Blockade of dopamine D3 receptors improves hippocampal synaptic function and rescues age-related cognitive phenotype.
aging
dopamine D3 receptors
hippocampus
memory
synaptic plasticity
Journal
Aging cell
ISSN: 1474-9726
Titre abrégé: Aging Cell
Pays: England
ID NLM: 101130839
Informations de publication
Date de publication:
05 Sep 2024
05 Sep 2024
Historique:
revised:
22
06
2024
received:
01
03
2024
accepted:
16
07
2024
medline:
5
9
2024
pubmed:
5
9
2024
entrez:
5
9
2024
Statut:
aheadofprint
Résumé
Dopamine D3 receptors (D3Rs) modulate neuronal activity in several brain regions including the hippocampus. Although previous studies reported that blocking D3Rs exerts pro-cognitive effects, their involvement in hippocampal synaptic function and memory in the healthy and aged brain has not been thoroughly investigated. We demonstrated that in adult wild type (WT) mice, D3R pharmacological blockade or genetic deletion as in D3 knock out (KO) mice, converted the weak form of long-term potentiation (LTP1) into the stronger long-lasting LTP (LTP2) via the cAMP/PKA pathway, and allowed the formation of long-term memory. D3R effects were mainly mediated by post-synaptic mechanisms as their blockade enhanced basal synaptic transmission (BST), AMPAR-mediated currents, mEPSC amplitude, and the expression of the post-synaptic proteins PSD-95, phospho(p)GluA1 and p-CREB. Consistently, electron microscopy revealed a prevalent expression of D3Rs in post-synaptic dendrites. Interestingly, with age, D3Rs decreased in axon terminals while maintaining their levels in post-synaptic dendrites. Indeed, in aged WT mice, blocking D3Rs reversed the impairment of LTP, BST, memory, post-synaptic protein expression, and PSD length. Notably, aged D3-KO mice did not exhibit synaptic and memory deficits. In conclusion, we demonstrated the fundamental role of D3Rs in hippocampal synaptic function and memory, and their potential as a therapeutic target to counteract the age-related hippocampal cognitive decline.
Types de publication
Journal Article
Langues
eng
Sous-ensembles de citation
IM
Pagination
e14291Subventions
Organisme : Italian Ministry of University and Research
ID : PRIN 2020AMLXHH
Organisme : Italian Ministry of University and Research
ID : PRIN 2022BZWEK
Organisme : Italian Ministry of University and Research
ID : PRIN 2022YEPFB7
Organisme : University of Catania Progetto Piaceri
Organisme : Italian Ministry of Health Ricerca Corrente Fondazione IRCCS Policlinico Univ Ricerca Corrente IRCCS Oasi Research Institute
Informations de copyright
© 2024 The Author(s). Aging Cell published by Anatomical Society and John Wiley & Sons Ltd.
Références
Accili, D., Fishburn, C. S., Drago, J., Steiner, H., Lachowicz, J. E., Park, B. H., Gauda, E. B., Lee, E. J., Cool, M. H., Sibley, D. R., Gerfen, C. R., Westphal, H., & Fuchs, S. (1996). A targeted mutation of the D3 dopamine receptor gene is associated with hyperactivity in mice. Proceedings of the National Academy of Sciences of the United States of America, 93, 1945–1949.
