Sex steroid hormones in depressive disorders as a basis for new potential treatment strategies.

The sex steroid hormones (SSHs) such as testosterone, estradiol, progesterone, and their metabolites have important organizational and activational impacts on the brain during critical periods of brain development and in adulthood. A variety of slow and rapid mechanisms mediate both organizational and activational processes via intracellular or membrane receptors for SSHs. Physiological concentrations and distribution of SSHs in the brain result in normal brain development.

Molecular actions of sex hormones in the brain and their potential treatment use in anxiety disorders.

Anxiety disorders are one of the most prevalent mood disorders that can lead to impaired quality of life. Current treatment of anxiety disorders has various adverse effects, safety concerns, or restricted efficacy; therefore, novel therapeutic targets need to be studied. Sex steroid hormones (SSHs) play a crucial role in the formation of brain structures, including regions of the limbic system and prefrontal cortex during perinatal development.

On the role of sex steroids in biological functions by classical and non-classical pathways. An update.

The sex steroid hormones (SSHs) play several roles in regulation of various processes in the cardiovascular, immune, muscular and neural systems. SSHs affect prenatal and postnatal development of various brain structures, including regions associated with important physiological, behavioral, cognitive, and emotional functions. This action can be mediated by either intracellular or transmembrane receptors.

Neonatal hypoxic-ischemic brain injury leads to sex-specific deficits in rearing and climbing in adult mice.

The study examined the morphological and long-term behavioral impacts of neonatal hypoxic-ischemic brain injury in a mouse model. We investigated the modification of different behavioral domains, such as spontaneous climbing, which represents fine motor skills. We also focused on sex-dependent differences during hypoxic-ischemic encephalopathy.

Perinatal hypoxic-ischemic damage: review of the current treatment possibilities.

Neonatal hypoxic-ischemic encephalopathy is a disorder with heterogeneous manifestation due to asphyxia during perinatal period. It affects approximately 3-12 children per 1000 live births and cause death of 1 million neonates worldwide per year. Besides, motor disabilities, seizures, impaired muscle tone and epilepsy are few of the consequences of hypoxic-ischemic encephalopathy.

Lack of M muscarinic receptors in the striatum, thalamus and intergeniculate leaflet alters the biological rhythm of locomotor activity in mice.

The deletion of M muscarinic receptors (MRs) changes biological rhythm parameters in females. Here, we searched for the mechanisms responsible for these changes. We performed biological rhythm analysis in two experiments: in experiment 1, the mice [C57Bl/6NTac (WT) and M MR -/- mice (KO)] were first exposed to a standard LD regime (12/12-h light/dark cycle) for 8 days and then subsequently exposed to constant darkness (for 24 h/day, DD regime) for another 16 days.

Sex-related differences in locomotion and climbing of C57Bl/6NTac mice in a novel environment.

Laboratory mice in standard laboratory cages, besides horizontal and vertical locomotor activity, spontaneously display cage-bar related activities such as cage-grid climbing. Although, grid-climbing activity is one of the major components of spontaneous home-cage behavior of mice, its exact role is not fully understood. This study aimed to describe the sex-differences in coping with novelty and in spontaneous behavior of laboratory mice concerning the cage-climbing activity in an observer-independent open field test.

Gender differences involved in the pathophysiology of the perinatal hypoxic-ischemic damage.

Hypoxic-ischemic encephalopathy (HIE) is a neonatal condition that occurs as a consequence of perinatal asphyxia, which is caused by a number of factors, commonly via compression of the umbilical cord, placental abruption, severe meconium aspiration, congenital cardiac or pulmonary anomalies and birth trauma. Experimental studies have confirmed that male rat pups show a higher resistance to HIE treatment. Moreover, the long-term consequences of hypoxia in male are more severe in comparison to female rat pups.

Early postnatal hypoxia induces behavioral deficits but not morphological damage in the hippocampus in adolescent rats.

