Modeling an ataxic phenotype induced by combined administration of 3-acetylpyridine and lipopolysaccharide

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Introduction

Spinocerebellar ataxias (SCA) are neurodegenerative disorders with autosomal dominant, autosomal recessive, or X-linked inheritance patterns. They often show population-specific characteristics and involve damage to the cerebellum and other regions of the nervous system [1–3]. The clinical manifestations of SCA range from isolated cerebellar syndromes, such as dysmetria, asynergia, and dysdiadochokinesia, to combined forms with extracerebellar involvement, including peripheral neuropathy, pigmentary retinopathy, and cognitive impairment [4–7].

Due to advances in diagnostic technologies, multiple clinical forms of the disease have been identified, with a current global prevalence of up to 6 cases per 100,000 people. Despite their relative rarity compared to other neurodegenerative diseases, SCAs are associated with severe and prolonged disability, imposing a significant burden on patients’ families as well as on healthcare systems [4, 8].

To date, the pathogenesis of most SCA types remains insufficiently understood. Although some common features can be observed, particularly at late stages of the disease, different forms of SCA involve distinct specific mechanisms [9].

Based on the nature of the molecular defect, SCAs can be divided into two groups: those caused by conventional structural variations and those attributed to microsatellite repeat expansions. Among the latter, the most common variants are associated with CAG repeat expansions, leading to the formation of toxic proteins with elongated polyglutamine tracts. In contrast, for non-coding expansions, RNA toxicity and associated mechanisms, including RAN translation, play a predominant role. In the case of conventional structural mutations, pathogenesis is more often driven by loss of protein function, including proteins involved in ion channel regulation and intracellular signaling pathways. Ultimately, all these mechanisms trigger disruption of calcium homeostasis and synaptic transmission, which in turn is associated with impaired afferent input to Purkinje cells and/or alterations in their intrinsic spontaneous activity [10–13].

Currently, there are numerous experimental models of SCA that successfully reproduce motor impairments. However, none of them fully captures the entire clinical picture of the disease. The need to simulate as many pathogenetic characteristics of SCA as possible has driven the development of combined in vivo models, which allow more accurate reproduction of the nonlinear interactions characteristic of human neurodegenerative diseases [14, 15].

Recently, particular attention has been drawn to inflammation in the cerebellum associated with glial activation. Accumulating evidence from both toxin-induced and genetic models indicates that neuroinflammation is a key process involved in both disease initiation and progression. Nevertheless, the use of combined approaches based on the combination of multiple pathogenic factors currently remains limited [16, 17].

In this context, we developed a combined model of the SCA phenotype that integrates the induction of a neuroinflammatory response via intracerebroventricular (ICV) administration of lipopolysaccharide (LPS) followed by intraperitoneal (IP) neurotoxic challenge with 3-acetylpyridine (3-AP).

Study aim: to assess the representativeness of the SCA model using a battery of behavioral tests.

Materials and methods

All experiments were conducted in compliance with bioethical standards for the use of laboratory animals, in accordance with the Recommendation No. 33 of the Council of the Eurasian Economic Commission dated November 14, 2023 “Guidelines for Handling Laboratory (Experimental) Animals in Preclinical (Non-Clinical) Studies”, as well as the Rules for Handling Laboratory Rodents and Rabbits (GOST 33216-2014). The study protocol was approved by the Ethics Committee of the Russian Center of Neurology and Neurosciences (Protocol No. 2-3/25 dated February 17, 2025). In accordance with the OECD “Guidance Document on the Recognition, Assessment, and Use of Clinical Signs as Humane Endpoints for Experimental Animals Used in Safety Evaluation (2002)”, the following criteria were selected as humane endpoints for the most probable conditions: rapid body weight loss (greater than 25% of baseline), a drop in body temperature of more than 10% relative to normal, evidence of organ failure, prolonged absence of response to external stimuli, respiratory distress, and severe dehydration.

The study was performed on male Wistar rats (n = 30) obtained from the Stolbovaya branch of the Center for Biomedical Technologies of the Federal Medical Biological Agency of Russia. The animals were 3.5 months old at the start of the experiment and weighed 300–320 g. They had undergone a two-week quarantine. The animals were kept under standard vivarium conditions at 20–24°C with a 12-hour light cycle and access to water and food ad libitum.

Animals were allocated to groups using the block randomization method. A larger number of rats were assigned to the combined toxin administration group due to expected increased mortality resulting from toxin exposure; however, no animal deaths occurred during this study.

