Age and Lead Neurotoxicity: A Literature Review

Introduction: Lead exposure has adverse effects on the brain but their characteristics and severity vary by age. Damage is known to be critical in the prenatal period and infancy, better tolerated in adulthood, but again detrimental in old age.

Objective: To find, summarize, and systematize data on lead-induced damage to mammalian brain structures at different periods of life as a rationale for further development of therapeutic and preventive measures for humans.

Materials and methods: We searched for Russian and English-language publications issued in 1979–2024 in the PubMed archive of literature, Scopus abstract and citation database, eLibrary and CyberLeninka Russian scientific electronic libraries. The articles containing information on adverse effects of lead on the nervous system of laboratory animals were eligible for inclusion in the review. Of more than 500 papers screened, we selected 40 full-text peer-reviewed publications, 28 of which were issued in the last five years.

Results: This literature review outlines age-specific effects of lead on the nervous system. It presents the most common effects and targets of lead toxicity and can serve as a starting point for the development of preventive measures against neurodegenerative conditions caused by this chemical.

Conclusion: Fetuses and infants are the most vulnerable to damaging effects of lead on the nervous system.

1. Arkhipov EV, Garipova RV, Strizhakov LA, Bobkova IN, Tairova N. Kidney damage caused by lead exposure: Historical aspects. Terapevticheskiy Arkhiv. 2022;94(6):777-780. (In Russ.) doi: 10.26442/00403660.2022.06.201557

2. Chukhlovina ML. [Lead and the nervous system.] Gigiena i Sanitariya. 1997;(5):39-42. (In Russ.)

3. Smith MR, Yevoo P, Sadahiro M, et al. Integrative bioinformatics identifies postnatal lead (Pb) exposure disrupts developmental cortical plasticity. Sci Rep. 2018;8(1):16388. doi: 10.1038/s41598-018-34592-4

4. Needleman HL, Gunnoe C, Leviton A, et al. Deficits in psychologic and classroom performance of children with elevated dentine lead levels. N Engl J Med. 1979;300(13):689-695. doi: 10.1056/NEJM197903293001301

5. Privalova LI, Katsnelson BA, Kuzmin SV, et al. The impact of the environmental lead exposure on the health and development of children in cooper-producing townships of the Middle Urals. Biosfera. 2010;2(4):554-565. (In Russ.) Accessed January 27, 2025. https://cyberleninka.ru/article/n/o-vliyanii-ekologicheski-obuslovlennoy-ekspozitsii-k-svintsu-na-zdorovie-i-razvitie-detey-v-promyshlennyh-gorodah-srednego-urala

6. Park JH, Seo JH, Hong YS, et al. Blood lead concentrations and attention deficit hyperactivity disorder in Korean children: A hospital-based case control study. BMC Pediatr. 2016;16(1):156. doi: 10.1186/s12887-016-0696-5

7. Kim S, Arora M, Fernandez C, Landero J, Caruso J, Chen A. Lead, mercury, and cadmium exposure and attention deficit hyperactivity disorder in children. Environ Res. 2013;126:105-110. doi: 10.1016/j.envres.2013.08.008

8. Wright JP, Lanphear BP, Dietrich KN, et al. Developmental lead exposure and adult criminal behavior: A 30-year prospective birth cohort study. Neurotoxicol Teratol. 2021;85:106960. doi: 10.1016/j.ntt.2021.106960

9. Ishitsuka K, Yamamoto-Hanada K, Yang L, et al. Association between blood lead exposure and mental health in pregnant women: Results from the Japan environment and children’s study. Neurotoxicology. 2020;79:191-199. doi: 10.1016/j.neuro.2020.06.003

10. Cai H, Xu X, Zhang Y, Cong X, Lu X, Huo X. Elevated lead levels from e-waste exposure are linked to sensory integration difficulties in preschool children. Neurotoxicology. 2019;71:150-158. doi: 10.1016/j.neuro.2019.01.004

11. Beckwith TJ, Dietrich KN, Wright JP, Altaye M, Cecil KM. Reduced regional volumes associated with total psychopathy scores in an adult population with childhood lead exposure. Neurotoxicology. 2018;67:1-26. doi: 10.1016/j.neuro.2018.04.004