Aceto, G., Nardella, L., Nanni, S., Pecci, V., Bertozzi, A., Colussi, C., D'Ascenzo, M., & Grassi, C. (2022). Activation of histamine type 2 receptors enhances intrinsic excitability of medium spiny neurons in the nucleus accumbens. Journal of Physiology, 600, 2225–2243. https://doi.org/10.1113/JP282962
Acquarone, E., Argyrousi, E. K., van den Berg, M., Gulisano, W., Fà, M., Staniszewski, A., Calcagno, E., Zuccarello, E., D'Adamio, L., Deng, S. X., Puzzo, D., Arancio, O., & Fiorito, J. (2019). Synaptic and memory dysfunction induced by tau oligomers is rescued by up‐regulation of the nitric oxide cascade. Molecular Neurodegeneration, 14, 26. https://doi.org/10.1186/s13024‐019‐0326‐4
Berry, A. S., Shah, V. D., Baker, S. L., Vogel, J. W., O'Neil, J. P., Janabi, M., Schwimmer, H. D., Marks, S. M., & Jagust, W. J. (2016). Aging affects dopaminergic neural mechanisms of cognitive flexibility. The Journal of Neuroscience, 36, 12559–12569. https://doi.org/10.1523/JNEUROSCI.0626‐16.2016
Blokland, A., & Sesia, T. (2023). Delay‐dependent forgetting in object recognition and object location test is dependent on strain and test. Behavioural Brain Research, 437, 114161. https://doi.org/10.1016/j.bbr.2022.114161
Bollen, E., Puzzo, D., Rutten, K., Privitera, L., De Vry, J., Vanmierlo, T., Kenis, G., Palmeri, A., D'Hooge, R., Balschun, D., Steinbusch, H. M., Blokland, A., & Prickaerts, J. (2014). Improved long‐term memory via enhancing cGMP‐PKG signaling requires cAMP‐PKA signaling. Neuropsychopharmacology, 39(11), 2497–2505. https://doi.org/10.1038/npp.2014.106
Castro‐Hernández, J., Afonso‐Oramas, D., Cruz‐Muros, I., Salas‐Hernández, J., Barroso‐Chinea, P., Moratalla, R., Millan, M. J., & González‐Hernández, T. (2015). Prolonged treatment with pramipexole promotes physical interaction of striatal dopamine D3 autoreceptors with dopamine transporters to reduce dopamine uptake. Neurobiology of Disease, 74, 325–335. https://doi.org/10.1016/j.nbd.2014.12.007
D'Amico, A. G., Scuderi, S., Leggio, G. M., Castorina, A., Drago, F., & D'Agata, V. (2013). Increased hippocampal CREB phosphorylation in dopamine D3 receptor knockout mice following passive avoidance conditioning. Neurochemical Research, 38, 2516–2523. https://doi.org/10.1007/s11064‐013‐1164‐3
Ehrlich, I., & Malinow, R. (2004). Postsynaptic density 95 controls AMPA receptor incorporation during long‐term potentiation and experience‐driven synaptic plasticity. The Journal of Neuroscience, 24, 916–927. https://doi.org/10.1523/JNEUROSCI.4733‐03.2004
Gross, G., Wicke, K., & Drescher, K. U. (2013). Dopamine D₃ receptor antagonism—still a therapeutic option for the treatment of schizophrenia. Naunyn Schmiedebergs Archive of Pharmacology, 386, 155–166. https://doi.org/10.1007/s00210‐012‐0806‐3
Gulisano, W., Melone, M., Ripoli, C., Tropea, M. R., Li Puma, D. D., Giunta, S., Cocco, S., Marcotulli, D., Origlia, N., Palmeri, A., Arancio, O., Conti, F., Grassi, C., & Puzzo, D. (2019). Neuromodulatory action of picomolar extracellular Aβ42 oligomers on presynaptic and postsynaptic mechanisms underlying synaptic function and memory. The Journal of Neuroscience, 39, 5986–6000. https://doi.org/10.1523/JNEUROSCI.0163‐19.2019
Gulisano, W., Tropea, M. R., Arancio, O., Palmeri, A., & Puzzo, D. (2018). Sub‐efficacious doses of phosphodiesterase 4 and 5 inhibitors improve memory in a mouse model of Alzheimer's disease. Neuropharmacology, 138, 151–159. https://doi.org/10.1016/j.neuropharm.2018.06.002
Hemby, S. E., Trojanowski, J. Q., & Ginsberg, S. D. (2003). Neuron‐specific age‐related decreases in dopamine receptor subtype mRNAs. The Journal of Comparative Neurology, 456, 176–183. https://doi.org/10.1002/cne.10525