Surgical procedures have been described in detail previously [18]. Briefly, during stereotaxic surgery, bilateral ICV injections of LPS (Escherichia coli O55:B5 endotoxin, Sigma) at a concentration of 4 μg/μL (injection volume 5 μL) were performed according to the coordinates of a rat brain atlas [19]. Sham-operated animals received an equivalent volume of physiological saline (PS).

Three days after surgery, to induce ataxia, experimental animals received an IP injection of 3-AP solution at a dose of 40 mg/kg (injection volume 0.3 mL). Control animals received an equivalent volume of PS via the same route.

Thus, the animals were divided into 4 groups:

• Control (n = 7) – sham-operated animals receiving IP PS;
• LPS+PS (n = 7) – animals receiving ICV LPS and IP PS;
• PS+3-AP (n = 7) – sham-operated animals receiving IP 3-AP;
• LPS+3-AP (n = 9) – animals receiving ICV LPS and IP 3-AP.

During the experiment, animal body weight was regularly measured to monitor physical condition and recovery after the interventions.

At 1, 3, 6, and 9 days after 3-AP administration, the animals were tested in the Open Field (OF) test to assess general locomotor activity over a 3-minute period. Concurrently, the severity of neurological deficits was assessed using an adapted scale originally developed for a model of cerebellar stroke [20]. The original scale includes a series of measures assessing motor function, coordination, and postural responses. Each measure was scored according to established criteria, after which a total neurological score reflecting the degree of functional impairment was calculated (Table 1).

 

Table 1. Adapted scale for assessing the severity of ataxia in the Open Field test

Parameter	Score
	0	1	2	3	4
Spontaneous activity	Animal approaches 3–4 walls of the field and rears	Animal approaches 3–4 walls of the field and does not rear	Animal approaches 2 walls of the field and does not rear	Animal approaches 1 wall of the field or goes into a corner, no rearing	Animal does not move away from its starting position
Walking	Animal is capable of rapid movement; forelimb and hindlimb movements are coordinated	Animal moves slowly; forelimb and hindlimb movements are coordinated	Animal moves slowly; asynchrony between forelimb and hindlimb movements is observed	Animal moves in a jerky/rolling manner most of the time	Animal barely moves
Balance during walking	Animal easily changes postures	Animal sways while walking	Animal loses balance while walking (turns over, stumbles, falls onto its side) Note: frequent balance losses during the 1st minute of the test are not counted	Animal lacks the ability to maintain balance while walking	Animal barely moves
Hindlimb placement	Normal position of both limbs	Minor placement abnormalities (e.g., one limb placed outward, without significant effect on gait and balance)	Slight bilateral abnormalities	Gross abnormalities (limbs splayed outward) Note: pronounced limb deviations from normal position during the 1st minute of the test are not counted	–
Forelimb placement	Normal position of both limbs	Minor placement abnormalities (e.g., one limb placed outward, without significant effect on gait and balance)	Slight bilateral abnormalities	Gross abnormalities (limbs splayed outward) Note: pronounced limb deviations from normal position during the 1st minute of the test are not counted	–
Backing up, sideways movement	None	Rare (1–3 episodes during the observation period)	Frequent (> 3 episodes during the observation period)	–	–
Loss of balance during grooming or while stationary standing	None	Rare (1–3 episodes during the observation period)	Frequent (> 3 episodes during the observation period)	Animal cannot stand on its paws	–
Action tremor	None	Slight tremor, mildly affecting the animal’s movement	Present; significantly impairs the animal’s movement	–	–
Wall support	None	Rare (1–3 episodes during the observation period or total duration <1/3 of test time)	Frequent (> 3 episodes during the observation period or > 1/3 of test time)	After touching a wall, the animal does not move away from it	–
Tail wagging	None	Rare (1–3 episodes during the observation period)	Frequent (> 3 episodes during the observation period)	–	–

 

Subsequent behavioral testing was aimed at assessing impairments in motor coordination and balance and included the Rung ladder test (RLT; 3 min) and the Beam-Walking Test (BWT; 100 s) [21]. The following parameters were evaluated: number of foot slips and traversal time (BWT), number of correct paw placements on rungs, number of slips, Skilled walking performance score (SWPS) [22], and test completion time (RLT).