Hypoxia is one of the major pathological factors affecting brain function. The aim of the present study was to describe the effect of neonatal hypobaric hypoxia on the behavior of rats and to analyze its effect on hippocampal neurodegeneration. Hypobaric hypoxia at a simulated altitude of 9000 m was induced for one hour in neonatal rat pups (PND7 and PND9) of both sexes.

Variability in the Drug Response of M Muscarinic Receptor Knockout Mice During Day and Night Time.

Mice are nocturnal animals. Surprisingly, the majority of physiological/pharmacological studies are performed in the morning, i.e.

Pathophysiology of perinatal hypoxic-ischemic encephalopathy - biomarkers, animal models and treatment perspectives.

Hypoxic-ischemic encephalopathy (HIE) is one of the leading pediatric neurological conditions causing long-term disabilities and socio-economical burdens. Nearly 20-50 % of asphyxiated newborns with HIE die within the newborn period and another third will develop severe health consequences and permanent handicaps. HIE is the result of severe systemic oxygen deprivation and reduced cerebral blood flow, commonly occurring in full-term infants.

CT imaging and spontaneous behavior analysis after osmotic blood-brain barrier opening in Wistar rat.

In our previous experiments we demonstrated that osmotic opening of the blood brain barrier (BBB) in rats by administration of mannitol into the internal carotid artery leads to cerebral edema. The aim of this study was to confirm objectively the development of brain edema and determine whether it affects spontaneous locomotor activity in rats (SLA). Brain edema was verified by computer tomography (CT) examination of the brain and SLA was observed during open field test.

Influence of low-dose neonatal domoic acid on the spontaneous behavior of rats in early adulthood.

Consumption of seafood containing toxin domoic acid (DA) causes an alteration of glutamatergic signaling pathways and could lead to various signs of neurotoxicity in animals and humans. Neonatal treatment with domoic acid was suggested as valuable model of schizophrenia and epilepsy. We tested how repeated early postnatal DA administration influences the spontaneous behavior of rats in adulthood.

Subconvulsive dose of kainic acid transiently increases the locomotor activity of adult Wistar rats.

Kainic acid (KA) is a potent neurotoxic substance valuable in research of temporal lobe epilepsy. We tested how subconvulsive dose of KA influences spontaneous behavior of adult Wistar rats. Animals were treated with 5 mg/kg of KA and tested in Laboras open field test for one hour in order to evaluate various behavioral parameters.

Low dose domoic acid influences spontaneous behavior in adult rats.

Domoic acid (DA) is a potent marine neurotoxine present in seafood. Intoxication by DA causes gastrointestinal symptoms like vomiting and diarrhoea and also the so-called amnesic shellfish poisoning (inflicting memory impairment and seizures). Since exposure to non-convulsive doses is relevant to the human health, we investigated the effect of low dose DA administration in adult Wistar rats.

Both water intoxication and osmotic BBB disruption increase brain water content in rats.

Our previous experiments revealed that water intoxication and osmotic BBB disruption in the rat allow penetration of high-molecular substances into the brain and that resulting changes in the internal environment of the CNS lead to pathological development, such as the loss of integrity of myelin. The aim of the present study was to determine whether the previously described phenomena are associated with increased water content in the brain. To answer the question following methods were used: a) water intoxication: intraperitoneal administration of distilled water, b) osmotic BBB disruption: application of mannitol (20 %) selectively into the internal carotid artery, c) brain wet weight was measured after decapitation, and subsequently (after six days in thermostat set at 86 °C) the dry weight were estimated d) in animals with 20 % and 30 % hyperhydration the degree of myelin deterioration was estimated e) animal locomotor activity was tested by continuous behavior tracking and analysis.

Influence of allopurinol on evoked cortical afterdischarges during early ontogenesis.

The aim of our study was to test the hypothesis, whether repeated allopurinol pre-treatment (in dose of 135 mg/kg s.c.) can influence changes of brain excitability caused by long-term hypoxia exposition in young immature rats.

