Impact of Pseudomonas aeruginosa, Bacillus subtilis, Staphylococcus aureus, and Escherichia coli Oral Infusions on Cognitive Memory Decline in Mild Cognitive Impairment

Murugan Mukilan

doi:10.18006/2023.11(3).581.592

Authors

Murugan Mukilan Post-Doctoral Fellow, Advanced Technology Development Centre, Indian Institute of Technology, Kharagpur 721 302, West Bengal, India

DOI:

https://doi.org/10.18006/2023.11(3).581.592

Keywords:

Learning, Memory, Bacillus subtilis, Staphylococcus aureus, Escherichia coli, Pseudomonas aeruginosa, Cognitive decline

Abstract

Synaptic plasticity is a result of changes in the neuronal circuits which may result in the formation of protein-dependent (long-term memory (LTM) formation) and protein-independent (short-term memory (STM) formation) memories. This STM formation is based on existing proteins, but LTM formation depends on RNA and protein synthesis within the neuronal cells. This RNA and protein synthesis may depend on stimulus exposure like odour, taste, and other environmental stimuli. The present study is aimed to show the impact of oral bacterial infusions on cognitive memory formation through pre and post-infusive behavioural analysis. The results of the study revealed that oral infusions of Pseudomonas aeruginosa, Bacillus subtilis, Staphylococcus aureus and Escherichia coli result in impaired cognitive learning and memory formation. This impaired cognitive memory formation is shown with the help of two-step (pre and post-infusive) behavioural analysis. Pre-infusive behavioural study shows no decline in cognitive learning and memory formation before oral microbial infusions in a serene habituated environment. After oral microbial infusions, a post-infusive behavioural analysis may reveal a memory decline in the treated group. Comparative two-step behavioural analysis indicates that P. aeruginosa infusions strongly impact cognitive memory decline compared to the other three groups. This cognitive memory decline may happen due to the production of primary/secondary metabolites within the animal gut and their transportation to the CNS through the blood-brain barrier. The outcome of the present study states that poor oral hygiene plays a significant role in cognitive memory decline concerning mild cognitive impairment (MCI).

Author Biography

Murugan Mukilan, Post-Doctoral Fellow, Advanced Technology Development Centre, Indian Institute of Technology, Kharagpur 721 302, West Bengal, India

Assistant Professor, Department of Biotechnology, Sri Ramakrishna College of Arts & Science, Coimbatore 641 006, Tamil Nadu, India

References

Abraham, W.C., & Robins, A. (2005). Memory retention – the synaptic stability versus plasticity dilemma. Trends in Neurosciences, 28, 73-78. DOI: https://doi.org/10.1016/j.tins.2004.12.003

Abraham, W.C., & Williams, J.M., (2008). LTP maintenance and its protein synthesis-dependence. Neurobiology of Learning and Memory, 89, 260-268. DOI: https://doi.org/10.1016/j.nlm.2007.10.001

Agus, A., Planchais, J., & Sokol, H. (2018). Gut Microbiota Regulation of Tryptophan Metabolism in Health and Disease. Cell Host & Microbe, 23, 716-724. DOI: https://doi.org/10.1016/j.chom.2018.05.003

Alberini, C.M. (2008). The role of protein synthesis during the labile phases of memory: Revisitig the skepticism. Neurobiology of Learning and Memory, 89, 234 – 246. DOI: https://doi.org/10.1016/j.nlm.2007.08.007

Alberini, C.M. (2009). Transcription factors in long-term memory and synaptic plasticity. Physiological Reviews, 89, 121-145. DOI: https://doi.org/10.1152/physrev.00017.2008

Baj, A., Moro, E., Bistoletti, M., Orlandi, V., et al. (2019). Glutamatergic Signaling Along The Microbiota-Gut-Brain-Axis. International Journal of Molecular Sciences, 20, 1482. DOI: https://doi.org/10.3390/ijms20061482