Upon completion of the physiological study, the animals were decapitated, and their brains were fixed in 4% formalin. 10 μm sections were prepared using a Tissue-Tek Cryo3 Flex cryostat (Sakura FineTek), and target protein staining was performed according to standard protocols. To identify Purkinje cells, anti-aldolase C antibodies (AldC) (1:150, PA-12317, ThermoFisher) were used; to identify microglia, anti-IBA1 antibodies (1:400, ab178847, Abcam) were used. For immunofluorescence detection, appropriate secondary anti-rabbit IgG antibodies labeled with the fluorochrome Alexa Fluor 488 (1:300; a21206, ThermoFisher) were employed, following the manufacturers’ recommended protocols. The sections were then mounted in FluoroShield medium containing the fluorochrome DAPI for nuclear staining. Qualitative assessment of the developing cerebellar alterations was performed on images obtained using microscopes (Nikon SMZ-18, Nikon Eclipse Ni-e).

Investigators were blinded during randomization, animal care and veterinary monitoring, behavioral data recording, and immunohistochemical analysis (researchers and technicians were not informed of the animals’ group allocation). To this end, cage labels, animals, and tissue samples were pre-coded by assigning random identification numbers. Blinding did not apply to study planning, surgical interventions, drug administration, or statistical data processing. The absence of an a priori preferential hypothesis reduced the risk of systematic bias and eliminated potential conflicts of interest.

Statistical analysis was performed using the Prism 10.3.1 software package (GraphPad Software, Inc.). Normality of the distribution was assessed using the Shapiro–Wilk test. For data with a normal distribution, one-way analysis of variance (ANOVA) was applied; for data deviating from normality, the Kruskal–Wallis test was used. Due to the lack of an adequate non-parametric alternative for repeated-measures data, two-way repeated-measures ANOVA was employed. Residuals were additionally checked for normality using the Shapiro–Wilk test. To mitigate the risk of violating the sphericity assumption, the Greenhouse–Geisser correction was applied. Multiple comparisons were performed using Dunnett’s correction. Differences were considered statistically significant at p < 0.05.

Results

Analysis of body weight changes showed that on postoperative days 5, 7, 10, and 14, animals in the LPS+3-AP group exhibited a significant reduction in body weight compared to the control group (on day 14: 95% CI 39.01–124.70). In animals receiving 3-AP alone, a significant reduction was observed from day 7 to day 14 (on day 14: 95% CI 3.079–95.590). No differences in body weight were found between the control group and animals receiving LPS alone at any time point (Fig. 1).

 

Fig. 1. Changes in animal body weight following ICV administration of LPS and subsequent IP administration of 3-AP.

Data are presented as mean ± standard error of the mean. *p < 0.05 compared to the control group.

 

In the OF test, on day 1 after 3-AP administration, animals in the LPS+3-AP group showed a statistically significant reduction in total distance traveled (95% CI 2.283–11.140; Fig. 2, A) and in total turn angle (95% CI 436.7–2980.0; Fig. 2, B) compared to the control group. By day 3, a trend toward a reduction in these parameters persisted. In the 3-AP group, a significant reduction in total distance traveled (95% CI 1.576–11.45; Fig. 2, A) and a trend toward a decrease in total turn angle (Fig. 2, B) were observed on day 1 compared to controls. The adapted neurological deficit scale revealed the most pronounced changes in the LPS+3-AP group at all time points, with a significant worsening compared to controls (on day 1 of testing: 95% CI –22.87 to –2.126; Fig. 2, C). In the PS+3-AP group, a significant worsening was observed on day 1 (95% CI –9.450 to –0.5502), with a trend toward improvement on subsequent days. In the LPS+PS group, only trend-level changes were observed (Fig. 2, D).

 

Fig. 2. Effect of ICV administration of LPS and subsequent IP administration of 3-AP on rat behavior in the OF.

*p < 0.05, ^§p < 0.1 compared to the control group.

Data are presented as mean ± standard error of the mean.

 

In the RLT, a significant decrease in forelimb SWPS was observed in animals with the combined ataxia model compared to controls (95% CI 0.0114–0.2090; Fig. 3, A). A decrease in hindlimb SWPS was observed both in animals of the 3-AP group and under combined exposure (LPS+3-AP) (95% CI 0.0216–0.3100 and 95% CI 0.0715–0.3390, respectively; Fig. 3, B). In rats in the LPS group, a tendency toward an increased latency to begin moving along the ladder was noted relative to controls (Fig. 3, C). Animals receiving 3-AP alone showed a tendency toward increased test completion time, while under combined exposure (LPS+3-AP), this parameter was significantly increased compared to the control group (95% CI –92.3 to –21.4; Fig. 3, D).

