Article
Decreased glutamate release correlates with elevated dynorphin content in the hippocampus of aged rats with spatial learning deficits
Abstract
The effects of aging on extracellular glutamate and tissue dynorphin content in the hippocampus were examined in Fischer‐344 rats. Young adult (4‐month‐old) and aged (24‐month‐old) rats were trained to find a hidden platform in the Morris water task. Aged rats were unable to acquire the spatial learning task as rapidly as young controls. Following behavioral testing, an in vivo microdialysis perfusion method was used to determine extracellular glutamate levels in the hippocampus. There was a 25–35% reduction in extracellular glutamate concentration in both dorsal and ventral hippocampus of aged rats compared to young rats, in the absence of any change in tissue glutamate levels. Radioimmunoassay showed an increase in dynorphin A(1–8)‐like immunoreactivity [DYN‐A(1–8)LI] in both dorsal and ventral hippocampus, but not striatum, of aged rats. Immunocytochemistry indicated that this increase was localized to the dentate granule cells and mossy fibers. Furthermore, among the aged rats the increase in DYN‐A(1–8)LI was inversely correlated with the decrease in extracellular glutamate. These results suggest that the disregulation of dynorphin observed in cognitively impaired aged rats is related to reduced excitatory transmission within the hippocampal formation.
Citing Literature
Number of times cited according to CrossRef: 43
- Moriah L. Jacobson, Hildegard A. Wulf, Caroline A. Browne and Irwin Lucki, Opioid modulation of cognitive impairment in depression, The Opioid System as the Interface between the Brain’s Cognitive and Motivational Systems, 10.1016/bs.pbr.2018.07.007, (1-48), (2018).
- Kristen R. Hollinger, Jesse Alt, Alison M. Riehm, Barbara S. Slusher and Adam I. Kaplin, Dose-dependent inhibition of GCPII to prevent and treat cognitive impairment in the EAE model of multiple sclerosis, Brain Research, 1635, (105), (2016).
- Karita Raudkivi, Aet Alttoa, Ivo Leito and Jaanus Harro, Differences in extracellular glutamate levels in striatum of rats with high and low exploratory activity, Pharmacological Reports, 67, 5, (858), (2015).
- A. Bilkei-Gorzo, D. Mauer, K. Michel and A. Zimmer, Dynorphins regulate the strength of social memory, Neuropharmacology, 77, (406), (2014).
- Monika Mishra, Rameshwar Singh, Somnath Mukherjee and Deepak Sharma, Dehydroepiandrosterone's antiepileptic action in FeCl3-induced epileptogenesis involves upregulation of glutamate transporters, Epilepsy Research, 106, 1-2, (83), (2013).
- Katsuya Harada, Kazuhiro Nakato, Junko Yarimizu, Mayako Yamazaki, Masahiko Morita, Shinji Takahashi, Masaki Aota, Kyoko Saita, Hitoshi Doihara, Yuichiro Sato, Takayuki Yamaji, Keni Ni and Nobuya Matsuoka, A novel glycine transporter-1 (GlyT1) inhibitor, ASP2535 (4-[3-isopropyl-5-(6-phenyl-3-pyridyl)-4H-1,2,4-triazol-4-yl]-2,1,3-benzoxadiazole), improves cognition in animal models of cognitive impairment in schizophrenia and Alzheimer's disease, European Journal of Pharmacology, 685, 1-3, (59), (2012).
- Caroline Ménard, Rémi Quirion and Mark P. Mattson, Successful Cognitive Aging in Rats: A Role for mGluR5 Glutamate Receptors, Homer 1 Proteins and Downstream Signaling Pathways, PLoS ONE, 7, 1, (e28666), (2012).
- Kurt Hauser, Pamela Knapp, Tatiana Yakovleva, Dineke Verbeek and Georgy Bakalkin, Dynorphins in Central Nervous System Pathology, Neuropeptides in Neuroprotection and Neuroregeneration, 10.1201/b12279-7, (2012).
- Michelle L. Stephens, Jorge E. Quintero, Francois Pomerleau, Peter Huettl and Greg A. Gerhardt, Age-related changes in glutamate release in the CA3 and dentate gyrus of the rat hippocampus, Neurobiology of Aging, 10.1016/j.neurobiolaging.2009.05.009, 32, 5, (811-820), (2011).