Huang, M., Kwon, S., Oyamada, Y., Rajagopal, L., Miyauchi, M., & Meltzer, H. Y. (2015). Dopamine D3 receptor antagonism contributes to blonanserin‐induced cortical dopamine and acetylcholine efflux and cognitive improvement. Pharmacological Biochemical Behavior, 138, 49–57. https://doi.org/10.1016/j.pbb.2015.09.011
Kaasinen, V., Vilkman, H., Hietala, J., Någren, K., Helenius, H., Olsson, H., Farde, L., & Rinne, J. (2000). Age‐related dopamine D2/D3 receptor loss in extrastriatal regions of the human brain. Neurobiology of Aging, 21, 683–688. https://doi.org/10.1016/s0197‐4580(00)00149‐4
Kessels, H. W., & Malinow, R. (2009). Synaptic AMPA receptor plasticity and behavior. Neuron, 61, 340–350. https://doi.org/10.1016/j.neuron.2009.01.015
Kiss, B., Laszlovszky, I., Krámos, B., Visegrády, A., Bobok, A., Lévay, G., Lendvai, B., & Román, V. (2021). Neuronal dopamine D3 receptors: Translational implications for preclinical research and CNS disorders. Biomolecules, 11, 104. https://doi.org/10.3390/biom11010104
Klinker, F., Köhnemann, K., Paulus, W., & Liebetanz, D. (2017). Dopamine D3 receptor status modulates sexual dimorphism in voluntary wheel running behavior in mice. Behavioural Brain Research, 333, 235–241. https://doi.org/10.1016/j.bbr.2017.06.043
Laszy, J., Laszlovszky, I., & Gyertyán, I. (2005). Dopamine D3 receptor antagonists improve the learning performance in memory‐impaired rats. Psychopharmacology, 179, 567–575. https://doi.org/10.1007/s00213‐004‐2096‐z
Leggio, G. M., Di Marco, R., Gulisano, W., D'Ascenzo, M., Torrisi, S. A., Geraci, F., Lavanco, G., Dahl, K., Giurdanella, G., Castorina, A., Aitta‐Aho, T., Aceto, G., Bucolo, C., Puzzo, D., Grassi, C., Korpi, E. R., Drago, F., & Salomone, S. (2019). Dopaminergic‐GABAergic interplay and alcohol binge drinking. Pharmacological Research, 141, 384–391. https://doi.org/10.1016/j.phrs.2019.01.022
Leggio, G. M., Torrisi, S. A., Mastrogiacomo, R., Mauro, D., Chisari, M., Devroye, C., Scheggia, D., Nigro, M., Geraci, F., Pintori, N., Giurdanella, G., Costa, L., Bucolo, C., Ferretti, V., Sortino, M. A., Ciranna, L., De Luca, M. A., Mereu, M., Managò, F., … Papaleo, F. (2021). The epistatic interaction between the dopamine D3 receptor and dysbindin‐1 modulates higher‐order cognitive functions in mice and humans. Molecular Psychiatry, 26, 1272–1285. https://doi.org/10.1038/s41380‐019‐0511‐4
Li, Y., & Kuzhikandathil, E. V. (2012). Molecular characterization of individual D3 dopamine receptor‐expressing cells isolated from multiple brain regions of a novel mouse model. Brain Structure & Function, 217, 809–833. https://doi.org/10.1007/s00429‐012‐0383‐8
Liu, P., Xing, B., Chu, Z., Liu, F., Lei, G., Zhu, L., Gao, Y., Chen, T., & Dang, Y. H. (2017). Dopamine D3 receptor knockout mice exhibit abnormal nociception in a sex‐different manner. Journal of Neuroscience Research, 95, 1438–1445. https://doi.org/10.1002/jnr.23952
Liu, X. Y., Mao, L. M., Zhang, G. C., Papasian, C. J., Fibuch, E. E., Lan, H. X., Zhou, H. F., Xu, M., & Wang, J. Q. (2009). Activity‐dependent modulation of limbic dopamine D3 receptors by CaMKII. Neuron, 61, 425–438. https://doi.org/10.1016/j.neuron.2008.12.015
Maramai, S., Gemma, S., Brogi, S., Campiani, G., Butini, S., Stark, H., & Brindisi, M. (2016). Dopamine D3 receptor antagonists as potential therapeutics for the treatment of neurological diseases. Frontiers in Neuroscience, 10, 451. https://doi.org/10.3389/fnins.2016.00451
Meador‐Woodruff, J. H., Grandy, D. K., Van Tol, H. H., Damask, S. P., Little, K. Y., Civelli, O., & Watson, S. J., Jr. (1994). Dopamine receptor gene expression in the human medial temporal lobe. Neuropsychopharmacology, 10, 239–248. https://doi.org/10.1038/npp.1994.27