Balin, B.J., Gérard, H.C., Arking, E.J., Appelt, D.M., et al. (1998). Identification and localization of Chlamydia pneumoniae in the Alzheimer's brain. Medical Microbiology and Immunology 187, 23-42. DOI: https://doi.org/10.1007/s004300050071

Bauer, K.C., Huus, K.E., & Finlay, B.B. (2016). Microbes and the mind: emerging hallmarks of the gut microbiota-brain axis. Cellular microbiology, 18, 632 – 644. DOI: https://doi.org/10.1111/cmi.12585

Besnard, A., Galan-Rodriguez, B., Vanhoutte, P., & Caboche, J. (2011). Elk-1a transcription factor with multiple facets in the brain. Frontiers in Neuroscience, 5, 35. DOI: https://doi.org/10.3389/fnins.2011.00035

Bisaz, R., Travaglia, A., & Alberini, C.M. (2014). The neurobiological bases of memory formation: from physiological conditions to psychopathology. Psychopathology, 47, 347-356. DOI: https://doi.org/10.1159/000363702

Bo, T.B., Zhang, X.Y., Kohl, K.D., Wen, J., et al. (2020). Coprophagy prevention alters microbiome, metabolism, neurochemistry, and cognitive behavior in a small mammal. ISME Journal, 14, 2625-2645. DOI: https://doi.org/10.1038/s41396-020-0711-6

Byzitter, J., Lukowiak, K., Karnik, V., & Dalesman, S. (2012). Acute combined exposure to heavy metals (Zn, Cd) blocks memory formation in a freshwater snail. Ecotoxicology, 21, 860-868. DOI: https://doi.org/10.1007/s10646-011-0847-2

Cammann, D., Lu, Y., Cummings, M.L., Zhang, M.L., et al. (2023). Genetic correlations between Alzheimer's disease and gut microbiome genera. Scientific Reports 13, 5258. DOI: https://doi.org/10.1038/s41598-023-31730-5

Caspani, G., & Swann, J. (2019). Microbial metabolites involved in the signalling from microbiota to brain. Current Opinion in Pharmacology, 48, 99-106. DOI: https://doi.org/10.1016/j.coph.2019.08.001

Chen, D., Yang, X., Yang, J., Lai, G., et al. (2017). Prebiotic effect of fructooligosaccharides from Morinda officinalis on alzheimer's disease inrodent models by targeting the microbiota-gut-brain axis. Frontiers in Aging Neuroscience, 9, 403. DOI: https://doi.org/10.3389/fnagi.2017.00403

Chen, Y., Xu, J., & Chen, Y. (2021). Regulation of Neurotransmitters by the Gut Microbiota and Effects on Cognition in Neurological Disorders. Nutrients, 13, 2099. DOI: https://doi.org/10.3390/nu13062099

Cryan, J.F., & Dinan, T.G., (2012). Mind-altering microorganisms: the impact of the gut microbiota on brain and behaviour. Nature Reviews Neuroscience, 13, 701-712. DOI: https://doi.org/10.1038/nrn3346

Da, D., Zhao, Q., Zhang, H., Wu, W., et al. (2023). Oral microbiome in older adults with mild cognitive impairment. Journal of Oral Microbiology, 15, 2173544. DOI: https://doi.org/10.1080/20002297.2023.2173544

Davis, H.P., & Squire, L.R. (1984). Protein synthesis and memory: A review. Psychological bulletin, 96, 518-559. DOI: https://doi.org/10.1037/0033-2909.96.3.518

Dicks, L.M. (2022). Gut Bacteria and Neurotransmitters. Microorganisms, 10, 1838. DOI: https://doi.org/10.3390/microorganisms10091838

Dominy, S.D., Lynch, C., Ermini, F., Benedyk, M., et al. (2019). Porphyromonas gingivalis in Alzheimer's disease brains: Evidence for disease causation and treatment with small-molecule inhibitors. Science Advances, 5, eaau3333. DOI: https://doi.org/10.1126/sciadv.aau3333