Ascorbic acid and alpha-tocopherol protect age-dependently from hypoxia-induced changes of cortical excitability in developing rats.

Objectives: The effects of ascorbic acid and α-tocopherol pre-treatment on hypoxia induced changes in brain cortex excitability were tested in immature rats exposed chronically to simulated altitude of 7 000 m.

Methods: Rat pups were kept together with their mothers for 8 hours a day in hypobaric chamber since the day of the birth till the postnatal day 11 or 17. Each day immediately before placing to hypobaric chamber pups were pretreated intraperitoneally either with ascorbic acid (100 mg/kg) or α-tocopherol (1 500 mg/kg).

Nicotine and kainic acid effects on cortical epileptic afterdischarges in immature rats.

Aim of the study was to test the effect of nicotine (NIC) and kainic acid (KA) co-treatment in immature rats. Male Wistar albino rats (two different age groups) were chosen for the study. Experiments started on postnatal day (PD) 8 or 21 and animals were treated twice a day for three days with nicotine, fourth day KA was administered.

Impact of chronic ethanol intake of rat mothers on the seizure susceptibility of their immature male offspring.

The aim of present study was to examine the impact of prenatal ethanol exposure on seizure susceptibility of the offspring. Pregnant Wistar rats were compelled to drink either 10% or 20% ethanol solution, as the only drinking fluid since conception up to the weaning of their offspring at the age of 28 days. Pregnant and nursing rats of the control group drank water.

Neuroprotective effect of nicotine against kainic acid excitotoxicity is associated with alpha-bungarotoxin insensitive receptors subtype of nAChRs.

Objectives: Our previous study showed that administration of nicotine is capable to protect the neurons of hippocampus against the kainic acid induced damage. Here we tested the hypotheses that multiple nicotine administration would prevent the effects of kainic acid on neuronal nicotinic receptor subtypes densities (α-bungarotoxin sensitive and α-bungarotoxin insentive) and on hippocampal cell degeneration.

Methods: Radioligand binding study was used to detect the particular nAChR subtypes densities.

Methylprednisolone reduces axonal impairment in the experimental model of brain oedema.

Objectives: In our earlier paper we demonstrated that opening of the blood-brain barrier with an osmotic insult induces brain oedema which represents a factor triggering axonal impairment accompanied with myelin disintegration. The aim of the present study was to find whether methylprednisolone can reduce such axonal impairment in our model of brain oedema.

Methods: Brain oedema was induced by osmotic blood-brain barrier opening with 20% mannitol applied selectively into the internal carotid.

Beta3 adrenoceptors substitute the role of M(2) muscarinic receptor in coping with cold stress in the heart: evidence from M(2)KO mice.

We investigated the role of beta3-adrenoceptors (AR) in cold stress (1 or 7 days in cold) in animals lacking main cardioinhibitive receptors-M2 muscarinic receptors (M(2)KO). There was no change in receptor number in the right ventricles. In the left ventricles, there was decrease in binding to all cardiostimulative receptors (beta1-, and beta2-AR) and increase in cardiodepressive receptors (beta3-AR) in unstressed KO in comparison to WT.

Nicotine reduces mortality of developing rats exposed to high-altitude hypoxia and partially suppresses the duration of cortical epileptic afterdischarges.

Nicotine has been repeatedly reported as substance possessing neuroprotective properties. This study focused on the possible beneficial effects of nicotine against the high-altitude hypoxia (9000 m for one hour). 15 min prior to hypoxia exposition rats (12- and 35-day-old) were treated with nicotine.

Is learning ability and spatial memory in rats influenced by single dose of nicotine?

A lot of studies have been concentrated on an effect of a short or a long-term administration of nicotine in humans or in animals. The negative effects on the human organism have been known for a long time, but these health problems are known especially from observing smokers. The number of tasks in human and in animals with accent on positive effect of nicotine has increased especially with regard to improvement of cognitive functions.