Melone, M., Ciriachi, C., Pietrobon, D., & Conti, F. (2019). Heterogeneity of astrocytic and neuronal GLT‐1 at cortical excitatory synapses, as revealed by its colocalization with Na+/K+‐ATPase α isoforms. Cerebral Cortex, 29, 3331–3350. https://doi.org/10.1093/cercor/bhy203
Micale, V., Cristino, L., Tamburella, A., Petrosino, S., Leggio, G. M., Di Marzo, V., & Drago, F. (2010). Enhanced cognitive performance of dopamine D3 receptor "knock‐out" mice in the step‐through passive‐avoidance test: Assessing the role of the endocannabinoid/endovanilloid systems. Pharmacological Research, 61, 531–536. https://doi.org/10.1016/j.phrs.2010.02.003
Millan, M. J., Di Cara, B., Dekeyne, A., Panayi, F., De Groote, L., Sicard, D., Cistarelli, L., Billiras, R., & Gobert, A. (2007). Selective blockade of dopamine D(3) versus D(2) receptors enhances frontocortical cholinergic transmission and social memory in rats: A parallel neurochemical and behavioural analysis. Journal of Neurochemistry, 100, 1047–1061. https://doi.org/10.1111/j.1471‐4159.2006.04262.x
Mutti, V., Bono, F., Tomasoni, Z., Bontempi, L., Guglielmi, A., Bolognin, S., Schwamborn, J. C., Missale, C., & Fiorentini, C. (2022). Structural plasticity of dopaminergic neurons requires the activation of the D3R‐nAChR heteromer and the PI3K‐ERK1/2/Akt‐induced expression of c‐Fos and p70S6K signaling pathway. Molecular Neurobiology, 59, 2129–2149. https://doi.org/10.1007/s12035‐022‐02748‐z
Neill, J. C., Grayson, B., Kiss, B., Gyertyán, I., Ferguson, P., & Adham, N. (2016). Effects of cariprazine, a novel antipsychotic, on cognitive deficit and negative symptoms in a rodent model of schizophrenia symptomatology. European Neuropsychopharmacology, 26, 3–14. https://doi.org/10.1016/j.euroneuro.2015.11.016
Palmeri, A., Privitera, L., Giunta, S., Loreto, C., & Puzzo, D. (2013). Inhibition of phosphodiesterase‐5 rescues age‐related impairment of synaptic plasticity and memory. Behavioral Brain Research, 240, 11–20. https://doi.org/10.1016/j.bbr.2012.10.060
Palmeri, A., Ricciarelli, R., Gulisano, W., Rivera, D., Rebosio, C., Calcagno, E., Tropea, M. R., Conti, S., Das, U., Roy, S., Pronzato, M. A., Arancio, O., Fedele, E., & Puzzo, D. (2017). Amyloid‐β peptide is needed for cGMP‐induced long‐term potentiation and memory. The Journal of Neuroscience, 37(29), 6926–6937. https://doi.org/10.1523/jneurosci.3607‐16.2017
Ripoli, C., Cocco, S., Li Puma, D. D., Piacentini, R., Mastrodonato, A., Scala, F., Puzzo, D., D'Ascenzo, M., & Grassi, C. (2014). Intracellular accumulation of amyloid‐β (Aβ) protein plays a major role in Aβ‐induced alterations of glutamatergic synaptic transmission and plasticity. The Journal of Neuroscience, 34, 12893–12903. https://doi.org/10.1523/JNEUROSCI.1201‐14.2014
Robinson, S. W., & Caron, M. G. (1997). Selective inhibition of adenylyl cyclase type V by the dopamine D3 receptor. Molecular Pharmacology, 52, 508–514. https://doi.org/10.1124/mol.52.3.508
Shohamy, D., & Wimmer, G. E. (2013). Dopamine and the cost of aging. Nature Neuroscience, 16, 519–521. https://doi.org/10.1038/nn.3385
Sigala, S., Missale, C., & Spano, P. (1997). Opposite effects of dopamine D2 and D3 receptors on learning and memory in the rat. European Journal of Pharmacology, 336, 107–112. https://doi.org/10.1016/s0014‐2999(97)01235‐1
Sokoloff, P., & Le Foll, B. (2017). The dopamine D3 receptor, a quarter century later. The European Journal of Neuroscience, 45, 2–19. https://doi.org/10.1111/ejn.13390