Evans, H.T., Blackmore, D., Götz, J., & Bodea, L. (2021). De novo proteomic methods for examining the molecular mechanisms underpinning long-term memory. Brain Research Bulletin, 169, 94-103. DOI: https://doi.org/10.1016/j.brainresbull.2020.12.015

Fonseca, R., Vabulas, R.M., Hartl, F.U., Bonhoeffer, T., et al. (2006). A Balance of Protein Synthesis and Proteasome-Dependent Degradation Determines the Maintenance of LTP. Neuron, 52, 239-245. DOI: https://doi.org/10.1016/j.neuron.2006.08.015

Franco-Robles, E., & López, M. (2015). Implication of fructans in health: Immunomodulatory and antioxidant mechanisms. Scientific World Journal, 2015, 289267. DOI: https://doi.org/10.1155/2015/289267

Ganesh, A., Bogdanowicz, W., Balamurugan, K., Varman, D.R., & Rajan, K.E. (2012). Egr-1 antisense oligodeoxynucleotide administration into the olfactory bulb impairs olfactory learning in the greater short-nosed fruit bat Cynopterus sphinx. Brain Research, 1471, 33 – 45. DOI: https://doi.org/10.1016/j.brainres.2012.06.038

Ganesh, A., Bogdanowicz, W., Haupt, M., Marimuthu, G., & Rajan, K.E. (2010). Role of olfactory bulb serotonin in olfactory learning in the greater short-nosed fruit bat Cynopterus sphinx. Brain Research, 1352, 108-117. DOI: https://doi.org/10.1016/j.brainres.2010.06.058

Gao, K., Pi, Y., Mu, C.L., Farzi, A., et al. (2019). Increasing carbohydrate availability in the hindgut promotes hypothalamic neurotransmitter synthesis: Aromatic amino acids linking the microbiota-brain axis. Journal of Neurochemistry, 149, 641 – 659. DOI: https://doi.org/10.1111/jnc.14709

Gao, K., Pi, Y., Mu, C.L., Peng, Y., et al. (2018). Antibiotics-induced modulation of large intestinal microbiota altered aromatic amino acid profile and expression of neurotransmitters in the hypothalamus of piglets. Journal of Neurochemistry, 146, 219-234. DOI: https://doi.org/10.1111/jnc.14333

Gao, S.S., Chu, C.H., & Young, F.Y.F. (2020). Oral Health and Care for Elderly People with Alzheimer's Disease. International Journal of Environmental Research and Public Health, 17, 5713. DOI: https://doi.org/10.3390/ijerph17165713

Gérard, H.C., Dreses-Werringloer, U., Wildt, K.S., Deka, S., et al. (2006). Chlamydophila (Chlamydia) pneumoniae in the Alzheimer's brain. FEMS Immunology and Medical Microbiology, 48, 355-366. DOI: https://doi.org/10.1111/j.1574-695X.2006.00154.x

Giuffré, M., Moretti, R., Campisciano, G., da Silveria, M., et al. (2020). You Talking to Me? Says the Enteric Nervous System (ENS) to the Microbe. How Intestinal Microbes Interact with the ENS. Journal of Clinical Medicine, 9, 3705. DOI: https://doi.org/10.3390/jcm9113705

Heyck, M., & Ibarra, A., (2019). Microbiota and memory: a symbiotic therapy to counter cognitive decline? Brain Circulation, 5, 124-129. DOI: https://doi.org/10.4103/bc.bc_34_19

Hu, L., Zhu, S., Peng, X., Li, K., et al. (2020). High Salt Elicits Brain Inflammation and Cognitive Dysfunction, Accompanied by Alternations in the Gut Microbiota and Decreased SCFA production. Journal of Alzheimer's Disease, 77, 629-640. DOI: https://doi.org/10.3233/JAD-200035

