Taurine Neuroprotection and Neurogenesis Effect in Chronic Ethanol-Induced Rats

Abstract

Taurine (2-aminoethanesulfonic acid) is a non-protein β-amino acid essential for cellular homeostasis, with antioxidant, anti-inflammatory, and cytoprotective properties that are crucial for life maintenance. This study aimed to evaluate the effects of taurine administration on hippocampal neurogenesis, neuronal preservation, or reverse damage in rats exposed to forced ethanol consumption in an animal model. Wistar rats were treated with ethanol (EtOH) for a 28-day period (5% in the 1st week, 10% in the 2nd week, and 20% in the 3rd and 4th weeks). Two taurine treatment protocols (300 mg/kg i.p.) were implemented: one during ethanol consumption to analyze neuroprotection, and another after ethanol consumption to assess the reversal of ethanol-induced damage. Overall, the results demonstrated that taurine treatment was effective in protecting against deficits induced by ethanol consumption in the dentate gyrus. The EtOH+TAU group showed a significant increase in cell proliferation (145.8%) and cell survival (54.0%) compared to the EtOH+Sal group. The results also indicated similar effects regarding the reversal of ethanol-induced damage 28 days after the cessation of ethanol consumption. The EtOH+TAU group exhibited a significant increase (41.3%) in the number of DCX-immunoreactive cells compared to the EtOH+Sal group. However, this amino acid did not induce neurogenesis in the tissues of healthy rats, implying that its activity may be contingent upon post-injury stimuli.

Keywords: ethanol consumption; hippocampus; neurogenesis; neuroprotection; taurine.

Figure 1

Experimental protocol of taurine neuroprotection effect on chronic consumption ethanol.

Figure 2

Experimental protocol for the taurine effect on neuronal damage induced by chronic ethanol consumption.

Figure 3

Hippocampal cell volume and pyknotic cell. (GCL): granular cell layer, (SGL): subgranular zone. Arrows indicate pyknotic cells (cell death) (400× magnification).

Figure 4

Hippocampal volume profile after chronic ethanol ingestion and taurine (300 mg/kg, i.p) (n = 6). * p < 0.05 vs. H₂O/saline, ** p < 0.01 vs. H₂O/saline, *** p < 0.001 vs. H₂O/saline.

Figure 5

Effect of taurine on hippocampal neuroprotection: (I) number of Ki-67 profiles in the dentate gyrus of rats submitted to chronic ethanol consumption (n = 6). (B). * p < 0.05 vs. H₂O/saline, *** p < 0.001 vs. H₂O/saline, # p < 0.05 vs. EtOH/saline, ## p < 0.01 vs. EtOH/saline, ### p < 0.001 vs. EtOH/saline; (II) pattern of labeling of Ki-67 in the dentate gyrus of rats submitted to chronic ethanol consumption: (A) H₂O/saline group, (B) EtOH/saline group, (C) H₂O/TAU group, and (D) EtOH/TAU group. (CCG): granular cell layer; (ZSG): subgranular zone. Arrows indicate the Ki-67 immunoreactive cells. Calibration bar: 50 µm.

Figure 6

Effect of taurine on hippocampal neuroprotection. (I) BrdU number profile of immunoreactive cells in the dentate gyrus of rats subjected to chronic ethanol consumption (n = 6). * p < 0.05 vs. H₂O/saline, *** p < 0.001 vs. H₂O/saline, ## p < 0.01 vs. EtOH/saline, ### p < 0.001 vs. EtOH/saline $ p < 0.05 vs. EtOH/TAU. (II) Pattern of labeling with BrdU in the dentate gyrus of rats subjected to chronic ethanol consumption. (A)—H₂O/saline group; (B)—EtOH/saline group; (C)—H₂O/TAU group; and (D)—EtOH/TAU group. CCG—granular cell layer; ZSG—subgranular zone. Arrows indicate BrdU immunoreactive cells. Calibration bar: 50 µm.

Figure 7

Effects of taurine administration on cell death in the hippocampus of rats subjected to chronic ethanol consumption (n = 6). * p < 0.05 vs. H₂O+Sal, ** p < 0.01 vs. H₂O+Sal, *** p < 0.001 vs. H₂O+Sal, ## p < 0.01 vs. EtOH+Sal, ### p < 0.001 vs. EtOH+Sal.

Figure 8

Effect of taurine administration in the hippocampus volume on the reversion of damage in rats induced by chronic ethanol consumption experiment (n = 6). (I). Hippocampal volume; (II) cell proliferation—Ki67. * p < 0.05 vs. H₂O/saline, ** p < 0.01 vs. H₂O/saline, $ p < 0.05 vs. EtOH/TAU, $$$ p < 0.001 vs. EtOH/TAU.

Figure 9

Taurine neuroprotection. The peripheral inflammation caused by alcohol intake increases proinflammatory cytokines that cross the BBB to the CNS. The alcohol in the CNS promotes apoptosis and neuronal damage via the caspase pathway. Alcohol ingestion also activates the expression of Toll-like receptor 4 (TLR-4), increasing the inflammatory cytokines that potentiate the neuronal necrosis caused by ROS produced by NADPH-dependent oxidase (NOX), NOX gp91^phox expression, and increasing pyknotic cells. Taurine inhibits peripheral inflammation, neuronal damage, and death (adapted from [11], created with biorender).