- Xuan V. Nguyen, Mei Liu, Hyoung-Chun Kim and Guoying Bing, Effects of prodynorphin deletion on striatal dopamine in mice during normal aging and in response to MPTP, Experimental Neurology, 219, 1, (228), (2009).
- R. Minkeviciene, J. Ihalainen, T. Malm, O. Matilainen, V. Keksa‐Goldsteine, G. Goldsteins, H. Iivonen, N. Leguit, J. Glennon, J. Koistinaho, P. Banerjee and H. Tanila, Age‐related decrease in stimulated glutamate release and vesicular glutamate transporters in APP/PS1 transgenic and wild‐type mice, Journal of Neurochemistry, 105, 3, (584-594), (2007).
- Gong Cheng Zuo, Jing Yu Yang, Yue Hao, Ying Xu Dong and Chun Fu Wu, Ethanol and acetaldehyde induce similar changes in extracellular levels of glutamate, taurine and GABA in rat anterior cingulate cortex, Toxicology Letters, 169, 3, (253), (2007).
- Shengming Yin, Zhuo Guan, Yiyuan Tang, Jie Zhao, Jaushyong Hong and Wanqin Zhang, Abnormal expression of epilepsy-related gene ERG1/NSF in the spontaneous recurrent seizure rats with spatial learning memory deficits induced by kainic acid, Brain Research, 1053, 1-2, (195), (2005).
- Kenichi Tokita, Tatsuo Inoue, Shunji Yamazaki, Feng Wang, Takayuki Yamaji, Nobuya Matsuoka and Seitaro Mutoh, FK962, a novel enhancer of somatostatin release, exerts cognitive-enhancing actions in rats, European Journal of Pharmacology, 527, 1-3, (111), (2005).
- Carrie T. Drake and Charles Chavkin, Dendritic Dynorphin Release in the Hippocampal Formation, Dendritic Neurotransmitter Release, 10.1007/0-387-23696-1_17, (257-268), (2005).
- Catherine M. Kotz, Derik Weldon, Charles J. Billington and Allen S. Levine, Age-related changes in brain proDynorphin gene expression in the rat, Neurobiology of Aging, 25, 10, (1343), (2004).
- Juan Nacher, Gregori Alonso-Llosa, Daniel R Rosell and Bruce S McEwen, NMDA receptor antagonist treatment increases the production of new neurons in the aged rat hippocampus, Neurobiology of Aging, 24, 2, (273), (2003).
- W.D.J Van de Berg, A Blokland, A.C Cuello, C Schmitz, W Vreuls, H.W.M Steinbusch and C.E Blanco, Perinatal asphyxia results in changes in presynaptic bouton number in striatum and cerebral cortex—a stereological and behavioral analysis, Journal of Chemical Neuroanatomy, 20, 1, (71), (2000).
- Hansjörg Sauer, Jonathan M Francis, Hong Jiang, Gregory S Hamilton and Joseph P Steiner, Systemic treatment with GPI 1046 improves spatial memory and reverses cholinergic neuron atrophy in the medial septal nucleus of aged mice, Brain Research, 842, 1, (109), (1999).
- Peter R. Rapp, Edward C. Stack and Michela Gallagher, Morphometric studies of the aged hippocampus: I. Volumetric analysis in behaviorally characterized rats, Journal of Comparative Neurology, 403, 4, (459-470), (1998).
- Bruce S. McEwen, Stress and the Aging Hippocampus, Frontiers in Neuroendocrinology, 20, 1, (49), (1999).
- T. J. Baird, S. A. Vanecek, R. J. Briscoe, M. Vallett, K. L. Carl and D. V. Gauvin, Moderate, Long‐Term, Alcohol Consumption Potentiates Normal, Age‐Related Spatial Memory Deficits in Rats, Alcoholism: Clinical and Experimental Research, 22, 3, (628-636), (2006).
- J Sandin, I Nylander, J Georgieva, P.A Schött, S.O Ögren and L Terenius, Hippocampal dynorphin B injections impair spatial learning in rats: a κ-opioid receptor-mediated effect, Neuroscience, 85, 2, (375), (1998).
- Tsutomu Araki, Hiroyuki Kato, Sumiko Nagaki, Katsuro Shuto, Takehiko Fujiwara and Yasuto Itoyama, Effects of vinconate on age-related alterations in [3H]MK-801, [3H]glycine, sodium-dependent d-[3H]aspartate, [3H]FK-506 and [3H]PN200-110 binding in rats, Mechanisms of Ageing and Development, 95, 1-2, (13), (1997).
