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. 2024 Sep 10;11(3):e99010022.
doi: 10.14440/jbm.2024.0027. eCollection 2024.

The neuronal density in the rostral pole of substantia nigra pars compacta in Wistar Albino rats from Rijswijk rats: A link to spike-wave seizures

Lidia M Birioukova  1 , Darya A Tsvetaeva  1 , Inna S Midzyanovskaya  1 , Vladimir V Raevsky  1 , Evgenia Sitnikova  1
Affiliations

The neuronal density in the rostral pole of substantia nigra pars compacta in Wistar Albino rats from Rijswijk rats: A link to spike-wave seizures

Lidia M Birioukova et al. J Biol Methods. .

Abstract

This study aimed to investigate the role of the nigrostriatal dopaminergic system in the modulation of absence epilepsy. Immunochemical analysis of the rostral pole of the substantia nigra pars compacta (SNpc) was conducted on 13 adult male Wistar Albino rats from Rijswijk rats. The rostral pole of the SNpc included the dorsal and lateral parts. The neuronal density in the dorsal part was higher than in the lateral part. The ratio of dopaminergic to non-dopaminergic neurons in the lateral part of the SNpc was 1:1, while in the dorsal part, it was around 1.9:1. All rats exhibited spontaneous spike-wave discharges (SWDs) on their electrocorticograms. SWDs are known to be a hallmark of absence seizures in both human patients and rat models. In this study, we found that the number and duration of SWDs were negatively correlated with dopaminergic and non-dopaminergic neurons only in the lateral part of the SNpc. However, in the dorsal part of the SNpc, no correlations were found between neuronal density and the severity of absence epilepsy. Our findings suggest that the lateral SNpc may be involved in modulating the severity of absence epilepsy in genetically prone subjects. This contributes to a better understanding of the role of the nigrostriatal dopaminergic system in the absence of epilepsy.

Keywords: Absence epilepsy; Electrocorticography; Spike-wave discharges; Substantia nigra pars compacta; Tyrosine hydroxylase; WAG/Rij.

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Conflict of interest statement

The authors declare no conflicts of interest.

Figures

Figure 1
Figure 1
Figure 1. Spontaneous SWDs recorded in WAG/Rij rats were visualized in the time and frequency domains using LabChart v8 software. Top: A three-channel epidural ECoG recording obtained from the left frontal, right frontal, and occipital cortical locations. High-voltage SWD in the left frontal ECoG channel is highlighted. Please note bilaterally symmetrical waveforms of SWDs. Bottom: The power spectrum of the frontal left ECoG, in which the SWDs is highlighted.
Figure 2
Figure 2
The cytomorphological analysis of the SNpc in rat brain slices. Brain slices were immunohistochemically stained with antibodies to TH and counterstained with cresyl violet (Nissl staining). (A) The schematic representation of brain slice obtained at the level of −5.20 mm from bregma. At this level, the SNpc included the dorsal part (SNCD) and the lateral part (SNL). The same abbreviations were used in Paxinos’s Rat Brain Atlas [47]. (B) Section of native brain slice in which SNCD was outlined in red and SNL outlined in blue. The insertion a shows the enlarged fragment of B, in which TH-positive neurons are stained in brown and TH-negative are counterstained with cresyl violet in blue. The insertion b shows the enlarged fragment of a, in which TH-positive and TH-negative neurons are indicated by arrows. SNpc: Substantia nigra pars compacta; SNCD: Substantia nigra compact part, dorsal tier; TH: Tyrosine hydroxylase; SNL: Substantia nigra lateral part.
Figure 3
Figure 3
Density of neurons as measured in dorsal and lateral parts of the rostral pole of SNpc. Raw data points display all data obtained (three slices per rat/side, n = 13 rats). The density of both TH-positive neurons (A) and TH-negative neurons (B) was significantly higher in the dorsal part of the SNpc than in the lateral part. *significant differences with P < 1 e−6. SNpc: Substantia nigra pars compacta; TH: Tyrosine hydroxylase.
Figure 4
Figure 4
Pearson analysis revealed correlations between neuronal density in the rostral pole of SNpc and the parameters of spike-wave discharges (n=13 rats). In this pole, the lateral and dorsal parts of the SNpc were immunohistochemical-visualized for tyrosine hydroxylase and analyzed. Neuronal density (x-axis) refers to the number of neurons packed into a specific area of the SNpc. The correlation coefficients and P-values are shown above each corresponding plot. SNpc: Substantia nigra pars compacta.
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