12. Zhang N, Baker HW, Tufts M, Raymond RE, Salihu H, Elliott MR. Early childhood lead exposure and academic achievement: Evidence from Detroit public schools, 2008–2010. Am J Public Health. 2013;103(3):e72-e77. doi: 10.2105/AJPH.2012.301164

13. Skerfving S, Löfmark L, Lundh T, Mikoczy Z, Strömberg U. Late effects of low blood lead concentrations in children on school performance and cognitive functions. Neurotoxicology. 2015;49:114-120. doi: 10.1016/j.neuro.2015.05.009

14. Wright JP, Dietrich KN, Ris MD, et al. Association of prenatal and childhood blood lead concentrations with criminal arrests in early adulthood. PLoS Med. 2008;5(5):e101. doi: 10.1371/journal.pmed.0050101

15. Fuller-Thomson E, Deng Z. Could lifetime lead exposure play a role in limbic-predominant age-related TDP-43 encephalopathy (LATE)? J Alzheimers Dis. 2020;73(2):455-459. doi: 10.3233/JAD-190943

16. Chintapanti S, Pratap Reddy K, Sreenivasula Reddy P. Behavioral and neurochemical consequences of perinatal exposure to lead in adult male Wistar rats: Protective effect by Centella asiatica. Environ Sci Pollut Res Int. 2018;25(13):13173–13185. doi: 10.1007/s11356-018-1500-x

17. Hossain S, Bhowmick S, Jahan S, et al. Maternal lead exposure decreases the levels of brain development and cognition-related proteins with concomitant upsurges of oxidative stress, inflammatory response and apoptosis in the offspring rats. Neurotoxicology. 2016;56:150-158. doi: 10.1016/j.neuro.2016.07.013

18. Sukharenko HV, Prishchepa IV, Nedzvetsky VS, Maksi mov VI. Rat brain cytoskeleton of astrocytes state in the early postnatal development following low dose Pb2+ ions exposure. Rossiyskiy Veterinarnyy Zhurnal. Sel’skokhozyaystvennye Zhivotnye. 2015;(2):10-13. (In Russ.)

19. Bakulski KM, Dou JF, Thompson RC, et al. Single-cell analysis of the gene expression effects of developmental lead (Pb) exposure on the mouse hippocampus. Toxicol Sci. 2020;176(2):396-409. doi: 10.1093/toxsci/kfaa069

20. Baranowska-Bosiacka I, Falkowska A, Gutowska I, et al. Glycogen metabolism in brain and neurons – astrocytes metabolic cooperation can be altered by pre- and neonatal lead (Pb) exposure. Toxicology. 2017;390:146-158. doi: 10.1016/j.tox.2017.09.007

21. Wang XM, Liu WJ, Zhang R, Zhou YK. Effects of exposure to low-level lead on spatial learning and memory and the expression of mGluR1, NMDA receptor in different developmental stages of rats. Toxicol Ind Health. 2013;29(8):686-696. doi: 10.1177/0748233712436641

22. Latronico T, Fasano A, Fanelli M, et al. Lead exposure of rats during and after pregnancy induces anti-myelin proteolytic activity: A potential mechanism for lead-induced neurotoxicity. Toxicology. 2022;472:153179. doi: 10.1016/j.tox.2022.153179

23. Ahmad F, Salahuddin M, Alamoudi W, Acharya S. Dysfunction of cortical synapse-specific mitochondria in developing rats exposed to lead and its amelioration by ascorbate supplementation. Neuropsychiatr Dis Treat. 2018;14:813-824. doi: 10.2147/NDT.S148248

24. Gąssowska M, Baranowska-Bosiacka I, Moczydłowska J, et al. Perinatal exposure to lead (Pb) induces ultrastructural and molecular alterations in synapses of rat offspring. Toxicology. 2016;373:13-29. doi: 10.1016/j.tox.2016.10.014

25. Rao Barkur R, Bairy LK. Evaluation of passive avoidance learning and spatial memory in rats exposed to low levels of lead during specific periods of early brain development. Int J Occup Med Environ Health. 2015;28(3):533-544. doi: 10.13075/ijomeh.1896.00283

26. Eremenko IR, Vasilyeva EV, Ryzhavsky BYa, Demidov OV. The effect of lead in milk period in lipid concentration on the cerebral hemispheres and cerebellum in the prepubertal rat ontogeny. Dal’nevostochnyy Meditsinskiy Zhurnal. 2013;(3):108-111. (In Russ.)

