylated cyclic AMP response element binding protein and neuropeptide Y decline as early as middle age in the dentate gyrus and CA1 and CA3 subfields of the hippocampus.Exp Neurol. 2005; 195: 353-371
- Retrograde tracing of nerve fibers to the rat middle cerebral artery with true blue: Colocalization with different peptides.J Cereb Blood Flow Metab. 1989; 9: 212-218
- Neuropeptide Y- and vasoactive intestinal polypeptide-containing nerve fibers in the human cerebral arteries: Characteristics of distribution.Angiology. 1991; 42: 35-43
- Development of cerebral arterial innervation: Synchronous development of neuropeptide Y (NPY)-and vasoactive intestinal polypeptide (VIP)-containing fibers and some observations on growth cones.Brain Res Dev Brain Res. 1992; 69: 77-83
- Catecholamine and NPY efferents from the ventrolateral medulla to the amygdala in the rat.Brain Res Bull. 1995; 38: 253-260
- Neuropeptide Y and epilepsy: Recent progress, prospects and controversies.Neuropeptides. 2004; 38: 261-265
- Levetiracetam prevents changes in levels of brain-derived neurotrophic factor and neuropeptide Y mRNA and of Y1- and Y5-like receptors in the hippocampus of rats undergoing amygdala kindling: Implications for antiepileptogenic and mood-stabilizing properties.Epilepsy Behav. 2004; 5: 204-215
- Neuropeptide Y and seizures: Effects of exogenously applied ligands.Neuropeptides. 2004; 38: 253-260
- Differential suppression of seizures via Y2 and Y5 neuropeptide Y receptors.Neurobiol Dis. 2005; 20: 760-772
- Differential actions of NPY on seizure modulation via Y1 and Y2 receptors: Evidence from receptor knockout mice.Epilepsia. 2006; 47: 773-780
- Neuropeptide Y (NPY) and depression: From animal studies to the human condition.Life Sci. 2002; 71: 2921-2937
- Physiology and gene regulation of the brain NPY Y1 receptor.Front Neuroendocrinol. 2006; 27: 308-339
- Neuropeptide Y (NPY) Y2 receptors mediate behaviour in two animal models of anxiety: Evidence from Y2 receptor knockout mice.Behav Brain Res. 2003; 15: 251-255
- Reduced anxiety and improved stress coping ability in mice lacking NPY-Y2 receptors.Eur J Neurosci. 2003; 18: 143-148
- Differential regulation of neuropeptide Y receptors in the brains of NPY knock-out mice.Peptides. 2001; 22: 395-403
- Recent advances in the neurobiology of anxiety disorders: Implications for novel therapeutics.Am J Med Genet C Semin Med Genet. 2008; 148: 89-98
- In the amygdala anxiolytic action of mGlu5 receptors antagonist MPEP involves neuropeptide Y but not GABAA signaling.Neuropsychopharmacology. 2004; 29: 514-521
- Anxiolytic action of Group II and III metabotropic glutamate receptors agonists involves neuropeptide Y in the amygdala.Pharmacol Rep. 2005; 57: 734-743
- Neuropeptide expression in rats exposed to chronic mild stresses.Psychopharmacology. 2005; 178: 115-124
- Neuropeptide systems as novel therapeutic targets for depression and anxiety disorders.Trends Pharmacol Sci. 2003; 24: 580-588
Article info
Publication history
Published online: June 01, 2009
Accepted:
March 29,
2009
Received in revised form:
March 10,
2009
Received:
July 10,
2008
Footnotes
Authors CF, JH, DY-H, and CH contributed equally to this work.
Identification
Copyright
© 2009 Society of Biological Psychiatry. Published by Elsevier Inc. All rights reserved.