Huang, H.K., Wang, J.H., Lei, W.Y., Chen, C.L., et al. (2018). Helicobacter pylori infection is associated with an increased risk of Parkinson's disease: a population-based retrospective cohort study. Parkinsonism & Related Disorders, 47, 26-31. DOI: https://doi.org/10.1016/j.parkreldis.2017.11.331

Igaz, L.M., Winograd, M., Cammarota, M., Izquierdo, L.A., et al. (2006). Early activation of extracellular signal-regulated kinase signaling pathway in the hippocampus is required for short-term memory formation of a fear-motivated learning. Cellular and Molecular Neurobiology, 26, 989-1002. DOI: https://doi.org/10.1007/s10571-006-9099-8

Jahn, H. (2013). Memory loss in Alzheimer's disease. Dialogues in Clinical Neuroscience, 15, 445 – 454. DOI: https://doi.org/10.31887/DCNS.2013.15.4/hjahn

Jameson, K.G., Olson, C.A., Kazmi, S.A., & Hsiao, E.Y. (2020). Toward Understanding Microbiome-Neuronal Signaling. Molecular Cell, 78, 577-583. DOI: https://doi.org/10.1016/j.molcel.2020.03.006

Jones, M.W., Errington, M.L., French, P.J., Bliss, T.V., et al. (2001). A requirement for the immediate early gene Zif268 in the expression of late LTP and long-term memories. Nature Neuroscience, 4, 289 – 296. DOI: https://doi.org/10.1038/85138

Kandel, E.R. (2001). The molecular biology of memory storage: A dialogue between genes and synapses. Science, 294, 1030-1038. DOI: https://doi.org/10.1126/science.1067020

Karen, C., Shyu, D.J.H., & Rajan, K.E. (2021). Lactobacillus paracasei Supplementation Prevents Early Life Stress-Induced Anxiety and Depressive-Like Behavior in Maternal Separation Model-Possible Involvement of Microbiota-Gut-Brain Axis in Differential Regulation of MicroRNA124a/132 and Glutamate Receptors. Frontiers in Neuroscience, 15, 719933. DOI: https://doi.org/10.3389/fnins.2021.719933

Lahner, E., Annibale, B., & DelleFave, G. (2009). Systematic review: Helicobacter pylori infection and impaired drug absorption. Alimentary pharmacology & Therapeutics, 29, 379-386. DOI: https://doi.org/10.1111/j.1365-2036.2008.03906.x

Li, H., Wang, P., Zhou, Y., Zhao, F., et al. (2022). Correlation between intestinal microbiotal imbalance and 5-HT metabolism, immune inflammation in chronic unpredictable mild stress male rats. Genes, Brain and Behavior, 21, e12806. DOI: https://doi.org/10.1111/gbb.12806

Lin, H., Chen, C., de Belle, J.S., Tully, T., & Chiang, A. (2021). CREB A and CREB B in two identified neurons gate long-term memory formation in Drosophila. Proceedings of the National Academy of Sciences of the United States of America, 118, e2100624118. DOI: https://doi.org/10.1073/pnas.2100624118

Liu, N., Sun, S., Wang, P., Sun, Y., et al. (2021). The mechanism of Secretion and Metabolism of Gut-Derived 5-Hydroxytryptamine. International Journal of Molecular Sciences, 22, 7931. DOI: https://doi.org/10.3390/ijms22157931

Liu, S., Butler, C.A., Ayton, S., Reynolds, E.C., et al. (2023). Porphyromonas gingivalis and the pathogenesis of Alzheimer's disease. Critical Reveiws in Microbiology, 4, 1-11. DOI: https://doi.org/10.1080/1040841X.2022.2163613

Lotz, S.K., Blackhurst, B.M., Reagin, K.L., & Funk, K.E. (2021). Microbial Infections Are a Risk Factor for Neurodegenerative Diseases. Frontiers in Cellular Neuroscience, 15, 691136. DOI: https://doi.org/10.3389/fncel.2021.691136