27. Dominguez S, Flores-Montoya MG, Sobin C. Early chronic exposure to low-level lead alters total h ippocampal microglia in pre-adolescent mice. Toxicol Lett. 2019;302:75-82. doi: 10.1016/j.toxlet.2018.10.016

28. Masoud AM, Bihaqi SW, Machan JT, Zawia NH, Renehan WE. Early-life exposure to lead (Pb) alters the expression of microRNA that target proteins associated with Alzheimer's disease. J Alzheimers Dis. 2016;51(4):1257-1264. doi: 10.3233/JAD-151018

29. Rahman A, Khan KM, Rao MS. Exposure to low level of lead during preweaning period increases metallothionein-3 expression and dysregulates divalent cation levels in the brain of young rats. Neurotoxicology. 2018;65:135-143. doi: 10.1016/j.neuro.2018.02.008

30. Rahman A, Khan KM, Al-Khaledi G, Khan I, Al-Shemary T. Over activation of hippocampal serine/threonine protein phosphatases PP1 and PP2A is involved in lead-induced deficits in learning and memory in young rats. Neurotoxicology. 2012;33(3):370-383. doi: 10.1016/j.neuro.2012.02.014

31. Sosedova LM, Kapustina EA, Vokina VA. The influence of the lead intoxication of male albino rats on the functioning of the nervous system of their offspring. Gigiena i Sanitariya. 2018;97(10):972-975. (In Russ.) doi: 10.18821/0016-9900-2018-97-10-972-975

32. Bihaqi SW, Bahmani A, Subaiea GM, Zawia NH. Infantile exposure to lead and late-age cognitive decline: Relevance to AD. Alzheimers Dement. 2014;10(2):187-195. doi: 10.1016/j.jalz.2013.02.012

33. Hsu CY, Chuang YC, Chang FC, Chuang HY, Chiou TT, Lee CT. Disrupted sleep homeostasis and altered expressions of clock genes in rats with chronic lead exposure. Toxics. 2021;9(9):217. doi: 10.3390/toxics9090217

34. Ouyang L, Zhang W, Du G, et al. Lead exposure-induced cognitive impairment through RyR-modulating intracellular calcium signaling in aged rats. Toxicology. 2019;419:55-64. doi: 10.1016/j.tox.2019.03.005

35. Zhu G, Fan G, Feng C, et al. The effect of lead exposure on brain iron homeostasis and the expression of DMT1/ FP1 in the brain in developing and aged rats. Toxicol Lett. 2013;216(2-3):108-123. doi: 10.1016/j.toxlet.2012.11.024. Erratum in: Toxicol Lett. 2013;218(3):308.

36. Voronin DM, Voronina EG. Features of child’s nervous system development. Sovremennye Zdorov’esberegayushchie Tekhnologii. 2016;(4(5)):57-75. (In Russ.)

37. Matović V, Buha A, Đukić-Ćosić D, Bulat Z. Insight into the oxidative stress induced by lead and/or cadmium in blood, liver and kidneys. Food Chem Toxicol. 2015;78:130-140. doi: 10.1016/j.fct.2015.02.011

38. Ryabova YuV, Kungurtseva AK, Petrunina EM, et al. Changes in health effects of lead exposure caused by exercise and the impact of biological prophylaxis on rats’ central nervous system. Meditsina Truda i Ekologiya Cheloveka. 2024;(2):191-210. (In Russ.) doi: 10.24412/2411-3794-2024-10213

39. Gundacker C, Fröhlich S, Graf-Rohrmeister K, et al. Perinatal lead and mercury exposure in Austria. Sci Total Environ. 2010;408(23):5744-5749. doi: 10.1016/j.scitotenv.2010.07.079

40. Dórea JG. Environmental exposure to low-level lead (Pb) co-occurring with other neurotoxicants in early life and neurodevelopment of children. Environ Res. 2019;177:108641. doi: 10.1016/j.envres.2019.108641