Effect of lithium in hippocampal pyramidal neurons

OSSANI G.P; UCEDA A.M:; PONZO O.J.; LAGO N.R.; RIUDAVETS M; MARTINO D.J.

Congreso; Reunión anual de Sociedades Biocientíficas,; 2019

Lithium (Li) is a first-line drug for long-term prophylactic treatment of bipolar disorder (BD). However, mechanisms by which lithium exerts its mood-stabilizing effects are not very clear. A decrease in the overall volume of the hippocampus (H) by imaging studies has been described in patients with BD, it has also been reported that treatment with Li would reverse this effect, highlighting its neuroprotective effect. The aim of this work was to evaluate the effect of Li on pyramidal neurons within Cornu Ammonis (CA) subregions of the H. Wistar male rats (n=16) were randomized into two groups: control group (CG) fed ad libitum powered standard diet and experimental group (EG) fed ad libitum the same diet supplemented with 60 mmol of lithium/kg diet for 1 month. Lithium serum levels were measured and reached therapeutic values in EG (0.57±0.18 mmol/L). The brains were removed for histopathological analysis, fixed, and cut coronally. From each brain we selected a section (Bregma -2.8 mm) and stained with cresyl violet. First, we took serial pictures of the entire CA region with a 60x objective starting at the midline (CA1-2-3). Serial photos were divided into 4 groups, and the first 5 photos from each of them were selected for the analysis. Then, using the Image J Software we measured the area of the cell body and nucleus of CA pyramidal neurons on each selected picture. The criteria for selecting neurons to be measured included a well-defined nucleus and nucleolus. All assessments were performed blinded to Li treatment. We observed that the mean size (μm2) of the neuronal soma and nucleus of pyramidal neurons in the third group were significantly larger: CG=140±24 vs EG=174±36, t=-2.15, p=0.049 for cytoplasm; and CG=75±12 vs EG=92±16; t=-2.28, p=0.038 for nuclear size. This sub-region could correspond to CA2 subfield. Our results support the theory that lithium acts at the H level producing an increase of the cell and nuclear area of the pyramidal neurons in a specific sub-region of the CA.