Abnormal Astrocyte Heterogeneity in the Dentate Gyrus of Rats Prone to Audiogenic Seizures Can Be Corrected by the Nootropic Drug Piracetam.

Accumulating evidence indicates that inherited astrocyte dysfunction can be a primary trigger for epilepsy development; however, the available data are rather limited. In addition, astrocytes are considered as a perspective target for the design of novel and improvement of the existing antiepileptic therapy. Piracetam and related nootropic drugs are widely used in the therapy of various epileptic disorders, but detailed mechanisms of racetams action and, in particular, their effects on glial functions are poorly understood.

Aging of Krushinsky-Molodkina audiogenic rats is accompanied with pronounced neurodegeneration and dysfunction of the glutamatergic system in the hippocampus.

Advancing age strongly correlates with an increased risk of epilepsy development. On the other hand, epilepsy may exacerbate the negative effects of aging making it pathological. In turn, the possible link between aging and epileptogenesis is dysregulation of glutamatergic transmission.

Audiogenic kindling activates glutamatergic system in the hippocampus of rats with genetic predisposition to audiogenic seizures.

Temporal lobe epilepsy (TLE) development is associated with dysregulation of glutamatergic transmission in the hippocampus; however, detailed molecular mechanisms of pathological changes are still poorly understood. In the present study, we performed the complex analysis of glutamatergic system in the hippocampus of Krushinsky-Molodkina (KM) rats genetically prone to audiogenic seizures (AGS). Daily AGS stimulations (audiogenic kindling) were used to reproduce the dynamics of TLE development.

In search of stress: analysis of stress-related markers in mice after hindlimb unloading and social isolation.

Objectives: Hindlimb unloading (HU), widely used to simulate microgravity effects, is known to induce a stress response. However, as single-housed animals are usually used in such experiments, social isolation (SI) stress can affect experimental results. In the present study, we aimed to delineate stressful effects of 3-day HU and SI in mice.

Short-term hindlimb unloading negatively affects dopaminergic transmission in the nigrostriatal system of mice.

The nigrostriatal system composed of the dorsal striatum and the substantia nigra (SN) is highly involved in the control of motor behavior. Various extremal and pathological conditions as well as social isolation (SI) may cause an impairment of locomotor function; however, corresponding alterations in the nigrostriatal dopaminergic pathway are far from full understanding. Here, we analyzed the effect of 3-day hindlimb unloading (HU) and SI on the key players of dopamine transmission in the nigrostriatal system of CD1 mice.

Dynamics of neurodegeneration in the hippocampus of Krushinsky-Molodkina rats correlates with the progression of limbic seizures.

Audiogenic seizures (AGS) (audiogenic kindling) in genetically selected audiogenic rodents are a reliable model of temporal lobe epilepsy (TLE). Temporal lobe epilepsy is accompanied with neurodegeneration in the hippocampus, but how the cells die is not fully understood. We analyzed the dynamics and mechanisms of cell loss in the hippocampus of audiogenic Krushinsky-Molodkina (KM) rats during the development of TLE.

Audiogenic kindling stimulates aberrant neurogenesis, synaptopodin expression, and mossy fiber sprouting in the hippocampus of rats genetically prone to audiogenic seizures.

Temporal lobe epilepsy is associated with considerable structural changes in the hippocampus. Pharmacological and electrical models of temporal lobe epilepsy in animals strongly suggest that hippocampal reorganization is based on seizure-stimulated aberrant neurogenesis but the data are often controversial and hard to interpret. The aim of the present study was to estimate neurogenesis and synaptic remodeling in the hippocampus of Krushinsky-Molodkina (KM) rats genetically prone to audiogenic seizures (AGS).

Prochlorperazine Withdraws the Delayed Onset Tonic Activity of Unloaded Rat Soleus Muscle: A Pilot Study.

A gradual increase in rat soleus muscle electromyographic (EMG) activity is known to occur after 3-4 days of hindlimb suspension/unloading (HS). The physiological significance and mechanisms of such activity of motoneurons under unloading conditions are currently unclear. Since hyperactivity of motoneurons and muscle spasticity after spinal cord injury are associated with KCC2 downregulation, we hypothesized that a decrease in potassium (K)/chloride (Cl) co-transporter 2 (KCC2) in motoneurons would be responsible for an increase in soleus muscle EMG activity during HS.

Plantar Stimulations during 3-Day Hindlimb Unloading Prevent Loss of Neural Progenitors and Maintain ERK1/2 Activity in the Rat Hippocampus.

Adult neurogenesis is a flexible process that depends on the environment and correlates with cognitive functions. Cognitive functions are impaired by various factors including space flight conditions and reduced physical activity. Physically active life significantly improves both cognition and the hippocampal neurogenesis.

Impaired postnatal development of the hippocampus of Krushinsky-Molodkina rats genetically prone to audiogenic seizures.

The hippocampus plays an important role in epilepsy progression even if it is not involved in seizure generalization. We hypothesized that abnormal development of the hippocampus may underlie epileptogenesis. Here we analyzed postnatal development of the hippocampus of Krushinsky-Molodkina (KM) rats, which are the animal model of reflex audiogenic epilepsy.

Dynamic Foot Stimulations During Short-Term Hindlimb Unloading Prevent Dysregulation of the Neurotransmission in the Hippocampus of Rats.

Spaceflight and simulated microgravity both affect learning and memory, which are mostly controlled by the hippocampus. However, data about molecular alterations in the hippocampus in real or simulated microgravity conditions are limited. Adult Wistar rats were recruited in the experiments.