 

Fig. 3. Effect of ICV administration of LPS and subsequent IP administration of 3-AP on rat behavior in the RLT.

Data are presented as mean ± standard error of the mean.

 

In the BWT, only 75% of animals in the 3-AP group and 50% of animals in the combined model group reached the dark chamber of the apparatus; however, the differences did not reach statistical significance (Fisher’s exact test, p > 0.05; Fig. 4). Evaluation of subsequent parameters was performed only among animals that reached the dark chamber. Among these, animals in the PS+3-AP and LPS+3-AP groups showed a significant increase in the total number of foot slips compared to the control group (95% CI –16.7 to –0.609 and 95% CI –17.7 to –1.61, respectively; Fig. 4, A). In addition, animals in the combined model group (LPS+3-AP) showed a significant increase in test traversal time (95% CI –102 to –9.81; Fig. 4, B).

 

Fig. 4. Effect of ICV administration of LPS and subsequent IP administration of 3-AP on rat behavior in the BWT.

Data are presented as mean ± standard error of the mean.

 

Qualitative morphological examination revealed rarefaction of the ganglionic layer in the groups of animals receiving 3-AP, including edema, pyknosis, and neuronal hyperchromasia. A decrease in immunoreactivity for AldC (zebrin II), a marker protein for a subpopulation of Purkinje cells, was observed. These changes were seen in both the cerebellar hemispheres and the vermis. Microglial staining under 3-AP alone revealed microglial activation in the cerebellar white matter, with elongated microgliocytes with shortened processes predominating. In the group receiving combined 3-AP and LPS administration, reactive microglial changes were more pronounced: amoeboid forms of microglia and occasional macrophages were identified, particularly near the fourth ventricle.

Thus, combined exposure to LPS and 3-AP leads to more pronounced impairments compared to single-toxin administration, as manifested by reduced body weight, decreased locomotor activity, impaired coordination, and increased test completion times. Qualitative morphological analysis, performed on a limited number of micrographs, indicates dystrophic changes in Purkinje cells and microglial activation that are more pronounced with combined exposure, consistent with the observed behavioral impairments.

Discussion

Clinically, ataxia is characterized by impaired postural control and movement coordination. This typically manifests as an unstable, wide-based gait, reduced walking speed, decreased cadence and swing phase duration, prolonged double-support period, and increased variability in spatial and temporal gait parameters (particularly step length and width, as well as step cycle duration) [23].

 

Fig. 5. Morphological changes in the cerebellum induced by ICV administration of LPS and subsequent IP administration of 3-AP in rats.

A–C — Nissl staining, ×25 (fragments of cerebellar hemispheres); D–F — immunostaining for the Purkinje cell marker protein AldC, ×10 (fragments of cerebellar vermis); G–I — immunostaining for the microglial marker protein IBA1, ×40 (fragments of cerebellar hemispheres). Mo — molecular layer; Gn — ganglionic layer; Gr — granular layer; WM — cerebellar white matter.

 

Since SCA has a hereditary basis, the generation of genetic disease models is an important research direction. However, the ataxic phenotype can also be reproduced in toxin-induced models. It should be noted that the development and maintenance of genetic models require sophisticated technologies and considerable financial resources, and the dynamics of phenotype formation in such models may not fully correspond to disease progression in humans. Therefore, toxic models of ataxia are also widely used in experimental studies. Among the most frequently used are models based on the administration of 3-AP, ethanol, cytosine arabinoside, and others (Table 2) [9].

 