Sokoloff, P., Leriche, L., Diaz, J., Louvel, J., & Pumain, R. (2013). Direct and indirect interactions of the dopamine D₃ receptor with glutamate pathways: Implications for the treatment of schizophrenia. Naunyn Schmiedebergs Archives of Pharmacology, 386, 107–124. https://doi.org/10.1007/s00210‐012‐0797‐0
Swant, J., Stramiello, M., & Wagner, J. J. (2008). Postsynaptic dopamine D3 receptor modulation of evoked IPSCs via GABA(a) receptor endocytosis in rat hippocampus. Hippocampus, 18, 492–502. https://doi.org/10.1002/hipo.20408
Swant, J., & Wagner, J. J. (2006). Dopamine transporter blockade increases LTP in the CA1 region of the rat hippocampus via activation of the D3 dopamine receptor. Learning & Memory, 13, 161–167. https://doi.org/10.1101/lm.63806
Teich, A. F., Nicholls, R. E., Puzzo, D., Fiorito, J., Purgatorio, R., Fa', M., & Arancio, O. (2015). Synaptic therapy in Alzheimer's disease: A CREB‐centric approach. Neurotherapeutics, 12, 29–41. https://doi.org/10.1007/s13311‐014‐0327‐5
Torrisi, S. A., Salomone, S., Geraci, F., Caraci, F., Bucolo, C., Drago, F., & Leggio, G. M. (2017). Buspirone counteracts MK‐801‐induced schizophrenia‐like phenotypes through dopamine D3 receptor blockade. Frontiers in Pharmacology, 8, 710. https://doi.org/10.3389/fphar.2017.00710
Tropea, M. R., Li Puma, D. D., Melone, M., Gulisano, W., Arancio, O., Grassi, C., Conti, F., & Puzzo, D. (2021). Genetic deletion of α7 nicotinic acetylcholine receptors induces an age‐dependent Alzheimer's disease‐like pathology. Progress in Neurobiology, 206, 102154. https://doi.org/10.1016/j.pneurobio.2021.102154
Tropea, M. R., Sanfilippo, G., Giannino, F., Davì, V., Gulisano, W., & Puzzo, D. (2022). Innate preferences affect results of object recognition task in wild type and Alzheimer's disease mouse models. Journal of Alzheimer's Disease, 85, 1343–1356. https://doi.org/10.3233/JAD‐215209
Tropea, M. R., Torrisi, A., Vacanti, V., Pizzone, D., Puzzo, D., & Gulisano, W. (2022). Application of 3D printing technology to produce hippocampal customized guide cannulas. eNeuro, 9, 1–12. https://doi.org/10.1523/ENEURO.0099‐22.2022
Wang, S. H., Redondo, R. L., & Morris, R. G. (2010). Relevance of synaptic tagging and capture to the persistence of long‐term potentiation and everyday spatial memory. Proceedings of the National Academy of Sciences U S A, 107, 19537–19542. https://doi.org/10.1073/pnas.1008638107
Watson, D. J., Loiseau, F., Ingallinesi, M., Millan, M. J., Marsden, C. A., & Fone, K. C. (2012). Selective blockade of dopamine D3 receptors enhances while D2 receptor antagonism impairs social novelty discrimination and novel object recognition in rats: A key role for the prefrontal cortex. Neuropsychopharmacology, 37, 770–786. https://doi.org/10.1038/npp.2011.254
Xing, B., Meng, X., Wei, S., & Li, S. (2010). Influence of dopamine D3 receptor knockout on age‐related decline of spatial memory. Neuroscience Letters, 481, 149–153. https://doi.org/10.1016/j.neulet.2010.06.071
Zarate, N., Intihar, T. A., Yu, D., Sawyer, J., Tsai, W., Syed, M., Carlson, L., & Gomez‐Pastor, R. (2021). Heat shock factor 1 directly regulates postsynaptic scaffolding PSD‐95 in aging and Huntington's disease and influences striatal synaptic density. International Journal of Molecular Sciences, 22, 13113. https://doi.org/10.3390/ijms222313113
Zimnisky, R., Chang, G., Gyertyán, I., Kiss, B., Adham, N., & Schmauss, C. (2013). Cariprazine, a dopamine D(3)‐receptor‐preferring partial agonist, blocks phencyclidine‐induced impairments of working memory, attention set‐shifting, and recognition memory in the mouse. Psychopharmacology, 226, 91–100. https://doi.org/10.1007/s00213‐012‐2896‐5