- Kathryn J. Jeffery, LTP and spatial learning—Where to next?, Hippocampus, 7, 1, (95-110), (1998).
- Jin-Hui Wang, Gladys Y. P. Ko and Paul T. Kelly, Cellular and Molecular Bases of Memory: Synaptic and Neuronal Plasticity, Journal of Clinical Neurophysiology, 14, 4, (264), (1997).
- Tsutomu Araki, Hiroyuki Kato, Katsuro Shuto, Takehiko Fujiwara and Yasuto Itoyama, Different age-related changes in NMDA and glycine receptors in the rat brain, Environmental Toxicology and Pharmacology, 1, 2, (103), (1996).
- L. Thai, J.S. Hong, R.G. Wiley and M. Gallagher, The regulation of hippocampal dynorphin by neural/neuroendocrine pathways: models for effects of aging on an opioid peptide system, Neuroscience, 70, 3, (661), (1996).
- Alan H. Nagahara, T.Michael Gill, Michelle Nicolle and Michela Gallagher, Alterations in opiate receptor binding in the hippocampus of aged Long-Evans rats, Brain Research, 707, 1, (22), (1996).
- Kimberly B. Bjugstad, Vladimir M. Mahnir, William R. Kem, Debra J. Socci and Gary W. Arendash, Long‐term treatment with GTS‐21 or nicotine enhances water maze performance in aged rats without affecting the density of nicotinic receptor subtypes in neocortex, Drug Development Research, 39, 1, (19-28), (1998).
- M.M Nicolle, J.L Bizon and M Gallagher, In vitro autoradiography of ionotropic glutamate receptors in hippocampus and striatum of aged Long–Evans rats: relationship to spatial learning, Neuroscience, 74, 3, (741), (1996).
- Michele L Simmons, Gregory W Terman, Sarah M Gibbs and Charles Chavkin, L-type calcium channels mediate dynorphin neuropeptide release from dendrites but not axons of hippocampal granule cells, Neuron, 14, 6, (1265), (1995).
- Yoshifumi Watanabe, Nancy G. Weiland and Bruce S. McEwen, Effects of adrenal steroid manipulations and repeated restraint stress on dynorphin mRNA levels and excitatory amino acid receptor binding in hippocampus, Brain Research, 680, 1-2, (217), (1995).
- Stanley Barone, Mark E. Stanton and William R. Mundy, Neurotoxic effects of neonatal triethyltin (TET) exposure are exacerbated with aging, Neurobiology of Aging, 16, 5, (723), (1995).
- Y. Yanovsky, J. Brankacˇk and H.L. Haas, Differences of CA3 bursting in DBA/1 and DBA/2 inbred mouse strains with divergent shuttle ☐ performance, Neuroscience, 64, 2, (319), (1995).
- D.E. Fordyce and J.M. Whner, Effects of aging on spatial learning and hippocampal protein kinase c in mice, Neurobiology of Aging, 14, 4, (309), (1993).
- Robert K. McNamara and Ronald W. Skelton, The neuropharmacological and neurochemical basis of place learning in the Morris water maze, Brain Research Reviews, 18, 1, (33), (1993).
- Michela Gallagher and Michelle M. Nicolle, Animal models of normal aging: Relationship between cognitive decline and markers in hippocampal circuitry, Behavioural Brain Research, 57, 2, (155), (1993).
- Alan H. Nagahara, Michelle M. Nicolle and Michela Gallagher, Alterations in [3H]‐kainate receptor binding in the hippocampal formation of aged long‐evans rats, Hippocampus, 3, 3, (269-277), (2004).
- Gayle A. Olson, Richard D. Olson and Abba J. Kastin, Endogenous opiates: 1991, Peptides, 13, 6, (1247), (1992).
- C. A. Barnes, G. Rao, T. C. Foster and B. L. McNaughton, Region‐specific age effects on AMPA sensitivity: Electrophysiological evidence for loss of synaptic contacts in hippocampal field CA1, Hippocampus, 2, 4, (457-468), (2004).
- Peter R. Rapp and David G. Amaral, Individual differences in the cognitive and neurobiological consequences of normal aging, Trends in Neurosciences, 15, 9, (340), (1992).
- Linda Thai, Paul H.K. Lee, Jack Ho, Harold Suh and John S. Hong, Regulation of prodynorphin gene expression in the hippocampus by glucocorticoids, Molecular Brain Research, 16, 1-2, (150), (1992).