Table 2. Single-toxin models used to reproduce the ataxic phenotype in rodents

Toxin	Mechanisms of action	Advantages	Limitations	Sources
3-AP	NAD+ depletion; neuronal death in the inferior olivary nuclei; loss of climbing fibers	Rapidly developing and highly reproducible ataxic phenotype	Acute nature of injury; does not replicate the progressive course of SCA	[24]
Harmaline	Desynchronization of inferior olivary neurons; arrhythmic neuronal activity	Involvement of olivocerebellar circuitry	Primarily used to study essential tremor	[25]
LPS	Induction of innate immune response; activation of microglia and astroglia	Enables study of neuroinflammation’s contribution to ataxia pathogenesis	Primarily reproduces the inflammatory component of cerebellar injury	[26]
Ethanol	Disruption of synaptic transmission in the cerebellum; oxidative stress; epigenetic changes	Ease of induction; high reproducibility of ataxic phenotype	Reversibility with acute administration; lack of selective action	[27]
Cytosine arabinoside (cytarabine)	Incorporation of Ara-CTP into DNA; death of proliferating granule cells; secondary Purkinje cell degeneration	Development of persistent ataxic phenotype; reduced cerebellar volume and neuron number	Requires neonatal administration; toxicity	[28]
Ibogaine	Astrocytosis; damage to climbing fibers and Purkinje cells	Dose-dependent motor impairments (tremor, ataxia)	Neurotoxicity and cardiotoxicity	[24, 29]
Mefloquine	Blockade of Cx36 channels in inferior olivary neurons; oxidative stress; disruption of calcium homeostasis	Pharmacological effects are reversible and temporary; neuronal death in brainstem nuclei	Low selectivity; absence of typical neurodegeneration	[30, 31]
Acrylamide	Binds to glutathione and thioredoxin, provoking oxidative stress; binds to DNA and hemoglobin; disrupts SNARE/NSF function; activation of nuclear transcription factor NF-κB	Purkinje cell death; distal fiber degeneration in the cerebellum and brainstem; reduced catecholamine levels; α-syn accumulation; motor impairments	Nonspecific neurotoxicity (cerebrum, peripheral nerves); general toxicity (kidneys, liver, testes)	[32, 33]
Artemisinin	Formation of free radicals from the endoperoxide group and alkylation of cellular proteins, leading to neuronal damage, necrosis, chromatolysis, and gliosis	Affected brain structures are clearly defined: red nucleus, superior olive, trapezoid body, and inferior vestibular nuclei	Often, but not always, accompanied by behavioral manifestations of toxicity. Primarily affects the brainstem rather than the cerebellar cortex	[34]
D-galactose	Oxidative stress, apoptosis, reduced levels of brain-derived neurotrophic factor and glutathione, protein and DNA damage	Rapid development of motor impairments; widely used to evaluate neuroprotective and antioxidant compounds	D-galactose induces neurodegeneration in various brain regions (hippocampus, cortex, brainstem), not exclusively in cerebellar Purkinje cells	[35, 36]
Streptozotocin (ICV)	Provokes oxidative stress; alkylating agent; enhances accumulation of aberrant protein forms	Increased intercellular distance in the Purkinje cell layer	Model primarily mimics Alzheimer’s disease rather than ataxia; nonspecific brain damage	[37]
Streptozotocin (IP)	Elevated levels of proinflammatory cytokines (TNF-α, IL-6, MCP-1); impaired autophagic activity; Purkinje cell loss	Reproducible neurodegeneration of Purkinje cells and granule neurons	Secondary ataxia due to diabetic neuropathy; not a direct model of SCA	[38]

 

Despite their widespread use, single-toxin models have a number of limitations. As shown in Table 2, they predominantly reproduce individual components of the disease, whereas the neurodegenerative processes underlying SCA are characterized by a complex and multifactorial pathogenesis involving neuroinflammatory, metabolic, and synaptic changes. In this regard, increasing attention is being devoted to combined experimental models based on the multiple-hit hypothesis [39].

Previously, we established that administration of 3-AP at a dose of 67 mg/kg induces severe locomotor disturbances (astasia and abasia); therefore, a lower dose of the neurotoxin was used in the present study to reproduce moderate behavioral impairments [40].

Experimental models have shown that transient microglial activation, such as occurs during systemic inflammation, can lead to glial priming, in which microglia adopt a less protective, neurotoxic phenotype that exhibits heightened reactivity to subsequent damaging factors. As a result, a secondary insult produces more pronounced neuroinflammation and neuronal damage compared to either factor alone. An illustrative example is the study by S.T. Xie et al., in which the authors demonstrated that chemogenetic activation of microglia exacerbates the severity of 3-AP-induced ataxia [16]. In particular, they observed significant worsening of motor coordination and decreased locomotor activity. In our study, sequential exposure to LPS and 3-AP was accompanied by more pronounced body weight loss, hypolocomotion (manifested as reduced overall locomotor activity), and increased test completion times. These results suggest a possible sensitizing effect of neuroinflammation on subsequent toxic damage to the cerebellum. In addition, impaired SWPS was observed in both the forelimbs and hindlimbs. An adapted scale allowed detection of more subtle changes in neurological deficits compared to traditional behavioral parameters, and these differences persisted until the end of the observation period, underscoring its value for future studies [16, 41].