Luqman, A., Nega, M., Nguyen, M.T., Ebner, P., et al. (2018). SadA-Expressing Staphylococci in the Human Gut Show Increased Cell Adherence and Internalization. Cell Reports, 22, 535-545. DOI: https://doi.org/10.1016/j.celrep.2017.12.058

Markowiak-Kopeć, P., & Slizewska, K. (2020). The Effect of Probiotics on the Production of Short-Chain Fatty Acids by Human Internal Microbiome. Nutrients, 12, 1107. DOI: https://doi.org/10.3390/nu12041107

Martande, S.S., Pradeep, A.R., Singh, S.P., Kumari, M., et al. (2014). Periodontal health condition in patients with Alzheimer's disease. American Journal of Alzheimer's Disease & Other Dementias, 29, 498-502. DOI: https://doi.org/10.1177/1533317514549650

McGee, D.J, Lu, X.H., & Disbrow, E.A. (2018). Stomaching the possibility of a pathogenic role for Helicobacter pylori in Parkinson's disease. Journal of Parkinson's Disease, 8, 367-374. DOI: https://doi.org/10.3233/JPD-181327

Miyashita, T., Kikuchi, E., Horiuchi, J., & Saitoe, M. (2018). Long-Term Memory Engram Cells Are Established b c-Fos/CREB Transcriptional Cycling. Cell Reports, 25, 2716-2728. DOI: https://doi.org/10.1016/j.celrep.2018.11.022

Mohamed, H.A., Yao, W., Fioravante, D., Smolen, P.D., et al. (2005). cAMP-response Elements in Aplysia creb 1, creb2, and Ap-uch Promoters: IMPLICATIONS FOR FEEDBACK LOOPS MODULATING LONG TERM MEMORY. Journal of Biological Chemistry, 29, 27035-27043. DOI: https://doi.org/10.1074/jbc.M502541200

Mukilan, M. (2022). Effect of probiotics, Prebiotics and Synbiotic Supplementation on Cognitive Impairment: A Review. Journal of Experimental Biology and Agricultural Sciences, 10, 1-11. DOI: https://doi.org/10.18006/2022.10(1).1.11

Mukilan, M., Bogdanowicz, W., Marimuthu, G., & Rajan, K.E. (2018a). Odour discrimination learning in the Indian greater short-nosed fruit bat (Cynopterus sphinx): differential expression of Egr-1, C-fos and PP-1 in the olfactory bulb, amygdala and hippocampus. Journal of Experimental Biology, 221, jeb175364. DOI: https://doi.org/10.1242/jeb.175364

Mukilan, M., Rajathei, D.M., Jeyaraj, E., Kayalvizhi, N., & Rajan, K.E., (2018b). MiR-132 regulated olfactory bulb proteins linked to olfactory learning in greater short-nosed fruit bat Cynopterus sphinx. Gene, 671, 10-20. DOI: https://doi.org/10.1016/j.gene.2018.05.107

Murciano-Brea, J., Garcia-Montes, M., Geuna, S., Herrera-Rincon, C. (2021). Gut Microbiota and Neuroplasticity. Cells, 10, 2084. DOI: https://doi.org/10.3390/cells10082084

Murman, D.L. (2015). The impact of Age on Cognition (2015). Seminars in Hearing, 36, 111-121. DOI: https://doi.org/10.1055/s-0035-1555115

Narengaowa, Kong, W., Lan, F., Awan, U.F., Qing, H., et al. (2021). The Oral-Gut-Brain AXIS: The Influence of Microbes in Alzheimer's Disease. Frontiers in Cellular Neuroscience, 15, 633735. DOI: https://doi.org/10.3389/fncel.2021.633735

Nelson, C.D., Kim, M.J., Hsin, H., Chen, Y., et al. (2013). Phosphorylation of threonine-19 of PSD-95 by GSK-3β is required for PSD-95 mobilization and long-term depression. Journal of Neuroscience, 33, 12122-12135. DOI: https://doi.org/10.1523/JNEUROSCI.0131-13.2013