Glutamatergic Fate of Neural Progenitor Cells of Rats with Inherited Audiogenic Epilepsy.

Epilepsy is associated with aberrant neurogenesis in the hippocampus and may underlie the development of hereditary epilepsy. In the present study, we analyzed the differentiation fate of neural progenitor cells (NPC), which were isolated from the hippocampus of embryos of Krushinsky-Molodkina (KM) rats genetically prone to audiogenic epilepsy. NPCs from embryos of Wistar rats were used as the control.

Audiogenic kindling activates expression of vasopressin in the hypothalamus of Krushinsky-Molodkina rats genetically prone to reflex epilepsy.

The present study analysed the effects of audiogenic kindling on the functional state of the vasopressinergic system of Krushinsky-Molodkina (KM) rats. KM rats represent a genetic model of audiogenic reflex epilepsy. Multiple audiogenic seizures in KM rats lead to the involvement of the limbic structures and neocortex in the epileptic network.

Delayed audiogenic seizure development in a genetic rat model is associated with overactivation of ERK1/2 and disturbances in glutamatergic signaling.

Krushinsky-Molodkina (KM) rats genetically prone to audiogenic seizure are characterized by age-dependent expression of audiogenic seizures (AGS). It is known that the critical period of enhanced seizure susceptibility in rodents occurs at 2nd-3rd weeks of postnatal development. However, KM rats do not express AGS at this time-point, but start to demonstrate a stable AGS only after the age of 3 months.

Apoptosis and proliferation in the inferior colliculus during postnatal development and epileptogenesis in audiogenic Krushinsky-Molodkina rats.

It is known that audiogenic seizure (AGS) expression is based on the activation of the midbrain structures such as the inferior colliculus (IC). It was demonstrated that excessive sound exposure during the postnatal developments of the IC in rats led to AGS susceptibility in adulthood, which correlated with underdevelopment of the IC. In adult rodents, noise overstimulation induced apoptosis in the IC.

Effects of ERK1/2 kinases inactivation on the nigrostriatal system of Krushinsky-Molodkina rats genetically prone to audiogenic seizures.

Unlabelled: Recently, we demonstrated that inhibition of ERK1/2 activity by SL-327 treatment blocks seizure behavior in Krushinsky-Molodkina (KM) rats, which was mediated by altering of GABA and glutamate release mechanism in the hippocampus. Basal ganglia representing various subcortical cell groups play a significant role in the regulation of motor activity, including epileptiform seizures.

Objectives:  To verify if nigrostriatal system could be also affected by SL-327 treatment we analyzed the expression of tyrosine hydroxylase, D1 and D2 dopamine receptors, NR2B subunit of NMDA receptor as well as vesicular glutamate transporter VGLUT2 and glutamic acid decarboxylases GAD65/67 in the striatum and substantia nigra of KM rats.

The expression and distribution of seizure-related and synaptic proteins in the insular cortex of rats genetically prone to audiogenic seizures.

It is known that perirhinal/insular cortices participate in the transmission of sensory stimuli to the motor cortex, thus coordinating motor activity during seizures. In the present study we analysed seizure-related proteins, such as GABA, glutamate, ERK1/2 and the synaptic proteins in the insular cortex of Krushinsky-Molodkina (KM) rats genetically prone to audiogenic seizures (AGS). We compared seizure-naïve and seizure-experienced KM rats with control Wistar rats in order to distinguish whether seizure-related protein changes are associated with seizure event or representing an inhered pathological abnormality that determines predisposition to AGS.

Neurogenic potential of spinal cord organotypic culture.

There are several neurogenic niches in the adult mammalian central nervous system. In the central nervous system, neural stem cells (NSC) localize not only to the periventricular area, but are also diffusely distributed in the parenchyma. Here, we assessed neurogenic potential of organotypic cultures prepared from adult mouse spinal cord.

Inhibition of ERK1/2 signaling prevents epileptiform behavior in rats prone to audiogenic seizures.

It has recently been proposed that extracellular signal-regulated kinases 1 and 2 (ERK1/2) are one of the factors mediating seizure development. We hypothesized that inhibition of ERK1/2 activity could prevent audiogenic seizures by altering GABA and glutamate release mechanisms. Krushinsky-Molodkina rats, genetically prone to audiogenic seizure, were recruited in the experiments.

Effects of selective Bcl-2 inhibitor HA14-1 treatments on functional activity of magnocellular vasopressinergic neurons of rat hypothalamus.

In this study we examined whether in vivo treatments with Bcl-2 inhibitor HA14-1 can affect the function of vasopressinergic system of rat. HA14-1 is a novel organic compound that has micromolar affinity for Bcl-2 and Bcl-xL and acts as a mimetic of BH3-only proteins by antagonizing the anti-apoptotic Bcl-2 proteins and triggering Bax-dependent apoptosis. We found that intrahypothalamic injections of HA14-1 did not induce apoptosis of vasopressin (VP) cells of supraoptic nucleus, but led to activation of VP synthesis and release, resulting in decreased diuresis.

Apoptotic signaling proteins: possible participation in the regulation of vasopressin and catecholamines biosynthesis in the hypothalamus.

The role of apoptotic signaling proteins for long-lived neurons in the mature brain is poorly understood. Recently, we have shown that water deprivation leads to the activation of vasopressin (VP) secretion and expression of Bcl-2 and caspase-9 apototic proteins in the hypothalamus of the rat brain. In the present work, we continued to study a possible relationship between the functional activity of neurosecretory cells of the hypothalamus and apoptosis related proteins.