PMID- 29696534 OWN - NLM STAT- MEDLINE DCOM- 20190508 LR - 20190508 IS - 1559-0720 (Electronic) IS - 0163-4984 (Linking) VI - 187 IP - 1 DP - 2019 Jan TI - Ascorbic Acid Attenuates Lead-Induced Alterations in the Synapses in the Developing Rat Cerebellum. PG - 142-150 LID - 10.1007/s12011-018-1354-6 [doi] AB - We evaluated the effect of lead (Pb) and ascorbic acid treatment of pregnant female rats on cerebellar development in pups. Pb was administered in drinking water (0.2% Pb acetate), and ascorbic acid (100 mg/kg) was administered through oral intubation. Fifteen female rats were randomly classified into control, Pb, and Pb plus ascorbic acid (PA) groups. The treatment of Pb and ascorbic acid treatments were terminated after birth to evaluate the effects on the gestational development of the cerebellum. At postnatal day 21 (PND21), pups were sacrificed, and blood Pb level was analyzed. Blood Pb levels of pups and dams were highest in the Pb group and reduced in the PA group. Immunohistochemistry and immunoblot assays were conducted to study the cerebellar expression levels of synaptic proteins. Along with a significant reduction in Purkinje cells, the reduction in presynaptic (synaptophysin) and postsynaptic (postsynaptic density protein 95, N-methyl-D-aspartate receptor subtype 1) marker proteins was observed in Pb-exposed pups. Ascorbic acid treatment significantly prevented Pb-induced impairment in the cerebellar synaptic proteins. Hypothesizing that brain-derived neurotrophic factor (BDNF) might be affected by Pb exposure given its importance in the regulation of synaptogenesis, we observed a Pb-induced decrease and ascorbic acid-mediated increase of BDNF in the cerebellum. Luxol fast blue staining and myelin basic protein analysis suggest that ascorbic acid treatment ameliorated the Pb exposure-induced reduction in the axonal fibers in the developing cerebellum. Overall, we conclude that ascorbic acid treatment during pregnancy can prevent Pb-induced impairments in the cerebellar development in rats. FAU - Nam, Sung Min AU - Nam SM AD - Department of Anatomy, College of Veterinary Medicine, Konkuk University, 120 Neungdong-ro, Gwangjin-gu, Seoul, 05030, Republic of Korea. AD - College of Veterinary Medicine and Veterinary Science Research Institute, Konkuk University, Seoul, 05030, Republic of Korea. FAU - Cho, In-Sun AU - Cho IS AD - Department of Anatomy, College of Veterinary Medicine, Konkuk University, 120 Neungdong-ro, Gwangjin-gu, Seoul, 05030, Republic of Korea. AD - Korea Bio-Safety Institute Co. Ltd, Eumseong, Chungbuk, 27600, Republic of Korea. FAU - Seo, Jin Seok AU - Seo JS AD - Department of Anatomy, College of Veterinary Medicine, Konkuk University, 120 Neungdong-ro, Gwangjin-gu, Seoul, 05030, Republic of Korea. FAU - Go, Tae-Hun AU - Go TH AD - Department of Anatomy, College of Veterinary Medicine, Konkuk University, 120 Neungdong-ro, Gwangjin-gu, Seoul, 05030, Republic of Korea. FAU - Kim, Ji-Hye AU - Kim JH AD - Department of Rehabilitation Psychology, Seoul Rehabilitation Hospital, Seoul, 03428, Republic of Korea. FAU - Nahm, Sang-Soep AU - Nahm SS AD - Department of Anatomy, College of Veterinary Medicine, Konkuk University, 120 Neungdong-ro, Gwangjin-gu, Seoul, 05030, Republic of Korea. AD - College of Veterinary Medicine and Veterinary Science Research Institute, Konkuk University, Seoul, 05030, Republic of Korea. FAU - Chang, Byung-Joon AU - Chang BJ AD - Department of Anatomy, College of Veterinary Medicine, Konkuk University, 120 Neungdong-ro, Gwangjin-gu, Seoul, 05030, Republic of Korea. bjchang@konkuk.ac.kr. AD - College of Veterinary Medicine and Veterinary Science Research Institute, Konkuk University, Seoul, 05030, Republic of Korea. bjchang@konkuk.ac.kr. FAU - Lee, Jong-Hwan AU - Lee JH AD - Department of Anatomy, College of Veterinary Medicine, Konkuk University, 120 Neungdong-ro, Gwangjin-gu, Seoul, 05030, Republic of Korea. jhlee21@konkuk.ac.kr. AD - College of Veterinary Medicine and Veterinary Science Research Institute, Konkuk University, Seoul, 05030, Republic of Korea. jhlee21@konkuk.ac.kr. LA - eng PT - Journal Article DEP - 20180426 PL - United States TA - Biol Trace Elem Res JT - Biological trace element research JID - 7911509 RN - 2P299V784P (Lead) RN - PQ6CK8PD0R (Ascorbic Acid) SB - IM MH - Administration, Oral MH - Animals MH - Animals, Newborn MH - Ascorbic Acid/administration & dosage/*pharmacology MH - Cerebellum/*drug effects/*growth & development/metabolism MH - Female MH - Lead/administration & dosage/*toxicity MH - Male MH - Pregnancy MH - Rats MH - Rats, Sprague-Dawley MH - Synapses/*drug effects/metabolism OTO - NOTNLM OT - Ascorbic acid OT - Cerebellum OT - Lead (Pb) OT - NMDAR1 OT - PSD95 OT - Synaptophysin EDAT- 2018/04/27 06:00 MHDA- 2019/05/09 06:00 CRDT- 2018/04/27 06:00 PHST- 2018/03/12 00:00 [received] PHST- 2018/04/17 00:00 [accepted] PHST- 2018/04/27 06:00 [pubmed] PHST- 2019/05/09 06:00 [medline] PHST- 2018/04/27 06:00 [entrez] AID - 10.1007/s12011-018-1354-6 [pii] AID - 10.1007/s12011-018-1354-6 [doi] PST - ppublish SO - Biol Trace Elem Res. 2019 Jan;187(1):142-150. doi: 10.1007/s12011-018-1354-6. Epub 2018 Apr 26.