Neto, J., Jantsch, J., Rodrigues, F., Squizani, S., et al. (2023). Impact of cafeteria diet and n3 supplementation on the intestinal microbiota, fatty acids levels, neuroinflammatory markers and social memory in male rats. Physiology & Behavior, 260, 114068. DOI: https://doi.org/10.1016/j.physbeh.2022.114068

O'Donnell, M.P., Fox, B.W., Chao, P., Schroedr, F.C., et al. (2020). A neurotransmitter produced by gut bacteria modulates host sensory behaviour. Nature, 583, 415-420. DOI: https://doi.org/10.1038/s41586-020-2395-5

Olsen, I. (2021) Porphyromonas gingivalis-Induced Neuroinflammation in Alzheimer's Disease. Frontiers in Neuroscience, 15, 691016. DOI: https://doi.org/10.3389/fnins.2021.691016

Orr, M.E., Reveles, K.R., Yeh, C., Young, E.H., et al. (2020). Can oral health and oral-derived biospecimens predict progression of dementia? Oral Diseases, 26, 249-258. DOI: https://doi.org/10.1111/odi.13201

Philips, G.T., Ye, X., Kopec, A.M., & Carew, T.J. (2013). MAPK establishes a molecular context that defines effective training patterns for long-term memory formation. Journal of Neuroscience, 33, 7565-7573. DOI: https://doi.org/10.1523/JNEUROSCI.5561-12.2013

Rajan, K.E. (2021). Olfactory learning and memory in the greater short-nosed fruit bat Cynopterus sphinx: the influence of conspecifics distress calls. Journal of Comparative Physiology A, 207, 667-679. DOI: https://doi.org/10.1007/s00359-021-01505-2

Ribeiro, G.R., Costa, J.L., Ambrosano, G.M., & Garcia, R.C. (2012). Oral health of elderly with Alzheimer's disease. Oral Surgery, Oral Medicine, Oral Pathology and Oral Radiology, 114, 338-343. DOI: https://doi.org/10.1016/j.oooo.2012.03.028

Rosin, S., Xia, K., Andrea Azcarate-Peril, M., Carlson, A.L., et al. (2021). A preliminary study of Gut Microbiome Variation and HPA Axis Reactivity in Healthy Infants. Psychoneuroendocrinology, 124, 105046. DOI: https://doi.org/10.1016/j.psyneuen.2020.105046

Roux, C.M., Leger, M., & Freret, T. (2021). Memory Disorders Related to Hippocampal Function: The interest of 5-HT4 Rs Targeting. International Journal of Molecular Sciences, 22, 12082. DOI: https://doi.org/10.3390/ijms222112082

Ryder, M.I. (2022). The Link Between Periodontitis and Alzheimer's Disease: Reality or Yet Another Association. Current Oral Health Reports, 9, 157 – 166. DOI: https://doi.org/10.1007/s40496-022-00319-8

Sadaqat, Z., Kaushik, S., & Kain, P. (2021). Gut Feeding the Brain: Drosophila Gut an Animal Model for Medicine to Understand Mechanisms Mediating Food Preferences. Preclinical Animal Modeling in Medicine, Intech Open doi: 10.5772/intechopen.96503. DOI: https://doi.org/10.5772/intechopen.96503

Schafe, G.E., & LeDoux, J.E. (2000) Memory consolidation of auditory pavlovian fear conditioning requires protein synthesis and protein kinase A in the amygdala. Journal of Neuroscience, 20, RC96. DOI: https://doi.org/10.1523/JNEUROSCI.20-18-j0003.2000

Scharf, M.T., Woo, N.H., Lattal, K.M., Young, J.Z., Nguyen, P.V., & Abel, T. (2002). Protein synthesis is required for the enhancement of long-term potentiation and long-term memory by space training. Journal of Neurophysiology, 87, 2770-2777. DOI: https://doi.org/10.1152/jn.2002.87.6.2770