Purkinje cell loss is considered one of the key morphological hallmarks associated with ataxic phenotype. However, it has been shown that in several experimental models, motor coordination impairments arise even before significant cerebellar neurodegeneration and neuronal loss, indicating the importance of early Purkinje cell dysfunction in the pathogenesis of ataxia [42–44].

In our study, the observed rarefaction of the ganglionic layer and decreased AldC immunoreactivity also indicate damage to Purkinje cells, which is consistent with the ataxic phenotype observed in the animals. It is also known that systemic administration of 3-AP is accompanied by neuroinflammation, as confirmed by morphological changes in microglia, increased expression of CD11b and pro-inflammatory cytokines (interleukin-1β, tumor necrosis factor-α), as well as decreased levels of neurotrophic factors such as IGF-1. In this regard, microglial activation following both 3-AP administration and combined toxin exposure appears to be an expected phenomenon [45].

The complex and stage-dependent role of neuroinflammation should be noted. For example, astrocyte-specific inhibition of the NF-κB signaling pathway in an SCA model has been shown to exert a bidirectional effect: its suppression at early stages exacerbates disease progression, while at late stages it improves motor function. Moreover, both ICV and systemic administration of LPS alone can induce temporary motor impairments in rodents. However, in our study, a single ICV injection of LPS was associated only with an increased latency to initiate movement in the ladder beam walking test, whereas no significant differences were detected in other tests [46, 47].

Finally, it is important to emphasize the transient nature of the motor impairments in the model used. The peak severity of motor impairments was observed 24 hours after 3-AP administration. At subsequent time points, partial functional compensation was observed, the degree of which varied among animals and likely reflected individual differences in the nervous system’s adaptation to induced neurodegenerative damage.

Limitations of the study. Due to the transient nature of the motor impairments, this model limits the possibility of directly extrapolating the obtained results to progressive forms of SCA in humans, a factor that should be considered when planning future studies. The small sample size (n = 7–9 per group) is consistent with several similar studies but may reduce statistical power and limit the detection of more subtle effects. Furthermore, the absence of quantitative morphological analysis does not allow full characterization of the observed structural changes.

Conclusion

Combined exposure to LPS and 3-AP reproduces a more pronounced SCA phenotype, manifested by impaired motor coordination and locomotion, reduced numbers of AldC-positive neurons, and microglial activation in the cerebellum. These findings indicate a possible sensitizing role of neuroinflammation and support the use of this model for further investigation of this process.

About the authors

Andrei A. Gerasimov

Russian Center of Neurology and Neurosciences

Email: drewgerasimov@gmail.com
ORCID iD: 0009-0001-6853-4143

junior researcher, Laboratory of experimental pathology of nervous system and neuropharmacology, Brain Institute

Russian Federation, Moscow

Dmitry N. Voronkov

Russian Center of Neurology and Neurosciences

Email: voronkov@neurology.ru
ORCID iD: 0000-0001-5222-5322

Cand. Sci. (Med.), senior researcher, Laboratory of neuromorphology, Brain Institute

Russian Federation, Moscow

Ivan A. Potapov

Russian Center of Neurology and Neurosciences

Email: alla_stav@mail.ru
ORCID iD: 0000-0002-7471-3738

junior researcher, Laboratory of experimental pathology of nervous system and neuropharmacology, Brain Institute

Russian Federation, Moscow

Anastasia K. Pavlova

Russian Center of Neurology and Neurosciences

Email: pav_nastasya@mail.ru
ORCID iD: 0009-0006-5653-5524

research assistant, Laboratory of experimental pathology of nervous system and neuropharmacology, Brain Institute

Russian Federation, Moscow

Alla V. Stavrovskaya

Russian Center of Neurology and Neurosciences

Author for correspondence.
Email: alla_stav@mail.ru
ORCID iD: 0000-0002-8689-0934

Cand. Sci. (Biol.), Head, Laboratory of experimental pathology of nervous system and neuropharmacology Brain Institute

Russian Federation, Moscow

Sergey N. Illarioshkin

Russian Center of Neurology and Neurosciences

Email: marat.muhamedyarov@kazangmu.ru
ORCID iD: 0000-0002-2704-6282

Dr. Sci. (Med.), Prof., Full member of the RAS, Director, Brain Institute, Deputy director

Russian Federation, Moscow

References

Supplementary files