Seymour, T., & Zhang, J. (2022). Porphyromonas Gingivalis in the Pathogenesis of Alzheimer's Disease and Its Therapeutic Target. Journal of Exploratory Research in Pharmacology, 7, 45-53. DOI: https://doi.org/10.14218/JERP.2021.00030

Sharma, V.K., & Singh, T.G. (2020). CREB: A Multifaceted Target for Alzheimer's Disease. Current Alzheimer Research, 17, 1280-1293. DOI: https://doi.org/10.2174/1567205018666210218152253

Shoemark, D.K., & Allen, S.J. (2015). The microbiome and disease: Reviewing the links between the oral microbiome, aging and alzheimer's disease. Journal of Alzheimer's Disease, 43, 725-738. DOI: https://doi.org/10.3233/JAD-141170

Smart, T.G., & Paoletti P. (2012). Synaptic Neurotransmitter-Gated Receptors. Cold Spring Harbor Prespectives in Biology, 4, a009662. DOI: https://doi.org/10.1101/cshperspect.a009662

Strandwitz, P. (2018). Neurotransmitter modulation by the gut microbiota. Brain Research, 1693, 128-133. DOI: https://doi.org/10.1016/j.brainres.2018.03.015

Ticinesi, A., Tana, C., Nouvenne, A., Prati B., et al. (2018). Gut microbiota, cognitive fraility and dementia in older individuals: A systematic review. Clinical Interventions in Aging, 13, 1497-1511. DOI: https://doi.org/10.2147/CIA.S139163

van de Wouw, M., Boehme, M., Lyte, J.M., Wiley, N., Strain, C., et al. (2018). Short-chain fatty acids: Microbial metabolites that alleviate stress-induced brain-gut axis alterations. The Journal of Physiology, 596, 4923-4944. DOI: https://doi.org/10.1113/JP276431

Verhaar, B.J.H., Hendriksen, H.M.A., Leeuw, F.A. de, Doorduijn,

A.S., et al. (2022). Gut Microbiota Composition Is Related to AD Pathology. Frontiers in Immunology, 12, 794519. DOI: https://doi.org/10.3389/fimmu.2021.794519

Vinay, P., Karen, C., Balamurugan, K., & Rajan, K.E. (2021). Cronobacter sakazakii infection in Early Postnatal Rats Impaired Contextual-Associated Learning: a Putative Role of C5a-Mediated NF-ĸß and ASK1 Pathways. Journal of Molecular Neuroscience, 71, 28-41. DOI: https://doi.org/10.1007/s12031-020-01622-8

Wang, X., Pan, W., Xu, N., Zhou, Z., et al. (2019). Environmental enrichment improves long-term memory impairment and aberrant synaptic plasticity by BDNF/TrkB signaling in nerve-injured mice. Neuroscience Letters 694, 93-98. DOI: https://doi.org/10.1016/j.neulet.2018.11.049

Wong, C.B., Kobayashi, Y., & Xiao, J. (2018). Probiotics for preventing cognitive impairment in alzheimer's disease. In A. Evrensel, & B.O., Ǘnsalver (eds), Gut Microbiota, Intech Open. doi: 10.5772/intechopen.79088. DOI: https://doi.org/10.5772/intechopen.79088

Yano, J.M., Yu, K., Donaldson, G.P., Shastri, G.G., et al. (2015). Indigenous bacteria from the gut microbiota regulate host serotonin biosynthesis. Cell, 161, 264-276. DOI: https://doi.org/10.1016/j.cell.2015.02.047

Zhang, G., & Stackman Jr, RW, (2015). The role of serotonin 5-HT2A receptors in memory and cognition. Frontiers in Pharmacology, 6, 225. DOI: https://doi.org/10.3389/fphar.2015.00225

Zhang, Y., Zhu, M., Sun, Y., Tang, B., et al. (2020). Environmental noise degrades hippocampus-related learning and memory. Proceedings of the National Academy of Sciences of the United States of America, 118, e2017841117. DOI: https://doi.org/10.1073/pnas.2017841117